New benzothiazole based copper(II) hydrazone Schiff base complexes for selective and environmentally friendly oxidation of benzylic alcohols: The importance of the bimetallic species tuned by the choice of the counterion

Article abstract of DOI:10.1016/j.molliq.2020.112590

Green and sustainable chemistry approaches necessitate an ongoing investigation towards new, environmentally benign and selective catalysts. We have thus prepared a new benzothiazole-scaffolded hydrazone Schiff base ligand L and coordinated it with copper(II) ions leading to five different complexes, the form of which in the solid state is counterion-dependent. Nitrate, chloride and triflate anions lead to monometallic species, whereas utilization of sulfates and tetrafluoroborates is responsible for the formation of bimetallic assemblies. The catalytic efficiency of synthesized compounds was shown in Cu-TEMPO (2,2,6,6-tetramethyl-l-piperidinoxyl) aerobic oxidation of activated alcohols resulting in good to excellent conversions and 100% selectivity to form the corresponding aldehydes. Considering the experimental results and Density Functional Theory calculations we propose two most plausible reaction mechanisms that further corroborate the enhanced activity of bimetallic species. It appears that the tridentate character of the ligand sacrifices some of the overall catalytic efficiency for the selectivity of the process. Aqueous reaction medium, low catalyst loading, air as oxidant and exclusive oxidative selectivity render these Cu^II complexes promising candidates for further improvement.

Full text of DOI:10.1016/j.molliq.2020.112590

Journal Pre-proof
New benzothiazole based copper(II) hydrazone Schiff base
complexes for selective and environmentally friendly oxidation of
benzylic alcohols: The importance of the bimetallic species tuned
by the choice of the counterion
Aleksandra Bocian, Adam Gorczyński, Damian Marcinkowski,
Samanta Witomska, Maciej Kubicki, Paulina Mech, Małgorzata
Bogunia, Jakub Brzeski, Mariusz Makowski, Piotr Pawluć,
Violetta Patroniak
PII:
S0167-7322(19)36654-1
DOI:
https://doi.org/10.1016/j.molliq.2020.112590
MOLLIQ 112590
Reference:
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
4 December 2019
20 January 2020
26 January 2020
Please cite this article as: A. Bocian, A. Gorczyński, D. Marcinkowski, et al., New
benzothiazole based copper(II) hydrazone Schiff base complexes for selective and
environmentally friendly oxidation of benzylic alcohols: The importance of the bimetallic
species tuned by the choice of the counterion, Journal of Molecular Liquids(2018),
https://doi.org/10.1016/j.molliq.2020.112590
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New benzothiazole based copper(II) hydrazone Schiff base complexes for
selective and environmentally friendly oxidation of benzylic alcohols: the
importance of the bimetallic species tuned by the choice of the counterion
#
,1
#,*,1
2
1,3
Aleksandra Bocian , Adam Gorczyński , Damian Marcinkowski , Samanta Witomska ,
1
&,4
&,4
&,4
Maciej Kubicki , Paulina Mech , Małgorzata Bogunia , Jakub Brzeski , Mariusz
Makowski , Piotr Pawluć , Violetta Patroniak*
4
1,2
,1
*
corresponding author: violapat@amu.edu.pl, adam.gorczynski@amu.edu.pl
equal contribution of authors; & equal contribution of authors
#
1
Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614
Poznań, Poland
2
Wroclaw University of Economics, Komandorska 118/120, 53-345 Wroclaw, Poland
3
Wielkopolska Center for Advanced Technologies, Uniwersytetu Poznańskiego 10, 61-614
Poznań, Poland
4
Faculty of Chemistry, Department of Bioinorganic Chemistry, University of Gdańsk, W.
Stwosza 63, 80-308 Gdańsk, Poland
Abstract
Green and sustainable chemistry approaches necessitate an ongoing investigation towards new,
environmentally benign and selective catalysts. We have thus prepared a new benzothiazole-scaffolded
hydrazone Schiff base ligand L and coordinated it with copper(II) ions leading to five different
complexes, the form of which in the solid state is counterion-dependent. Nitrate, chloride and triflate
anions lead to monometallic species, whereas utilization of sulfates and tetrafluoroborates is
responsible for the formation of bimetallic assemblies. The catalytic efficiency of synthesized
compounds was shown in Cu-TEMPO (2,2,6,6-tetramethyl-l-piperidinoxyl) aerobic oxidation of
activated alcohols resulting in good to excellent conversions and 100% selectivity to form the
corresponding aldehydes. Considering the experimental results and Density Functional Theory
calculations we propose two most plausible reaction mechanisms that further corroborate the
enhanced activity of bimetallic species. It appears that the tridentate character of the ligand
sacrifices some of the overall catalytic efficiency for the selectivity of the process. Aqueous
reaction medium, low catalyst loading, air as oxidant and exclusive oxidative selectivity render
II
these Cu complexes promising candidates for further improvement.
Keywords: Copper; Coordination compounds; Complexes; Schiff base; Hydrazone; Alcohol
oxidation; Density Functional Theory (DFT); Green Chemistry; Environmental chemistry
1
. Introduction

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Selective transformation of alcohols into their carbonyl derivatives without their over-oxidation is
a challenging task that remains of significant importance due to the widespread application of
those products in many industrial processes. [1-3] Though there exists a variety of oxidation
methods [4-6] bearing in mind the necessity to implement sustainable, green chemistry
approaches [7], most of the currently applied oxidants fail to meet those standards. Utilization of
stoichiometric amounts followed by formation of hazardous and toxic byproducts rendered
environmentally benign species such as H O and O a viable alternatives. [8] One of the
2
2
2
intensively studied protocol for such a process involves a copper(I/II)-TEMPO (2,2,6,6-
tetramethyl-l-piperidinoxyl) system[9,10], which allows one to use catalytic amounts of
,
substrates. [11-13] Since the first processes reported by Semmelhack in 1983 and 1984, [14] [15]
the latter of which used CuCl/TEMPO system in DMF, lots of improvements were made [16-22],
I/II
which clearly showed that Cu oxidation state, solvent as well as basic additives could
significantly affect the catalytic process. [23] One of the most efficient and promising up-to-date
systems include [Cu(MeCN) ]OTf as the source of the metallic centre, bpy (2,2’-bipyridine)
4
ligand and NMI (N-methylimidazole) in acetonitrile as the reaction medium. It must be noted
I
however that those Cu species are known to be of limited stability, oligopyridine N-heterocycles
are rather expensive and H O inhibits reactivity in that system. Moreover, studies of new Cu-
2
TEMPO catalytic systems are necessary to shed light on mechanistic aspects of these processes
[
23-28], serendipitous discoveries still having place. [22, 29, 30] This still motivates the scientists
to look for new catalytic systems and the inspiration could also come from the nature itself. [31-
3] Copper biochemistry was given significant attention due to important role it plays in active
sites of metalloenzymes, allowing among others for oxygen activation and reduction processes.
34, 35] One may distinguish two general classes of enzymes, where the copper active sites are
3
[
either co-operating (e.g. catechol oxidase or tyrozinase) or the single metallic centre performs
selective biological transformations (e.g. amine oxidase or galactose oxidaze), with imidazole
moieties (mostly) playing the part of the N-heterocyclic scaffold. [36] Furthermore, the aspect of
cooperativity (or its lack) in the copper-mediated catalytic transformations was emphasized. [27]
In view of the above aspects, we surmised that by applying the tridentate N-heterocyclic Schiff
II
base scaffold and using stable Cu ion as the metallic centre, we would be able to provide
selective catalytic systems for the TEMPO-mediated oxidation reactions. Up to our knowledge,
benzothiazole-based copper(II) systems were not yet evaluated for such processes. At the same
time, different choice of the counterions allowed us to tune the activity of synthesized species,
herein showing the enhanced activity of the bimetallic assemblies in comparison to the
monometallic ones. Our aim of environmental reaction conditions - water as the reaction medium
and air as oxidant - followed by tridentate character of the synthesized ligand all resulted in
slightly sacrificed activity of catalytic species. On the other hand, thanks to this reactivity-
limitation, we were able to show that the benzothiazole-decorated hydrazone Schiff base ligand is
II
potent scaffold for generation of selective Cu catalysts that follow the green chemistry notions.
2
. Experimental section

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2
.1. Materials and methods
-Chlorobenzothiazole, methylhydrazine, 2-benzoylpyridine and metal salts were used as
2
supplied Aldrich without any further purification. Intermediate product A was synthesized as
-4
reported by us previously.[37] ESI mass spectra for acetonitrile solutions ~10 M were measured
using a Waters Micromass ZQ spectrometer. All NMR Spectra were recorded on Bruker Fourier
3
00 MHz spectrometer. NMR solvents were purchased from Aldrich, and used as received.
1
13
Spectra were referenced at solvent residual peaks ( H: (CD ) CO: 2.05 ppm, C: 29.84 ppm,
3
2
1
96.8). IR spectra were obtained with a Perkin–Elmer 580 spectrophotometer and peak positions
-1
are reported in cm . Chromatographic measurements were carried out on a Brucer Scion 436-GC
series gas chromatograph (helium as carrier gas) with a 30 m Varian DB-5 0.25 mm capillary
column and a Scion SQ-MS mass spectrometry detector, whereas the analyses of the
chromatographic peaks were done by the corresponding Brucer MS Workstation 8 software. The
temperature program was as follows: 60°C (3 min), 10°C/min, 250°C (15 min). Quantum
mechanical calculations for systems in the possible reaction pathways were performed with
Gaussian 09 [38] software package at the DFT(B3PW91)/6-31G* level. [39-44] The molecular
geometries were fully optimized at 298 K in vacuo and with the PCM-model to account for the
effect of solvent. The details are in the SI.
2
.2. Catalytic activity studies
Oxidation reactions of alcohols under atmospheric pressure of air were carried out in 10 mL
round-bottom flask equipped with a condenser. The reaction mixtures were prepared as follows:
0
.01 mmol (1 mol% based on substrate) of the Cu catalyst, 0.05 mmol (5 mol%) of TEMPO, 1
mmol of substrate and 3.33 mL of 1M K CO aqueous solution. The reaction solutions were
2
3
stirred for 24 h at 40 °C. After the oxidations 1 M HCl for neutralization and 5 mL of diethyl
ether for the extraction were added. The organic phase was analyzed by GCMS chromatography.
The quantitative analysis was carried out using GCMS chromatography.
2
.3. Synthesis of 2-(1-methyl-2-(phenyl(pyridin-2-yl)methylene)hydrazinyl)benzothiazole
(L)
2
-Benzoylpyridine (1.04 g, 5.67 mmol) was added to
a
solution of 2-(1-
methylhydrazinyl)benzothiazole (1.02 g, 5.67 mmol) in ethanol. The mixture was stirred and
o
heated at 60 C for 48 hours. The product was isolated by evaporation of the solvent and
recrystallization of the residue from a minimum volume of CH CN by the gradual addition of
3
diethyl ether/hexane mixture, filtration and vacuum drying. Yield: 79 % (1.54 g). ESI-MS: m/z
+
(
%) = 345 [L+H] (100).
1
H NMR (300 MHz, Acetone-d6) δ 8.04 (ddd, J = 4.8, 1.8, 1.0 Hz, 1H), 7.70 (dt, J = 8.1, 1.1 Hz,
1
1
H), 7.50 (ddd, J = 8.1, 7.5, 1.8 Hz, 1H), 7.42 (ddd, J = 7.9, 1.3, 0.6 Hz, 1H), 7.15 (ddd, J = 8.1,
.2, 0.6 Hz, 1H), 7.05 – 6.85 (m, 7H), 6.73 (ddd, J = 7.9, 7.3, 1.2 Hz, 1H), 2.67 (s, 3H).

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1
3
C NMR (75 MHz, (CD ) CO): δ ppm 161.3, 146.3. 142.1, 141.3, 139.0, 127.1, 125.4, 122.5,
3
2
1
20.0, 119.3, 118.3, 116.2, 114.2, 112.7, 111.9, 111.7, 110.3, 21.0. IR (KBr): ν(C-H) 3049;
ar
ν (CH ) 2942; ν (CH ) 2863; ν(C=N) 1523; ν(C=C) 1594, 1578, 1561, ν(C-N) 1465, 1444;
as
3
s
3
imin
ar
ν(C=N) 1298, 1281, 1217; ρ(C-H) 1165, 1156, 1142, 1127; γ(C-H) 861, 796, 754, 729, 697,
ar
ar
ar
-1
6
56, 583 cm . Anal calc. For C H N S (344.43): C, 69.74; H, 4.68; N, 16.27; Found: C, 69.85;
20 16 4
H, 4.78; N, 16.14 %
2
2
.4. Synthesis of complexes
.4.1. Synthesis of 2[CuL(NO ) ]·1.25MeCN (1)
3
2
A mixture of Cu(NO ) ·3H O (200 mg, 0.83 mmol) and ligand L (285 mg, 0.83 mmol) in a
3
2
2
mixture of MeOH:CH Cl in 1:1 volume ratio (30 mL) was stirred at room temperature for 24 h.
2
2
The product was isolated by evaporation of solvents and recrystallization of the residue from a
minimum volume of MeOH by the gradual addition of diethyl ether to obtain complex 1 as a
green solid. Crystal appropriate for X-ray diffraction was obtained by vial to vial diffusion of
o
Et O to MeCN/MeOH solution of complex at 4 C. Yield: 77.1 % (357 mg, 0.64 mmol)
2
+
+
+
+
ESI-MS: m/z (%) = 345 [H+L] (100), 367 [Na+L] (35); 407 [Cu(L-H)] (90); 469 (CuL(NO )]
3
(
85). IR (KBr): ν(C-H) 3045; ν (CH ) 2946; ν (CH ) 2864; ν(C=N)
1522; ν(C=C) 1592,
imin ar
ar
as
3
s
3
1
7
3
573, 1565, ν(C-N) 1461, 1442; ν(C=N) 1293, 1283, ρ(C-H) 1161, 1144, 1129; γ(C-H) 865,
ar ar ar
-1
92, 752, 584 cm . Anal calc. for [Cu(C H N S)(NO ) (MeCN)0.625] (557.65): C. 45.77; H.
2
0
16
4
3 2
.23; N, 16.64; Found: C. 45.59; H. 3.30; N, 16.72 %.
2
.4.2. Synthesis of [CuL(µ-SO ) CuL]·2MeOH (2)
4
2
A mixture of CuSO ·5H O (300 mg, 1.20 mmol) and ligand L (414 mg, 1.20 mmol) in a mixture
4
2
of MeOH:CH Cl in 1:1 volume ratio (35 mL) was stirred at room temperature for 24 h. The
2
2
product was isolated by evaporation of solvent and recrystallization of the residue from a
minimum volume of MeOH by the gradual addition of diethyl ether to obtain complex 2 as a
green solid. Crystal appropriate for X-ray diffraction was obtained by vial to vial diffusion of
o
Et O to MeOH solution of complex at 4 C. Yield: 72.1 % (928 mg, 0.87 mmol).
2
+
+
+
ESI-MS: m/z (%) = 345 [H+L] (70), 407 [Cu(L-H)] (10), 442 [CuLCl] (100).; IR (KBr): ν(C-
H) 3027; ν (CH ) 2952; ν (CH ) 2872; ν(C=N) 1532; ν(C=C) 1572, 1552, 1549, ν(C-N)
1
ar
as
3
s
3
imin
ar
-1
473, 1438; ν(C=N) 1283, 1253, ρ(C-H) 1184, 1164, 1121; γ(C-H) 885, 799, 749, 572 cm .
ar ar ar
Anal. calc. for [Cu (C H N S) (SO ) ]·2CH OH (1072.17): C, 47.05; H, 3.75; N, 10.45; Found:
2
20 16
4
2
4 2
3
C, 47.11; H. 3.87; N, 10.40 %.
2
.4.3. Synthesis of [(CuL(µ-F) CuL)(BF ) ]·2MeOH (3)
2
4 2
A mixture of Cu(BF ) (300 mg, 1.26 mmol) and ligand L (436 mg, 1.26 mmol) in a mixture of
4
2
MeOH:CH Cl 1:1 volume ratio (30 mL) was stirred at room temperature for 24 h. The product
2
2
was isolated by evaporation of solvents and recrystallization of the residue from a minimum

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volume of MeOH by the gradual addition of diethyl ether to obtain complex 3 as a green solid.
Crystal appropriate for X-ray diffraction was obtained by vial to vial diffusion of Et O to MeOH
2
o
solution of complex at 4 C. Yield: 76.3 % (988 mg, 0.97 mmol).
+
+
ESI-MS: m/z (%) = 345 [H+L] (30), 442 [CuLCl] (90). IR (KBr): ν(C-H) , 3041; ν(CH ) 2959;
ar
3
ν(CH ) 2877; ν(C=N)
1537; ν(C=C) 1565, 1545, 1529, ν(C-N) 1479, 1431; ν(C=N) 1281,
ar ar
3
imin
-1
1
259, ρ(C-H)ar 1188, 1173, 1137; γ(C-H)ar 865, 783, 738, 563 cm . Anal. calc. for
[
Cu (C H N S) F (BF ) (MeOH) ] (1092.13): C, 46.21; H, 3.69; N, 10.26; Found: C, 46.79; H,
2
20 16
4
2
2
4 2
2
3
.24; N, 10.34 %.
.4.4. Synthesis of [CuLCl ] (4)
2
2
A mixture of CuCl ·2H O (200 mg, 1.17 mmol) and ligand L (404 mg, 1.17 mmol) in a mixture
2
2
of MeOH:CH Cl in 1:1 volume ratio (30 mL) was stirred at room temperature for 24 h. The
2
2
product was isolated by evaporation of solvents and recrystallization of the residue from a
minimum volume of MeOH by the gradual addition of diisopropyl ether to obtain complex 4 as a
green solid. Crystal appropriate for X-ray diffraction was obtained by vial to vial diffusion of
o
iPr O to MeOH solution of complex at 4 C. Yield: 85.2 % (477 mg, 1.00 mmol).
2
+
+
ESI-MS: m/z (%) = 407 [Cu(L-H)] (10), 442 [CuLCl] (90). IR (KBr): ν(C-H) 3041; ν (CH )
ar
as
3
2
1
959; ν (CH ) 2877; ν(C=N)
1537; ν(C=C) 1579, 1537, 1518, ν(C-N) 1488, 1422; ν(C=N)
s
3
imin ar ar
-1
261, 1245, ρ(C-H) 1196, 1184, 1149; γ(C-H) 873, 795, 748, 571 cm . Anal. calc. for
ar
ar
[
Cu(C H N S)Cl ] (478.88): C, 50.16; H, 3.37; N, 11.70; Found: C, 50.08; H, 3.50; N, 11.62 %
20 16 4 2
2
.4.5. Synthesis of [CuL(MeOH)(CF SO )(H O)](CF SO ) (5)
3 3 2 3 3
A mixture of Cu(CF SO ) (200 mg, 0.55 mmol) and ligand L (190 mg, 0.55 mmol) in a mixture
3
3 2
of MeOH:CH Cl in 1:1 volume ratio (30 mL) was stirred at room temperature for 24 h. The
2
2
product was isolated by evaporation of solvents and recrystallization of the residue from a
minimum volume of MeOH by the gradual addition of diethyl ether to obtain complex 5 as a
o
green solid. Crystal appropriate for X-ray diffraction was obtained by vial to vial diffusion at 4 C.
Yield: 80.3 % (335 mg, 0.44 mmol).
+
+
ESI-MS: m/z (%) = 345 [H+L] (100), 407 [Cu(L-H)] (90). IR (KBr): ν(C-H) 3053; ν (CH )
ar
as
3
2
1
972; ν (CH ) 2877; ν(C=N)
1553; ν(C=C) 1581, 1547, 1525, ν(C-N) 1488, 1422; ν(C=N)
s
3
imin ar ar
-1
279, 1235, ρ(C-H) 1187, 1172, 1137; γ(C-H) 891, 782, 723, 551 cm . Anal. calc. for
ar
ar
[
Cu(C H N S)(CF SO )(MeOH)(H O)](CF SO )] (756.17): C, 36.53; H, 2.93; N, 7.41; Found:
20 16 4 3 3 2 3 3
C, 36.40; H, 2.99; N, 7.35 %.
3
. Results and discussion
3
.1. Synthesis of ligand L and complexes 1-5

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The ligand L was synthesized in two-step reaction as shown in Fig. 1.
Fig. 1. Two-step synthesis of benzothiazole ligand L obtained in the study.
2
-(1-Methylhydrazinyl)benzothiazole (A) was obtained from 2-chlorobenzothiazole in
nucleophilic substitution reaction with methylhydrazine in anhydrous ethanol. Further
condensation reaction of synthesized intermediate with benzoylpyridine gave ligand L in 79 %
overall yield. The new coordinating agent was characterized by spectroscopic and analytical
methods, which confirm the purity of the sample (Figs. S1 and S2). It was designed so as to
ensure one, tridentate binding pocket (with SNN or NNN coordination motif) that should
coordinate d block metal ions and thus form stable, open-species complexes of potential utility in
catalysis.
II
Upon complexation with Cu cation, 5 different coordination compounds 1-5 (Fig. 2) were
obtained that differ in the counterion chosen during the synthesis: nitrate (1), sulfate (2),
tetrafluoroborate (3), chloride (4) and trifluoromethanesulfonate (5). Our motivation was to
determine the effect of the anion coordination strength as well as its charge on the formation of
(potentially) catalytically active species in the reaction of alcohol oxidation.
All of the reactions of L with copper(II) salts were carried out in 1:1 ratio of ligand:metal ion in
the mixture of methanol and dichloromethane (1:1 volume ratio) at room temperature for 24h.
The complexes were isolated with good to very good yields (60–80%) by precipitation from their
methanolic solutions using diethyl ether. In all cases, formation of complexes in their original
oxidation state was efficient and the products were readily isolated as stable, green solids. Single
crystals of complexes 1 – 5 suitable for X-ray structure determination were obtained by slow
diffusion of diethyl ether into their methanolic or acetonitrile solutions. This allowed for
unambiguous determination of the ligands binding mode as well as architecture (mono- vs
bimetallic) of obtained species, resulting in the following complexes: 2[CuL(NO ) ]·1.25MeCN
3
2
(1), [CuL(µ-SO ) CuL]·2MeOH (2), [CuL(µ-F) CuL](BF ) ·2MeOH (3), [CuLCl ] (4),
4 2 2 4 2 2
[
CuL(MeOH)(CF SO )(H O)](CF SO ) (5). Of particular notice was the observation that free
3
3
2
3
3
fluoride anion was generated from tetrafluoroborate moiety and coordinates to two cationic
centres in the bridging fashion in 3. An examples of such fluoride abstraction from
tetrafluoroborate anions were observed in the literature and could be ascribed to stronger Lewis
acid character of certain transition metal ions than the BF itself, also facilitated by steric effects
3
of the organic ligand.[45-48]ESI-MS studies indicate formation of copper(II) species, with only
monometallic structures observed under ionisation conditions, nonetheless this behaviour is

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amenable to cone voltage and is known to occur. UV-Vis studies show that the form of the
complexes in solution is dependent on the solvent chosen and their spectral profile is time-
dependent. (Figs. S3-S5) The solvent mixture that was used during the synthesis (CH Cl /MeOH)
2
2
follows what was established in the solid state - two sets of spectra are observed, which are
similar for monometallic (1,4,5) and bimetallic (2,3) systems within each group. Studied
copper(II) complexes are also stable in water as a catalytic medium for further organic
transformation and in the presence of K CO , though a time-dependent hipsochromism of bands
2
3
is observed. With base in the system it is even more profound, nonetheless please notice that this
goes in line the results obtained from catalytic studies. Since the optimum concentration of active
species was 1 mol% for monometallic and 0.5 mol% for bimetallic species, lower activity of the
latter one can be related to the gradual decomplexation of copper(II) species.
3
.2. Crystal structures and geometrical analyses of copper(II) complexes
The type of coordination compound (mono- vs bimetallic) formed and the mode of ligands
binding were unambiguously established by single crystal X-ray diffraction for all 5 compounds
and are shown in Fig. 2.
Fig. 2. Thermal-ellipsoid representations of copper(II) complexes 1-5 (a-e) synthesized in the present study. Details
of specific contacts and symmetry elements are provided in the supplementary information (Figs. S6-S10).
II
Schiff base ligand L acts as tridentate one and coordinates Cu ions by three nitrogen atoms (N3,
N12 and N21). Interestingly, in all cases aromatic parts of the ligand molecule (condensed ring
system, linker and pyridine ring) are almost planar, the dihedral angles between the terminal ring
planes are between 1.9° and 11.4°. One could envisage that the methyl and pyridine moieties
should interact and thus result in deformations of the above-noted dihedral angle, nonetheless it is

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not the case herein. Such conformation allows all three coordination centers to be in the similar
distance from the central ion. The spread of the Cu-N distances is very narrow: 1.956Å – 2.032Å.
There are examples of mono- (1, 4, 5) and bimetallic (2, 3) complexes. The latter ones are Ci-
symmetrical; the copper ions are bridged by oxygen atoms from sulphate ions (2) or by fluorine
II
ions (3). The Cu ions are in most of the cases 5-coordinated, and the coordination geometry is
close to tetragonal pyramid. The tau parameters are close to ideal value of 0 (0.03° – 0.27°) and
are listed in Table S2, together with SHAPE [49] analysis.
True octahedral coordination is found only in 3, there are also doubtful cases of 1 and 5, when the
sixth contact is significantly longer than the others (longer than 2.5 Å), and therefore the very
existence of such interaction is far from obvious. The latter has been also supported by SHAPE
analysis, which was conducted for the sake of symmetry comparisons as well as to gain deeper
knowledge about structure/properties relations with regard to the alcohol oxidation. Tables S2
and S3 gather calculations from the point of view of continuous shape measurements (SChM) for
CN = 5 (1, 2, 4, 5) and CN = 6. (1, 3, 5).
Compound 1 was subjected to calculations that include cases of both with and without
II
II
consideration of the O NO-Cu distances that are above 2.6Å and they clearly show that Cu
2
coordination spheres therein are more appropriately described as 5-coordinated spheres of C4v
symmetry instead of the octahedral ones. It is of note that the lowest values in Table S3
correspond to O symmetry (1- Cu1A: 5.840, 1- Cu1B: 6.495 and 5 – Cu1: 6.945) nonetheless it
h
has been established that CShM values that are above 3 indicate important distortions[49], what
II
is in line with above considerations. In case of complex 5 that exhibits OTf-Cu bonding,
II
omission of the longest anion-Cu contact was also calculated, albeit obtained CShM values are
acceptable for both coordination numbers. From the CN = 5 series, all but one complex (2) are
better described as classical (Berry) square pyramid, whereas the sulphate dimer is more similar
in nature to octahedron yet with one vacant vertex (Johnson square pyramid, J1).[50]
Interestingly, similar CShM values for Cu1A in 1 (1.276; 1.340) led us to question whether or not
it belongs to the interconversion path between Berry and Johnsons square pyramids, yet
calculated deviation threshold (73.2 %) is too large for Cu1A to belong therein. From the CN = 6
series, octahedral geometry is the only reference shape that gives reasonable CShM values for
compounds 3 and 5 although certain deviations from perfect symmetry are observed, accounted
II
to the Jahn-Teller effect observed for Cu species.
In the crystal structures the solvent molecules can be often found to fill the voids between the
complex molecules; an example of such crystal packing (1) is shown in Fig. S11. In the complex
5
, in which there are classical hydrogen bond donors, these interaction play also an important role
in the determination of its crystal architecture.
3
.3. Catalytic activity of copper(II) complexes

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Recent studies on similar systems showed that bimetallic individuals might be responsible for
I/II
more efficient catalysis with regard to Cu mediated oxidation reactions[51] [ 52] therefore
,
compound 3 from 1-5 was chosen as the starting point for evaluation of their catalytic activity.
Initial screening tests showed that TEMPO/air/3 system leads to 27% conversion of benzylic
alcohol to benzaldehyde after 5h under ambient conditions (Table 1 – entry 1).
Table 1 Optimization of the reaction conditions for aerobic oxidation of benzyl alcohol to the corresponding
aldehydes
b
a
c
Entry
Catalyst
Conversion [%]
Variations
5h, RT
Selectivity
100
100
100
83.3
84.8
-
1
2
3
4
5
6
7
8
9
3
3
3
3
3
3
2
2
2
3
3
3
2
2
2
27
64
100
78
79
1
77
90
89
100
56
42
90
70
35
50
33
RT
-
2,5 mol% TEMPO
0,5 M K CO3
no TEMPO
-
2
100
100
100
100
100
100
100
100
100
100
100
o
50 C
o
Catalyst formed in situ from L and CuSO , 50 C
4
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
1.25 mol% of 3
0.5 mol% of 3
0.25 mol% of 3 o
1.25 mol% of 2, 50 C
o
0.5 mol% of 2, 50 C
0.25 mol% of 2, 50 C
o
CuSO4
Cu(BF4)2
-
-
a
Standard conditions (unless noted otherwise in the table) 0.01 mmol (1 mol% based on substrate) of the Cu catalyst,
0
4
.05 mmol (5 mol%) of TEMPO, 1 mmol of substrate and K CO aqueous solution (3.33 ml, 1 M), 1 atm, air, 24h,
2
3
o
b
0 C; measured by GC-MS, overall yield of carbonyl products i.e. moles of products (aromatic aldehyde and
c
acid)/100 moles of alcohol; molar amount of benzaldehyde/total amount of products x 100
Prolonging the reaction time leads to improvement of conversion (64 % - entry 2), whereas
quantitative (100% - entry 3) and selective (overoxidation to benzoic acid was not observed)
o
oxidation was found upon 24 h of stirring under 40 C. It must be noted that lowering the amount
of TEMPO (from 5 mol% to 2.5 mol% - entry 4) or K CO (from 1 M to 0.5 M – entry 5) leads to
2
3
losses in conversion and selectivity, whereas the former one is indispensable for the oxidation to
occur (no TEMPO - entry 6). Such observations also confirm the role of TEMPO as an effective
radical trap. [5] In addition, initial screening was also performed on compound 2 (bimetallic
o
sulphate analogue – entries 7-9, 13-15), nonetheless even at higher temperature (50 C – entry 8)
maximum of 90% conversion was achieved, which is still lower than for 3, though higher than
for monometallic (1, 5) species (Table 2, entries 2 and 5). It was shown by Ahmad et al. that
copper catalyzed oxidations in the presence of sulfates usually necessitate high temperatures. [53]

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Identical reaction performed in the presence of 2 formed in situ from CuSO and ligand L lead to
4
similar activity (entry 9).
Optimal Cu catalyst concentration was found to be 1 mol% based on the substrate, since lowering
of concentration led to the reduced conversion of alcohol (entries 11, 12 – compound 3; 14, 15 –
compound 2; Fig. S12). Importantly, selectivity in such systems was still preserved, which is
important in case that gradual deactivation of the active species was to occur.
Please note that actual concentration of copper catalyst would be 0.5 mol% if calculated per one
metallic center. Interestingly, the highest conversion of alcohol with 2 as catalyst was observed
o
when the temperature was 50 C (entries 13 and 14), what could indicate that redox changes
associated with reaction mechanism are hindered when dianionic counterion is used. Control
experiments also showed that CuSO and Cu(BF ) alone (copper salts used for syntheses of 2
4
4 2
and 3) lead to the significant loss in activity (entries 16 and 17) which proves that new Schiff
base ligand scaffold favors the observed high catalytic activity.
Therefore, with optimal conditions to perform selective oxidation of benzyl alcohol in hand, the
effect of varying the counterion on the effectiveness of the process was studied (Table 2).
a
Table 2 Aerobic oxidation of selected benzylic alcohols to the corresponding aldehydes
b
c
Entry
Catalyst
Substrate
benzyl alcohol
benzyl alcohol
benzyl alcohol
benzyl alcohol
benzyl alcohol
Product
benzaldehyde
benzaldehyde
benzaldehyde
benzaldehyde
Conversion [%]
Selectivity
100
1
2
3
4
5
7
8
9
3
1
2
4
5
1
1
2
2
2
2
3
3
3
3
100
63
100
100
100
100
100
100
100
100
100
100
100
100
100
85.9
d
90
92
75
64
60
benzaldehyde
4-Me-benzyl alcohol
4-Br-benzyl alcohol
4-Me-benzyl alcohol
4-Br-benzyl alcohol
4-OMe-benzyl alcohol
4-F-benzyl alcohol
4-Me-benzyl alcohol
4-Br-benzyl alcohol
4-OMe-benzyl alcohol
4-F-benzyl alcohol
4-Me-benzaldehyde
4-Br-benzaldehyde
4-Me-benzaldehyde
4-Br-benzaldehyde
4-OMe-benzaldehyde
4-F- benzaldehyde
4-Me-benzaldehyde
4-Br-benzaldehyde
4-OMe- benzaldehyde
4-F- benzaldehyde
bicyclo[2.2.1]heptan-2-
one
d
90
83
98
80
d
1
1
1
1
1
1
1
0
1
2
3
4
5
6
d
d
80
87
98
99
1
1
1
2
7
8
9
0
3
3
3
3
exo-norborneol
0
0
0
0
-
-
-
-
1-cyclopropylethanol
cis-2-
methylcyclohexanol
3-buten-2-ol
1-cyclopropylethanone
(S)-2-
methylcyclohexanone
but-3-en-2-one
a
Optimized conditions: 0.01 mmol (1 mol% based on substrate) of the Cu catalyst, 0.05 mmol (5 mol%) of TEMPO,
o
b
1
mmol of substrate and K CO aqueous solution (3.33 ml, 1 M), 40 C, 1 atm, air; 24h measured by GC-MS,
2 3
c
overall yield of carbonyl products i.e. moles of products (aromatic aldehyde and acid)/100 moles of alcohol; molar
d
o
amount of benzaldehyde/total amount of products x 100; reaction performed at 50 C

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Copper(II) compounds with benzothiazole scaffolded ligand L (1-5) displayed fair to excellent
conversions (entries 1-5; 63-100%), with monometallic chloride 4 and bimetallic sulphate 2 as
well as mixed fluoride/tetrafluoroborate 3 being the most efficient. This would fall in line with
results obtained by Zhang et al. [51] for similar N complexes of 2,2’:6’,2’’- terpyridine (tpy)
3
ligands, since such N -meridional framework followed by bridging species would facilitate
3
I
II
formation of active mixed valence Cu Cu assemblies. Despite that 4 is monometallic in the solid
state, chloride architectures of this kind are known to form -chlorido species with TEMPO [54],
thus excellent yields are observed for this compound as well.
Investigated protocol was expanded to other alcohols so as to gain insight into the scope and
limitations as far as applicability of the studied copper(II) complexes is concerned. Results of
catalytic studies obtained for monometallic 1 (entries 7, 8) showed that p-substituted benzyl
alcohols were also oxidized, albeit with fair yields, possibly due to strong coordinating character
of the nitrate anions. Higher conversion is achieved when bridged dinuclear compounds 2 and 3
are used (entries 9-16), which is applicable for both electron withdrawing (F, Br) and electron
donating groups (Me, OMe), with the latter ones being activating moieties, thus facilitating
conversion. Interestingly, when fluorine was present as the moiety both in benzylic alcohol and
II
as the bridging entity between Cu centers, overoxidation to acid was observed (ca. 6:1 of
aldehyde:acid). Despite slight loss of selectivity therein, it is important aspect that is planned on
to pursue further, i.e. that mimicking the target substrate with the structure of the catalyst may
synergically lead to higher catalytic activity than when treated individually. Such behavior is yet
unprecedented for such group of compounds, bearing in mind that similar N -meridional -
3
bridged fluoro-copper(II) complexes are very scarce. Attempts to oxidize cyclic (entries 17-19)
and allyl (entry 20) secondary alcohols with the most active catalyst 3 proved to be unsuccessful,
nonetheless such a situation in copper mediated TEMPO systems is not unprecedented. [51, 55]
This may however be perceived as a virtue for selective oxidation of molecules scaffolded with
various hydroxyl groups, where some of them must stay intact.
3
.4. Proposed reaction mechanism
It has been clearly established that the catalytic cycle of alcohol oxidation is associated with one
I
II
electron Cu /Cu redox changes [1] and with TEMPO being indispensable for the process to
I
occur (Table 1 – entry 6). That Cu metallic center is necessary is supported by enhanced activity
of dinuclear complexes 2-4 (Table 2 – Entries 1, 2, 4) as well as aforementioned mixed valence
I
II
(
tpy)Cu Cu assemblies[51], which would stabilize entities with bridged -halide (3, 4) or -
sulphate groups (2). In addition, it was found that the presence of base is mandatory for the
reaction to occur.
Although detailed mechanism of Cu/TEMPO oxidation is still debatable, thanks to mechanistic
studies on similar systems[24-26],[56,57] , results observed in this paper as well as DFT studies
performed herein (Figs S13, S14, Tables S4, S5), we propose the following, most plausible
reaction mechanism to take place, as shown on compound 3 (Fig. 3).

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Fig. 3. Schematic representation of mechanistic pathway towards oxidation of benxylic acohols to their
corresponding aldehydes for monometallic compounds, as exemplified on 3. Capital letters denote species that were
optimized by DFT methods.
For the sake of clarity and due to computational demand of DFT calculations, the monometallic
catalytic pathway is presented, though the one involving the bimetallic 3 [CuL(µ-F) CuL](BF4)2
2
can also be constructed and will be referred to as well.
II
Starting from Cu -complex, three main stages of the reaction may be distinguished: (i) formation
II
of the [Cu -alkoxide] complex (3AB) and oxidation of the alcohol (BC); (ii) oxygen
activation (CD) and formation of peroxo-species (DE); (iii) activation of the alcohol to
regenerate the alkoxy complex (EA/B). [25]
Of relevance for stage (i), one may envisage that mono- and dinuclear structures that are formed
in the solid state may interexchange and thus result in a mixture of those in solution, possibly
with hydroxyl ligated species (3A) - Fig. S15. Consequently, coordination of alcohol or its
II
deprotonated form results in equilibrated formation of [Cu -alkoxide] complexes (AB) - Fig.
S16, which are of reminiscence to the galactose oxidase system.[58, 59] Next step involves
oxidation of the above formed intermediate (BC) with TEMPO, and is one of the most debated
II
stages of the reaction. Three [TEMPO-Cu -F-L-ArO] transition states of organic radical with
II
copper-alkoxide were thoroughly studied in literature on the seminal [bpy-Cu -NMI] system and
differ in the role of TEMPO on the oxidation step.[17, 23, 25, 26, 56] On that basis, we
anticipated the possible interaction modes of organic radical in our system (Fig. S17) and since
DFT calculations excluded the possible binding of TEMPO to copper ion in our system, we

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assume that oxidation proceeds via intermolecular hydrogen-atom transfer (HAT) to generate
TEMPO(OH) and benzaldehyde. Indeed, gas-phase B-C transition state was calculated and is
−
1
shown on Fig. S18 as TS-1. The imaginary vibration (14 i cm ) found for TS-1 corresponds to
the simultaneous (i) C-H stretching of one of two hydrogen atoms of benzyl alcohol ligand in the
direction of TEMPO oxygen atom (the C-H bond is elongated to 1.190Å in the saddle point
structure) (ii) the displacement of the second hydrogen atom in the direction of the aromatic C–
C–O plane (enabling formation of benzaldehyde). We found that the kinetic barrier associated
with this saddle point to be equal 46.9 kcal/mol (Fig. S14). Once the hydrogen transfer is done
and TEMPO(OH) is formed, whole complex should spontaneously (i.e., through a negligibly
small kinetic barrier) dissociate the benzaldehyde forming C. It can be also clearly observed that
this is the rate determining step of the whole process. The alternative scenario with hypothesized
II
TEMPO coordinated to the Cu center is presented on Fig. S19. We observed that it causes
breaking of two other dative bonds which changes structure of the system altogether. We believe
that the main reason for TEMPO not to be coordinated in order for HAT to happen is rather long
distance between hydrogen atom to be transferred from benzyloxide ligand to the oxygen atom of
coordinated TEMPO ligand. Second reason for that is the steric hindrance caused by methyl
substituents in TEMPO ring.
This is an interesting feature, since even though HAT mode was proposed to occur in some other
studies [17, 23, 26, 51], it was later shown[25, 56] that oxidation might proceed through direct
coordination of TEMPO to copper ion through either five- or six-membered transition state.[24,
2
5] We ascribe this difference to the fact of ligands denticity, since tridentate character (contrary
II
to the bidentate mode of bpy) of L precludes TEMPO from coordination to Cu ion. It is in line
with additional studies on copper-alkoxides, since those intermediates are postulated to influence
the C-H bond strength of deprotonated alcohol[60] and under certain conditions may behave as
hydrogen atom acceptors [61], therefore hindering oxidation of non-activated alcohols. This
would explain the herein observed catalytic activity with regard to the oxidation of benzylic
alcohols and lack of such for compounds with secondary hydroxyl groups.
II
Next stage (ii) involves regeneration of Cu catalyst and TEMPO radical, which we propose to
proceed via oxygen activation and formation of peroxo-species (Fig. S20). Coordination of
II
·-
dioxygen (CD) results in formation of oxidized monometallic complex [LCu (F)(O )], which
2
is the global minimum according to our DFT calculations, no matter the phase considered. Step
DE results in proton transfer from TEMPO(OH) to the dioxygen complexes formed in the
previous step and such TEMPO regeneration was also proposed in the literature to occur.[25
According to our computations, the aforementioned process is predicted to require significant
amounts of energy from environment to proceed since the Gibbs free energy of the products is
significantly higher than that of the substrates. The calculated TS-2 (Fig. S18) DE transition
-1
state (with the imaginary vibration of 513 i cm ) corresponds to the protonation of coordinated
O by the TEMPO(OH). Formation of this transition state requires surmounting 32.2 kcal/mol
2

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barrier and is associated with elongation of the O-H bond in TEMPO(OH) by the 0.315Å to
1
.283Å in the direction of the coordinated oxygen molecule. We anticipate that bimetallic species
II
·-
II
[
LCu (O )(-F)(F)Cu L] would be less stabilized and resulting in higher global energy
2
minimum than for monometallic ones, hence activation energy would be lower to proceed
further. All in all, this is in line with experimental observations, since our system necessitates
II
heating. Recently, proton-coupled oxidation of TEMPO(OH) by the chosen Cu salts could also
contribute to the catalyst regeneration under aerobic oxidation conditions. [62]
II
The last step (iii) involves regeneration of the [Cu -alkoxide] complex that was the starting point
of the catalytic cycle, which can proceed in two ways (Fig. S21). One is intramolecular proton
transfer to peroxo complex E from coordinated alcohol, which leads to regenerated B and
hydrogen peroxide, as was calculated and proposed by Iron et al.[25] The second one differs in
that the proton comes from water, which also leads to formation of H O and regeneration of
2
2
active complex in the form of A. Given significant excess of water in relation to alcohol, we
propose the latter to be more viable, even though EA/B transitions are computed to be
thermodynamically unfavorable, and EB being slightly energetically less demanding (Fig.
S22). This would mean that it is the step, where bimetallic mode of complex would push the
reaction further, probably due to additional H-bonding present in bis-B.
Finally, tentative proposition of mechanism for bimetallic species is presented in a comparable
way (Fig. S23), which we propose to be similar to the monometallic one, with eventual energetic
hardships being circumvented by additional H-bonding stabilization in bis-B and lower overall
II
stability of bis-D. Upon initial formation of the alkoxy-Cu intermediate, oxidation via HAT
II
mechanism is proposed, followed by regeneration of TEMPO and active Cu complex via the
peroxo route.
4
. Conclusions
II
New hydrazone Schiff base ligand and its five Cu coordination compounds were synthesized,
which form mono- or bimetallic species depending on the chosen counterion. These systems
allow for an efficient and selective oxidation of alcohols that are activated by the presence of
aromatic substituents. On the basis on experimental results, literature studies and DFT
calculations two independent reaction mechanisms were proposed that explain the observed
catalytic efficiency, including enhanced activity of the bimetallic species. Inertness towards
secondary alcohols may be herein considered as virtue, since such behavior would allow one for
selective oxidation of complex molecules that possess multiple oxidizable hydroxyl groups that
differ in reactivity.[24] A sacrifice in activity in favour of selectivity seems to be related to the
tridentate character of the synthesized ligand. Environmentally benign solvent, presence of air as
well as low catalyst loading shall motivate us to study other Schiff base scaffolds[63] so as to
gain better insight into the reasons that render efficient oxidation of alcohols possible.
5
. Acknowledgements

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This work was supported by the Polish National Science Center (grant PRELUDIUM – no.
2
015/17/N/ST5/01973). DFT calculations were conducted by using resources of (a) cluster
Piasek at the Faculty of Chemistry, University of Gdańsk, and (b) the Academic Computer
Center (CI TASK) in Gdańsk.
6
. References
[
1] S.D. McCann, S.S. Stahl, Copper-Catalyzed Aerobic Oxidations of Organic Molecules: Pathways for
Two-Electron Oxidation with a Four-Electron Oxidant and a One-Electron Redox-Active Catalyst, Acc.
Chem. Res., 48 (2015) 1756-1766.
[
2] S.E. Allen, R.R. Walvoord, R. Padilla-Salinas, M.C. Kozlowski, Aerobic Copper-Catalyzed Organic
Reactions, Chemical Reviews, 113 (2013) 6234-6458.
3] Liquid Phase Aerobic Oxidation Catalysis: Industrial Applications and Academic Perspectives:
[
Industrial Applications and Academic Perspectives, Wiley-VCH Verlag GmbH & Co. KGaA: , Weinheim,
Germany, 2016.
[
4] T. Punniyamurthy, S. Velusamy, J. Iqbal, Recent Advances in Transition Metal Catalyzed Oxidation of
Organic Substrates with Molecular Oxygen, Chem. Rev., 105 (2005) 2329-2364.
5] R.A. Sheldon, I.W.C.E. Arends, Organocatalytic Oxidations Mediated by Nitroxyl Radicals, Adv. Synth.
Catal., 346 (2004) 1051-1071.
6] R.A. Sheldon, Metal-catalyzed Oxidations of Organic Compounds: Mechanistic Principles and
Synthetic Methodology Including Biochemical Processes, Academic Press, 2012.
[
[
[
[
7] G. Centi, S. Perathoner, Catalysis and sustainable (green) chemistry, Catal. Today, 77 (2003) 287-297.
8] Z. Shi, C. Zhang, C. Tang, N. Jiao, Recent advances in transition-metal catalyzed reactions using
molecular oxygen as the oxidant, Chem. Soc. Rev., 41 (2012) 3381-3430.
[
9] J. E. Nutting, M. Rafiee, S.S. Stahl, Tetramethylpiperidine N-Oxyl (TEMPO), Phthalimide N-Oxyl (PINO),
and Related N-Oxyl Species: Electrochemical Properties and Their Use in Electrocatalytic Reactions,
Chem. Rev. 118, (2018), 4834-4885.
[
10] H. A. Beejapur, Q. Zhang, K. Hu, L. Zhu, J. Wang, Z. Ye, TEMPO in Chemical Transformations: From
Homogeneous to Heterogeneous, ACS Catal., 9 (2019) 2777-2830.
11] I.E. MarkÓ, P.R. Giles, M. Tsukazaki, I. ChellÉ-Regnaut, A. Gautier, R. Dumeunier, F. Philippart, K.
[
Doda, J.-L. Mutonkole, S.M. Brown, C.J. Urch, EFFICIENT, ECOLOGICALLY BENIGN, AEROBIC OXIDATION
OF ALCOHOLS, in: Advances in Inorganic Chemistry, Academic Press, 2004, pp. 211-240.
[
12] M.N. Kopylovich, A.P.C. Ribeiro, E.C.B.A. Alegria, N.M.R. Martins, L.M.D.R.S. Martins, A.J.L.
Pombeiro, Chapter Three - Catalytic Oxidation of Alcohols: Recent Advances, in: P.J. Pérez (Ed.) Advances
in Organometallic Chemistry, Academic Press, 2015, pp. 91-174.
[
13] O. Das, T.K. Paine, CHAPTER 2 Copper Catalysts for Aerobic Oxidation of Alcohols, in: Transition
Metal Catalysis in Aerobic Alcohol Oxidation, The Royal Society of Chemistry, 2015, pp. 40-69.
14] M.F. Semmelhack, C.S. Chou, D.A. Cortes, Nitroxyl-mediated electrooxidation of alcohols to
aldehydes and ketones, J. Am. Chem. Soc., 105 (1983) 4492-4494.
15] M.F. Semmelhack, C.R. Schmid, D.A. Cortes, C.S. Chou, Oxidation of alcohols to aldehydes with
oxygen and cupric ion, mediated by nitrosonium ion, J. Am. Chem. Soc., 106 (1984) 3374-3376.
16] G. Patrick, A.I.W.C. E., S.R. A., R. Jan, Room Temperature Aerobic Copper–Catalysed Selective
Oxidation of Primary Alcohols to Aldehydes, Adv. Synth. Catal., 346 (2004) 805-811.
17] E.T.T. Kumpulainen, A.M.P. Koskinen, Catalytic Activity Dependency on Catalyst Components in
Aerobic Copper–TEMPO Oxidation, Chem. Eur. J., 15 (2009) 10901-10911.
18] J.M. Hoover, S.S. Stahl, Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective
Aerobic Oxidation of Primary Alcohols, J. Am. Chem. Soc., 133 (2011) 16901-16910.
[
[
[
[
[

Journal Pre-proof
[
19] J.M. Hoover, J.E. Steves, S.S. Stahl, Copper(I)/TEMPO-catalyzed aerobic oxidation of primary alcohols
to aldehydes with ambient air, Nat. Protoc., 7 (2012) 1161.
20] J.E. Steves, Y. Preger, J.R. Martinelli, C.J. Welch, T.W. Root, J.M. Hawkins, S.S. Stahl, Process
Development of CuI/ABNO/NMI-Catalyzed Aerobic Alcohol Oxidation, Org. Process Res. Dev., 19 (2015)
548-1553.
21] J.E. Steves, S.S. Stahl, Copper(I)/ABNO-Catalyzed Aerobic Alcohol Oxidation: Alleviating Steric and
Electronic Constraints of Cu/TEMPO Catalyst Systems, J. Am. Chem. Soc., 135 (2013) 15742-15745.
22] X. Boran, L. Jean-Philip, A.B. A., A TEMPO-Free Copper-Catalyzed Aerobic Oxidation of Alcohols,
Angew. Chem. Int. Ed., 54 (2015) 4208-4211.
23] J.M. Hoover, B.L. Ryland, S.S. Stahl, Copper/TEMPO-Catalyzed Aerobic Alcohol Oxidation:
Mechanistic Assessment of Different Catalyst Systems, ACS Catal., 3 (2013) 2599-2605.
24] B.L. Ryland, S.D. McCann, T.C. Brunold, S.S. Stahl, Mechanism of Alcohol Oxidation Mediated by
Copper(II) and Nitroxyl Radicals, J. Am. Chem. Soc., 136 (2014) 12166-12173.
25] M.A. Iron, A.M. Szpilman, Mechanism of the Copper/TEMPO-Catalyzed Aerobic Oxidation of
Alcohols, Chemistry – A European Journal, 23 (2017) 1368-1378.
26] J.M. Hoover, B.L. Ryland, S.S. Stahl, Mechanism of Copper(I)/TEMPO-Catalyzed Aerobic Alcohol
Oxidation, J. Am. Chem. Soc., 135 (2013) 2357-2367.
27] S.D. McCann, S.S. Stahl, Mechanism of Copper/Azodicarboxylate-Catalyzed Aerobic Alcohol
Oxidation: Evidence for Uncooperative Catalysis, J. Am. Chem. Soc., 138 (2016) 199-206.
28] Z. Liu, Z. Shen, N. Zhang, W. Zhong, X. Liu, Aerobic Oxidation of Alcohols Catalysed by
Cu(I)/NMI/TEMPO System and Its Mechanistic Insights, Catalysis Letters, 148 (2018) 2709-2718
29] M.O. Konev, E.R. Jarvo, Nitroxyl Surprise: A Simple Amine Additive Revealed as Copper’s Co-Catalyst
in the Aerobic Oxidation of Alcohols, ACS Cent. Sci., 3 (2017) 272-274.
30] S.D. McCann, J.-P. Lumb, B.A. Arndtsen, S.S. Stahl, Second-Order Biomimicry: In Situ Oxidative Self-
[
1
[
[
[
[
[
[
[
[
[
[
Processing Converts Copper(I)/Diamine Precursor into a Highly Active Aerobic Oxidation Catalyst, ACS
Cent. Sci., 3 (2017) 314-321.
[
[
[
31] L. Que Jr, W.B. Tolman, Biologically inspired oxidation catalysis, Nature, 455 (2008) 333.
32] M. Largeron, M.-B. Fleury, Bioinspired Oxidation Catalysts, Science, 339 (2013) 43.
33] L. Marais, A. J. Swarts, Biomimetic Cu/Nitroxyl Catalyst Systems for Selective Alcohol
Oxidation, Catalysts, 9 (2019) 395.
34] M. Fontecave, J.-L. Pierre, Oxidations by copper metalloenzymes and some biomimetic approaches,
Coord. Chem. Rev., 170 (1998) 125-140.
35] E.I. Solomon, D.E. Heppner, E.M. Johnston, J.W. Ginsbach, J. Cirera, M. Qayyum, M.T. Kieber-
Emmons, C.H. Kjaergaard, R.G. Hadt, L. Tian, Copper Active Sites in Biology, Chem. Rev., 114 (2014) 3659-
853.
36] A. Messerschmidt, 8.14 - Copper Metalloenzymes, in: H.-W. Liu, L. Mander (Eds.) Comprehensive
Natural Products II, Elsevier, Oxford, 2010, pp. 489-545.
37] M.A. Fik, M. Kubicki, A.E. Odachowska, J. Karpińska, V. Patroniak, Helicity in Photocatalysis –
[
[
3
[
[
Advantage or Obstacle? Studies on Silver Complexes – Synthesis, Structure, and Photocatalytic Activity,
Eur. J. Inorg. Chem., (2016) 5530-5538.
[
38] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V.
Barone, G.A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A.V. Marenich, J. Bloino, B.G. Janesko, R.
Gomperts, B. Mennucci, H.P. Hratchian, J.V. Ortiz, A.F. Izmaylov, J.L. Sonnenberg, Williams, F. Ding, F.
Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V.G. Zakrzewski, J. Gao, N.
Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima,
Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M.J.
Bearpark, J.J. Heyd, E.N. Brothers, K.N. Kudin, V.N. Staroverov, T.A. Keith, R. Kobayashi, J. Normand, K.
Raghavachari, A.P. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, J.M. Millam, M. Klene, C. Adamo,

Journal Pre-proof
R. Cammi, J.W. Ochterski, R.L. Martin, K. Morokuma, O. Farkas, J.B. Foresman, D.J. Fox, Gaussian 09 Rev.
D.01, in, Wallingford, CT, 2009.
[
1
[
39] R. G. Parr, W. Yang, Density Functional Theory of Atoms and Molecular Orbital Theory, New York,
998.
40] A.D. Becke, Density-functional exchange-energy approximation with correct asymptotic behavior,
Phys. Rev. A, 38 (1988) 3098-3100.
41] J.P. Perdew, in: P.Z.a.H. Eschrig (Ed.) Electronic Structure of Solids ‘91, Akademie Verlag, Berlin,
991, pp. 11.
42] J.P. Perdew, J.A. Chevary, S.H. Vosko, K.A. Jackson, M.R. Pederson, D.J. Singh, C. Fiolhais, Atoms,
[
1
[
molecules, solids, and surfaces: Applications of the generalized gradient approximation for exchange and
correlation, Phys. Rev. B, 46 (1992) 6671-6687.
[
43] J.P. Perdew, J.A. Chevary, S.H. Vosko, K.A. Jackson, M.R. Pederson, D.J. Singh, C. Fiolhais, Erratum:
Atoms, molecules, solids, and surfaces: Applications of the generalized gradient approximation for
exchange and correlation, Phys. Rev. B, 48 (1993) 4978-4978.
[
44] J.P. Perdew, K. Burke, Y. Wang, Generalized gradient approximation for the exchange-correlation
hole of a many-electron system, Phys. Rev. B, 54 (1996) 16533-16539.
45] Y. I. Cho, M. L. Ward, M. J. Rose, Substituent effects of N4 Schiff base ligands on the formation of
fluoride-bridged dicobalt(ii) complexes via B–F abstraction: structures and magnetism, Dalton Trans., 45,
[
(
[
2016) 13466-13476
46] A. R. Stefankiewicz, M. Wałęsa-Chorab, J. Harrowfield, M. Kubicki, Z. Hnatejko, M. Korabik, V.
Patroniak, Self-assembly of transition metal ion complexes of a hybrid pyrazine–terpyridine ligand,
Dalton Trans., 42 (2013) 1743-1751.
[
47] D. L. Reger, A. E. Pascui ,M. D. Smith, J. Jezierska, A. Ozarowski, Dinuclear Complexes Containing
Linear M–F–M [M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II)] Bridges: Trends in Structures,
Antiferromagnetic Superexchange Interactions, and Spectroscopic Properties, Inorg. Chem., 51 (2012)
1
1820–11836.
[
48] E. Tomat, L. Cuesta, V. M. Lynch, J. L. Sessler, Binuclear Fluoro-Bridged Zinc and Cadmium Complexes
of a Schiff Base Expanded Porphyrin:ꢀ Fluoride Abstraction from the Tetrafluoroborate Anion, Inorg.
Chem., 46 (2007) 6224-6226.
[
49] S. Alvarez, P. Alemany, D. Casanova, J. Cirera, M. Llunell, D. Avnir, Shape maps and polyhedral
interconversion paths in transition metal chemistry, Coord. Chem. Rev., 249 (2005) 1693-1708.
[
50] N.W. Johnson, Canad. J. Mathematics, 18 (1966) 169-200.
[51] G. Zhang, E. Liu, C. Yang, L. Li, J.A. Golen, A.L. Rheingold, Copper(II) Complexes of 2,2′:6′,2″-
Terpyridine Derivatives for Catalytic Aerobic Alcohol Oxidations – Observation of Mixed-Valence CuICuII
Assembles, Eur. J. Inorg. Chem., 2015 (2015) 939-947.
[
52] G. Zhang, G. Proni, S. Zhao, E.C. Constable, C.E. Housecroft, M. Neuburger, J.A. Zampese, Chiral
tetranuclear and dinuclear copper(ii) complexes for TEMPO-mediated aerobic oxidation of alcohols: are
four metal centres better than two?, Dalton Trans., 43 (2014) 12313-12320.
[
53] J.U. Ahmad, M.T. Räisänen, M. Leskelä, T. Repo, Copper catalyzed oxidation of benzylic alcohols in
water with H2O2, Appl. Catal. A, 411-412 (2012) 180-187.
54] J. Laugier, J.M. Latour, A. Caneschi, P. Rey, Structural and redox properties of the Tempo adducts of
copper(II) halides, Inorg. Chem., 30 (1991) 4474-4477.
55] Z. Ma, L. Wei, E.C.B.A. Alegria, L.M.D.R.S. Martins, M.F.C. Guedes da Silva, A.J.L. Pombeiro, Synthesis
[
[
and characterization of copper(ii) 4[prime or minute]-phenyl-terpyridine compounds and catalytic
application for aerobic oxidation of benzylic alcohols, Dalton Trans., 43 (2014) 4048-4058.
[56] J. Rabeah, U. Bentrup, R. Stößer, A. Brückner, Selective Alcohol Oxidation by a Copper TEMPO
Catalyst: Mechanistic Insights by Simultaneously Coupled Operando EPR/UV-Vis/ATR-IR Spectroscopy,
Angew. Chem. Int. Ed., 54 (2015) 11791-11794.

Journal Pre-proof
[
57] S. Adomeit, J. Rabeah, A.E. Surkus, U. Bentrup, A. Brückner, Effects of Imidazole-Type Ligands in
CuI/TEMPO-Mediated Aerobic Alcohol Oxidation, Inorg. Chem., 56 (2017) 684-691.
58] G. Avigad, D. Amaral, C. Asensio, B.L. Horecker, The d-Galactose Oxidase of Polyporus circinatus, J.
Biol. Chem., 237 (1962) 2736-2743.
59] M.M. Whittaker, J.W. Whittaker, The active site of galactose oxidase, J. Biol. Chem., 263 (1988)
074-6080.
60] E.C. Hayes, T.R. Porter, C.J. Barrows, W. Kaminsky, J.M. Mayer, S. Stoll, Electronic Structure of a CuII–
Alkoxide Complex Modeling Intermediates in Copper-Catalyzed Alcohol Oxidations, J. Am. Chem. Soc.,
38 (2016) 4132-4145.
61] T.R. Porter, D. Capitao, W. Kaminsky, Z. Qian, J.M. Mayer, Synthesis, Radical Reactivity, and
[
[
6
[
1
[
Thermochemistry of Monomeric Cu(II) Alkoxide Complexes Relevant to Cu/Radical Alcohol Oxidation
Catalysis, Inorg. Chem., 55 (2016) 5467-5475.
[
62] M. C. Ryan, L. D. Whitmire, S. D. McCann, S. S. Stahl, Copper/TEMPO Redox Redux: Analysis of PCET
Oxidation of TEMPOH by Copper(II) and the Reaction of TEMPO with Copper(I), Inorg. Chem., 58 (2019)
0194-10200
63] Aleksandra Bocian, Martyna Szymańska, Daria Brykczyńska, Maciej Kubicki,Monika Wałęsa-Chorab,
1
[
Giovanni N. Roviello, Marta A. Fik-Jaskółka, Adam Gorczyński, Violetta Patroniak, New Artificial
Biomimetic Enzyme Analogues Based on Iron(II/III) Schiff Base Complexes: An Effect of (Benz)imidazole
Organic Moieties on Phenoxazinone Synthase and DNA Recognition, Molecules, 24 (2019) 3173-3196.

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Author statement
Conceptualization
Methodology
AG
AG, VP, PP, MM
All authors
All authors
AG, VP, PP, MM
All authors
AG
Formal analysis
Investigation
Resources
Data Curation
Writing - Original Draft
Writing - Review & Editing
Visualization
All authors
All authors
AG, VP, PP, MM
AG
Supervision
Project administration
Funding acquisition
AG

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Conflict of Interest
The authors declare no conflict of interest.

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Graphical abstract

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Highlights
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new benzothiazole Schiff base ligand L and its complexes with copper(II) ions
structures of copper(II) complexes depend on counterion
selective oxidation of benzylic alcohols with TEMPO
proposed reaction mechanism with aid of Density Functional Theory calculations
green chemistry and environmental catalytic process