Solvent-free oxidation of benzyl alcohols catalysed by a tetrazole-saccharinate Zn(II) complex under microwave radiation: The role of the ligand and the reaction mechanism

Article abstract of DOI:10.1016/j.molstruc.2020.128831

Herein we present an efficient methodology for the microwave-assisted peroxidative oxidation of benzyl alcohols to the corresponding aldehydes by using a novel and stable tetrazole-saccharinate zinc(II) catalyst, along with some insights into the reaction mechanism. This methodology is distinguished by the use of easily available and cheap reagents on the genesis of the zinc catalyst, mild reaction conditions, very short reaction periods (5–20 min) and no need to add an organic solvent. Furthermore, the use of TBHP (70percent. aq.) as oxidizing agent turn this protocol a convenient one for benzyl alcohol oxidation in yields up to 98percent.

Full text of DOI:10.1016/j.molstruc.2020.128831

Journal Pre-proof
Solvent-free oxidation of benzyl alcohols catalysed by a tetrazole-saccharinate
Zn(II) complex under microwave radiation: The role of the ligand and the reaction
mechanism
Luís M.T. Frija, André L. Fernandes, M. Lurdes S. Cristiano, Armando J.L. Pombeiro
PII:
S0022-2860(20)31156-X
DOI:
https://doi.org/10.1016/j.molstruc.2020.128831
MOLSTR 128831
Reference:
To appear in: Journal of Molecular Structure
Received Date: 19 May 2020
Revised Date: 29 June 2020
Accepted Date: 3 July 2020
Please cite this article as: Luí.M.T. Frija, André.L. Fernandes, M.L.S. Cristiano, A.J.L. Pombeiro,
Solvent-free oxidation of benzyl alcohols catalysed by a tetrazole-saccharinate Zn(II) complex under
microwave radiation: The role of the ligand and the reaction mechanism, Journal of Molecular Structure
(2020), doi: https://doi.org/10.1016/j.molstruc.2020.128831.
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CRediT author statement
Luís M. T. Frija: Conceptualization, Methodology, Investigation, Writing - Original Draft
André L. Fernandes: Investigation
M. Lurdes S. Cristiano: Supervision
Armando J. L. Pombeiro: Writing - Review & Editing

Solvent-free Oxidation of Benzyl Alcohols Catalysed by
a Tetrazole-saccharinate Zn(II) Complex Under
Microwave Radiation: the Role of the Ligand and the
Reaction Mechanism
[
a]
[b]
Luís M. T. Frija,*
Cristiano
André L. Fernandes,
M. Lurdes S.
[b]
[a]
and Armando J. L. Pombeiro
[a] Centro de Química Estrutural (CQE), Instituto Superior
Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001
Lisbon, Portugal. E-mail: luisfrija@tecnico.ulisboa.pt
[
b] Center of Marine Sciences (CCMar) and Department of
Chemistry and Pharmacy, F.C.T., University of Algarve,
005-039 Faro, Portugal.
8
Graphical abstract
Me H O
2
N
N
O
Me
S
H O
2
N
Zn(II) catalyst
OH
N
N
(
0.1 mol%)
H
Me
O
O2
S
N
Zn
TBHP (2 eq.)
MW
R
N
R
O S
2
*
*
*
Yields up to 98% * Short reaction times (5-20 min.)
N
N
N
N
4
N
TOF's up to 10
* 9 substrates
The catalyst!
Aqueous medium
Me
A
novel, remarkable and stable tetrazole-saccharinate
zinc(II) catalyst promotes the selective peroxidative
oxidation of benzyl alcohols. Mild reaction conditions,
very short reaction periods and aqueous reaction medium,
turn this method
conversion.
a
convenient one for that organic
Keywords: Zinc catalysis • Tetrazole • Saccharin • Benzyl
alcohols • Peroxidative oxidation

Abstract
H
erein we present an efficient methodology for the
microwave-assisted peroxidative oxidation of benzyl
alcohols to the corresponding aldehydes by using a novel
and stable tetrazole-saccharinate zinc(II) catalyst, along
with some insights into the reaction mechanism. This
methodology is distinguished by the use of easily available
and cheap reagents on the genesis of the zinc catalyst,
mild reaction conditions, very short reaction periods (5-20
minutes) and no need to add an organic
solvent.
Furthermore, the use of TBHP (70%. aq.) as oxidizing agent
turn this protocol a convenient one for benzyl alcohol
oxidation in yields up to 98%.
1.
INTRODUCTION
A leading motivation in modern organic chemistry is the
improvement of processes for chemical manipulation, in line
with
the
global
agenda
for
health,
safety
and
sustainability. In this context, the search for more
effective, selective and atom-economical reactions, that
can be conducted under safe and mild conditions persists as
a hot topic of intense research. It is widely known, and
accepted by the generality of the chemical community, that
transition metal catalysts enriched by suitable designed
ligands represent powerful tools for practical catalysis.
However, evidences to the difficulty of use of most of the
applied metals (e.g. Pt, Pd, Ir, Rh) ascend, as a result of
their low abundance, high toxicity and price.[1] Besides,
the regulation of technical protocols to ensure more
ecologically benign routes has been gaining strength,
st
mostly from the beginning of the 21
century.[2] Thus,
contemporary research devoted to the development of new

synthetic methodologies is focused on the replacement of
the classically used precious metals by cheaper and safer
ones. In these circumstances, the use of zinc should be
seriously considered, taking in account its divergent
capabilities,[3] abundance in the earth crust (near 75 ppm,
0.0075%) and biological relevance as an essential trace
element (daily dose for humans 12−15 mg). However, in
contrast to other metals, the use of zinc in catalysis is
still underdeveloped.
In 2013, Enthaler published
article that exposes the applicability of easy accessible
and versatile zinc complexes/salts in homogeneous
catalysis, covering significant group of chemical
a
pleasant perspective
a
reactions, that span along reduction, oxidation and carbon
dioxide functionalization processes.[1] This work boosted
the growing interest in zinc-based catalysts as new tools
for organic synthesis and, in recent years, their potential
was explored in various contexts, but much work remains to
be done in this field.[4–13]
The development of amenable and selective methodologies
for catalytic oxidation of several functional groups is a
topic of notable relevance, due its impact on the
preparation of a large number of added value molecules from
cheap raw materials. In this scenario, selective oxidation
of alcohols to the corresponding carbonyl compounds remains
a hot topic in organic chemistry, both at laboratory and
industrial level.[14-19] For the specific case of benzyl
alcohols, the substrates on focus in this work, several
catalytic systems for their oxidation emerged regularly
along the last years. Recently, we have reported a novel
organocatalyst as an excellent promotor for selective
conversion of
a
series of benzyl alcohols into the
corresponding aldehydes.[20] Proceeding with our efforts
towards the development of new tools for the chemical

modification of benzyl alcohols, herein we disclose
a
relevant improvement on the oxidation of such substrates
mediated by a novel homogeneous Zn(II) catalyst, using
tert-butyl hydroperoxide (TBHP) in aqueous medium.
2.
EXPERIMENTAL
2.1. Materials and methods
Unless otherwise noted, solvents and starting materials
were obtained from Aldrich. All chemicals used were of
reagent grade without further purification before use.
Column chromatography was performed using silica gel 60 MN
and aluminium-backed silica gel Merck 60 F254 plates were
used for analytical thin layer chromatography (TLC).
1
13
Melting points were recorded and are uncorrected. H and
C
NMR spectra were recorded at room temperature on a Bruker
Avance II 300 (UltraShield™ Magnet) spectrometer operating
1
13
at 300 MHz ( H) and 75 MHz ( C). The chemical shifts are
reported in ppm using TMS as internal standard. Carbon,
hydrogen and nitrogen elemental analyses were carried out
by the Microanalytical Service of the Instituto Superior
–
Técnico – University of Lisbon. FT-IR spectra (4000-400 cm
1
)
were recorded on a VERTEX 70 (Bruker) spectrometer using
KBr pellets. Mass spectra were obtained on a VG 7070E mass
spectrometer by electron ionization (EI) at 70 eV.
The catalytic tests under microwave irradiation (MW) were
performed in a focused Anton Paar Monowave 300 microwave
reactor using a 10 mL capacity reaction tube with a 10 mm
internal diameter, fitted with a rotational system and an
IR temperature detector.
Chromatographic analyses were performed in
Instruments GC 8000 series gas chromatograph with a DB-624
J&W) capillary column (DB-WAX, column length: 30 m;
a
Fisons
(
internal diameter: 0.32 mm), FID detector and the Jasco-
Borwin v.1.50 software; [GC conditions: Tinjection = 240 °C;

–
Tinitial = 140 °C (1 min) raised 10 °C min 1 to 220 °C (1
min.); carrier gas: He]. The internal standard method was
used to quantify the organic products.
2.2. Preparation of the saccharyl building block
The saccharyl building block, saccharyl chloride (2), was
synthesized from commercially available saccharin, through
halogenation. 3-Chloro-1,2-benzisothiazole-1,1-dioxide (1)
was obtained from saccharin (10.2 g; 56 mmol) and
phosphorus pentachloride (14.0 g; 66 mmol) heated at 180
°
C, using a procedure previously reported;[21] colorless
–1
needles (7.00 g; 63% yield); m.p. 143–145 °C; IRνmax (cm ):
1
724, 1654, 1603 (C═C), 1346 (SO ), 775 (Ar─H) and 692
2
1
(C─Cl);
H
NMR (CDCl ):
δ
7.72-7.91 (m, 4H, Ar─H);
3
elemental analysis: C 41.5%, H, 2.0%, N, 6.9% (found), C,
41.7%, H, 2.0%, N, 7.0% (calculated for C H NO SCl); MS
7 4 2
+
(
EI): m/z 201 [M ].
2.3. Preparation of the tetrazolyl building block 4a
[Tetrazolyl derivative 4a was prepared from commercially
available 5-aminotetrazole monohydrate through methylation.
This reaction produces mixture of 1-methyl-(1H)-
a
tetrazole-5-amine and 2-methyl-(2H)-tetrazole-5-amine. The
regioisomers have different solubility and are separated
during work-up, as described below.]
A
solution of sodium hydroxide (20% w/v) was added
dropwise to a suspension of 5-aminotetrazole monohydrate
10.3 g; 0.1 mol) in water (30 mL), with a drop of
(
phenolphthalein. The mixture was stirred until complete
dissolution of the suspended material. Dimethyl sulfate (20
mL; 0.11 mol) was then added in small portions, keeping an
alkaline medium
through addition of aqueous
sodium
hydroxide. The final mixture was refluxed for 1 h, then
cooled, and finally left in an ice bath, in the fridge, for

2
days. Colorless needles of 1-methyl-(1H)-tetrazole-5-
amine (4b) were filtered, (6.1 g; 51% yield), m.p. 220–221
1
+
°
C, H NMR (CDCl ): δ 4.15 (s, 3H), MS (EI): m/z 99 [M ].
3
The filtrate collected was evaporated under reduced
pressure to afford a solid residue. Water (50 mL) was
added, and the mixture was then extracted with diethyl
ether (3 × 50 mL). The organic extract was dried over
anhydrous sodium sulfate, filtered and the filtrate
evaporated to afford white crystals. Recrystallization from
diethyl ether gave 2-methyl-(2H)-tetrazole-5-amine (4a) as
colorless needles (3.0 g, 25% yield), m.p. 104.5–105.5 °C,
1
+
H NMR (CDCl ): δ 3.32 (s, 3H), MS (EI): m/z 99 [M ].
3
2.4. Preparation of the 2-Methyltetrazole-saccharinate 5
A mixture of 2-methyl-(2H)-tetrazole-5-amine (0.25 g;
2.56 mmol) and 3-chloro-1,2-benzisothiazole 1,1-dioxide
(0.53 g, 2.56 mmol) in dry THF (20 mL) was stirred at 60 °C
during 24 h under a nitrogen atmosphere. The solvent was
then evaporated under reduced pressure and the remaining
solid was washed with acetone, dried under vacuum at room
temperature
and
recrystallized
from
a
mixture
of
acetone/ethanol (1:1) to give the required product as
1
colorless crystals (0.48 g; 72% yield), m.p. 285–286°C,
H
NMR (DMSO): δ 8.49–8.50 (m, 1H), 8.10–8.13 (m, 1H), 7.90–
+
7
.92 (m, 2H), 4.42 (s, 3H), MS (EI): m/z 250 [M ].
2
.5. Preparation of the zinc complex 6
To 10 mL methanol/dimethyl
DMSO)/dichloromethane (CH Cl ) solution
-methyltetrazole-saccharinate 5 (250 mg; 1.0 mmol) was
a
sulfoxide
(1:2:2) of
(
2
2
2
added ZnSO ∙H O (179.5 mg; 1.0 mmol) and the reaction
4
2
mixture was stirred for 1h at room temperature until
complete dissolution of the solids. The resulting colorless

solution was kept in open air at room temperature for
crystallization. After days, single white crystals
8
suitable for X-ray diffraction were isolated, [270 mg; 38%
yield; (76% yield based on ligand 5)]. Elemental analysis
(
%): C, 34.04, H, 3,45, N, 23.81 (found); C, 34.02, H,
,43, N, 23.80 (calculated for C H N O S Zn). IR (KBr;
3
20 26 12 7 3
−1
cm ): 3455 ν(OH), 1615, 1570, 1417, 1283 ν(C–N), 1245,
152 ν(S═O), 1001, 955.
1
2
.6. Catalytic assays via MW irradiation
Experiments with 2.5 mmol of substrates and 2.5-7.5 mmol
of oxidant were conducted using focused Anton Paar
Monowave 300 microwave reactor in 10 mL glass vessels with
0 mm internal diameter, sealed with rubber membranes in a
a
1
stirred mode with simultaneous cooling (IR temperature
detector). The targeted temperature together with a maximum
microwave power (50 or 100 W) was set. The targeted
temperature was reached within a few minutes. During the
course of the reaction, the microwave power (15-50 W) as
well as the pressure (1 to 10 bar) varied. At the end of
the reaction, the mixture was cooled down to room
temperature and the vessel cap was carefully opened to
slowly release the pressure.
2.7. Gas-chromatography analysis
Succeeding the MW-assisted reaction, 7 mL of acetonitrile
together with acetophenone (1.25-2.50 mmol; internal
standard) were added to the reaction mixture. A final
solution aliquot (1 mL) was removed and centrifuged, and
the supernatant was analyzed by GC for quantification of
oxidation products.
2.8. X-ray measurements

X-ray quality single crystals of complex 6 were immersed
in cryo-oil, mounted in Nylon loops and measured at a
temperature of 296-297 K. Intensity data were collected
using a Bruker AXS-KAPPA APEX II PHOTON 100 diffractometer
with graphite monochromated Mo-Kα (λ = 0.71073) radiation.
Data were collected using omega scans of 0.5° per frame and
full sphere of data were obtained. Cell parameters were
retrieved using Bruker SMART[22] software and refined using
Bruker
SAINT[23]
on
all
the
observed
reflections.
Absorption corrections were applied using SADABS.[24]
Structures were solved by direct methods by using SIR-
9
7[25] and refined with SHELXL–2014.[26] Calculations were
performed using the WinGX-Version 2014.01.[27] The hydrogen
atoms attached to carbon atoms were inserted at
geometrically calculated positions and included in the
refinement using the riding-model approximation; Uiso(H)
were defined as 1.2 Ueq of the parent carbon atoms for
phenyl residues and 1.5 Ueq of the parent carbon atoms for
the methyl groups. The hydrogen atoms of water molecules
were located from the final difference Fourier map and the
isotropic thermal parameters were set at 1.5 times the
average thermal parameters of the belonging oxygen atoms.
Least square refinements with anisotropic thermal motion
parameters for all the non-hydrogen atoms and isotropic for
the remaining atoms were employed.
3. RESULTS AND DISCUSSION
3
.1. Synthesis of the 2-methyltetrazole-saccharinate
5) and Zn(II) complex (6)
The production of tetrazole-saccharinate bidentate
(
N,N-chelating ligands was initiated by some of us,
about a decade ago.[28] The synthetic approach used
for the preparation of this kind of scaffolds, and

applied for the particular case of compound 5,
consists in a convergent strategy involving a first
derivatization of the heterocyclic cores (tetrazole
and benzisothiazole) independently, followed by the
coupling of the two entities (see Figure 1). Synthetic
details on the preparation of 5 should be consulted in
the Experimental section.
Contrary to the ligand 5, the Zn(II) complex (6,
Figure 1) is absolutely new and reported here for the
first time. The synthesis of the Zn(II) metal complex
comprising ligand 5 proceeded at ambient conditions by
reaction of 5 with ZnSO ∙H O salt. Metal complex 6 was
4
2
isolated as
methyltetrazole-saccharinate
bidentate N,N-chelating ligand
crystalizes with one water molecule as solvent of
a
mononuclear compound where the 2-
acts as monoanionic
(Figure 1) and
5
crystallization. The central zinc atom of
hexacoordinated with distorted octahedral
6
is
a
N4O2
coordination. There are two monoanionic bidentate N,N-
ligands, one water and one DMSO molecules coordinated
to Zn(II) ion. Detailed structural data for complex 6
can be accessed in Tables S1-S3 in Supporting
Information.
<
Figure 1. Synthetic approach used in the production of complex 6.>
3.2. Application of Zn(II) complex (6) as catalyst for
benzylic alcohols oxidation
Having the complex 6 in hand, a careful optimization of the
reaction conditions using microwave reactor was
a
initialized. Electing the benzyl alcohol (7a) as model
substrate, a screening covering a number of variations on
reaction times and temperatures, MW-power, catalyst loading
and the presence of additives, was completed (see Table 1).

<
Table 1>
To our delight, in first instance, it was observed that,
for the alcohol 7a, the use of a very low amount of Zn(II)
catalyst (0.1 mol%) at relatively low temperature (70°C,
aprx. 15-25W MW power) and in a short reaction period (10
min.), had led to the selective formation of benzaldehyde
(
8a) in nearly quantitative yield. The use of TBHP (70% in
H2O) as oxidant (2.0 eq.), revealed to be the best choice
along the tested possibilities (see Table 1). It should be
noted that, per se, the salt ZnSO ∙H O used in the
4
2
production of complex 6, had shown important catalytic
activity in the oxidation of the alcohol 7a; patently lower
than the catalytic activity of complex 6 under similar
conditions, but nonetheless noteworthy (Table 1, entries 1
and 23).
Subsequently to the optimization of reaction conditions
comprising the alcohol 7a, the scope for the oxidation was
evaluated using a series of benzyl alcohol derivatives (7b-
i, Table 2). Characteristic substrates bearing different
substituent groups at the benzene ring were submitted to
similar reaction environments based on the earlier results
for 7a, to produce the corresponding aldehydes in excellent
yields
(Table
2).
Ordinarily,
for
all
the
tested
substrates, the oxidation occurs in very short periods of
time (5-20 min.) at temperatures not exceeding 100°C
(usually 70°C) featuring high turnover frequencies (TOFs)
up to
4
-1
1
.1 × 10 h .
Further, the introduction of the nitroxyl radical
,2,6,6-tetramethylpiperidyl-1-oxyl (TEMPO) in the system
2
with the alcohol 7a leads to an obvious decrease of
reaction yield (Table 2, entries 1 and 5). As indicated by
us in preceding investigations,[19a] and assuming
a
presumable similar effect herein, TEMPO could act as a

radical trap reacting with free radical species generated
form TBHP (tert-butoxyl and hydroxyl radicals) to form
other peroxides. Besides, the addition of the carbon-
radical trap CBrCl3 to the system created
a
strong
inhibitory effect on the reactivity, reflected in a very
low yield (22%) achieved (Table 2, entry 6). Given these
circumstances, the tests carried out with TEMPO and CBrCl3
indicate that the oxidation of benzyl alcohols using TBHP
and catalysed by the zinc complex 6 might proceed via a
radical mechanism involving oxygen- and carbon-centered
radicals.
3.3. Reaction mechanism survey
The improvement in the catalytic activity when the zinc
coordinates with two ligands 5, forming the complex 6, is
evident, comparatively to the observed activity when the
metal is used in the salt formulation ZnSO ∙H O. The role
4
2
of the ligands
5
on the promotion of benzyl alcohol
oxidation process seems to be irrefutable. What remains to
be clarified is if such ligands act independently to the
metallic center during the catalytic cycle, or if they are
acting simply through an electronic stabilization of the
zinc, or if a cooperative metal-ligand mechanism is at
place.
We know that ligand 5, by itself, works as
a
promoter/organocatalyst in the oxidation of a series of
benzyl alcohol derivatives, although showing modest results
in terms of reaction yields when compared with catalyst
6
.[20]
In the course of this investigation, the detection of
free ligand 5, i.e., non-coordinated to zinc, after work-
up, was never feasibly in any circumstance, largely due to
the small amount of catalyst used in each reaction.
Nevertheless, although this possibility cannot be ruled

out, its effect is not
a
determinant one, since the
catalytic activity of complex 6 is markedly higher than
that of the free ligand.[19e]
In this context, an initial displacement of the labile
st
water molecule from the complex 6 (1 step) should conduct
nd
to the coordination of benzyl alcohol to zinc (2
step),
forming the new complex 6’.
In a parallel process, the TBHP present in the reaction
medium will decompose to form tert-butoxyl and hydroxyl
radicals,[29a-b] via homolytic cleavage of O–O bond
promoted by microwave radiation.[29b-c] It is assumed that
TBHP-based
radicals’
formation
should
occur
without
intervention of the Zn(II) complex (6).
The 3rd step of the catalytic cycle will comprise the
liberation of the hydroxyl proton from the alcohol and its
transfer to a basic nitrogen atom of one of the ligands 5
(see Figure 2, structure 6’’), followed by the abstraction
of a C–H hydrogen atom by tert-butoxyl radical releasing
tert-butanol and generating the transition state structure
TS1 (step 4). In the final steps, the reaction of TS1 with
a hydroxyl radical liberates water and the corresponding
aldehyde, leading to the regeneration of the catalyst 6,
enabling turnover.
The tetrazole-saccharinate ligand, in view of its
basicity, conceivably promotes proton-shift steps, namely
accepting the acidic proton from the coordinated alcohol
(
step 3) and releasing it (step 5) for the formation of
water and aldehyde with regeneration of 6. Hence, a metal-
ligand cooperation effect is proposed to occur in this
system.
<
Figure 2. Proposed catalytic cycle for the oxidation of benzyl
alcohol 7a promoted by complex 6.>

Additional investigations on other zinc catalysts, as
well as extensive mechanistic studies (involving DFT
calculations) on the oxidation of benzyl alcohols mediated
by the present
zinc complex,
are ongoing
in our
laboratories and will be reported in due course. It is
estimated that some of this research may clarify the
potential metal-ligand cooperation during the catalytic
cycle.
4. CONCLUSIONS
In conclusion, we have shown herein
a
facile and
selective transformation of a series of benzyl alcohols to
the corresponding aldehydes promoted by a novel tetrazole-
saccharinate Zn(II) catalyst. The reaction, activated by
microwave radiation, proceeds typically in a few minutes
under effective smooth conditions by using TBHP (70%. aq.)
as oxidizing agent, in absence of any organic solvent and
conveys
experiments allude to
comprising oxygen- and carbon-centered radicals.
some
functional
group
tolerance.
Current
a
radical reaction
mechanism
The use of zinc catalysts, particularly on oxidation
reactions comprising different functional groups present in
relevant small organic molecules, although less frequent
when compared to copper or iron catalysts is growing
significantly with good results. Evidence of this is the
research work offered here!
ACKNOWLEDGEMENTS
This work was partially supported by the Fundação para a
Ciência
e
Tecnologia
(FCT),
Portugal,
project
UIDB/00100/2020 of Centro de Química Estrutural, and

project UID/MULTI/04326/2019 of Center of Marine Sciences
CCMAR). L.M.T.F. expresses gratitude to FCT for the work
(
contract nº IST-ID/115/2018.
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1
Supporting Information
Structural data for all the isolated compounds and selected
structural data of X-ray structure of complex 6. CCDC number
1
962832 for complex 6 (Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif).

Table 1. Screening of the optimal reaction conditions for benzyl
a
alcohol oxidation.
Catalyst 6 amount
Reaction
time (min.)
T
b
Entry
(mol%)
0.1
0.2
0.1
0.1
Oxidant
TBHP
TBHP
TBHP
TBHP
TBHP
Additive
(°C)
70
70
70
100
70
Yield (%)
1
-
-
-
-
10
10
30
5
95
93
89
84
63
c
2
3
c
4
5
0.1
TEMPO
10
(
5 µmol)
6
0.1
TBHP
CBrCl3
10
70
45
(
1 mmol)
-
CBrCl3
c
7
0.3
0.1
TBHP
TBHP
10
10
70
70
91
22
8
(
2.5 mmol)
TEMPO
9
0.1
TBHP
10
70
35
(
50 µmol)
d
1
1
1
1
1
1
1
1
1
1
0
1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
TBHP
TBHP
TBHP
TBHP
TBHP
-
-
-
-
-
-
-
-
-
-
10
10
10
5
10
5
70
70
50
72
96
71
85
95
80
73
82
55
36
e
2
3
4
5
6
7
8
9
70
120
120
150
70
70
70
TBHP
TBHP
3
H O (50%)
10
10
10
2
2
t
BuOK
SO HO K
3
3
(4.5% active oxygen)
2
2
0
1
0.1
-
0.1
0.1
Oxone®
TBHP
-
-
-
-
-
10
10
10
10
70
70
70
70
41
22
14
43
f
2
2
g
2
3
TBHP
(
ZnSO ∙H O)
4 2
a
Reaction was carried out with 2.5 mmol of benzyl alcohol (7a), TBHP (2.0 eq., 70 % in H O), in a MW
2
reactor at different temperatures (power range: 20-50 W) and reaction time, without adding extra
solvent.
b
Isolated yield.
Determined by GC.
Reaction with 1.0 eq. of TBHP.
Reaction with 3.0 eq. of TBHP.
Reaction performed in distilled water (0.5 mL).
Reaction with ZnSO ∙H O as catalyst.
c
d
e
f
g
4
2

Table 2. Substrate scope for the microwave-assisted oxidation of
[
a]
benzyl alcohols promoted by the zinc complex 6
[
c]
Entry
Alcohol
t
T
(°C)
Yield
(%)
TON
[
b]
-1 [d]
(
min.)
TOF (h )
1
10
7
0
70
70
100
70
70
95
950
3
7
a
(5.7 × 10 )
930
[
e,f]
2
3
4
5
7a
7a
7a
7a
10
30
5
93
89
84
63
22
3
(5.6 × 10 )
[
f]
890
3
(1.8 × 10 )
840
4
(1.0 × 10 )
[
f,g]
10
10
630
3
(3.8 × 10 )
[
h]
7a
220
6
7
3
(1.3 × 10 )
15
70
90
900
(3.6 × 10 )
3
7b
8
9
5
70
70
98
85
980
(1.2 × 10 )
4
7c
15
850
3
(3.4 × 10 )
7d
10
20
100
82
820
3
(2.5 × 10 )
7e
1
1
2
10
10
70
70
87
75
870
3
(5.2 × 10 )
7f
1
750
3
(4.5 × 10 )
7
g
h
1
3
10
70
70
64
87
640
3
(3.8 × 10 )
7
10
870
5.2 × 10 )
14
15
16
3
(
7
i
[
i]
i]
7a
7a
(16h)
30
reflux
reflux
45
19
450
28)
(
[
190
380)
(
[
a] Reactions were carried out with a benzylic alcohol 7 (2.5 mmol), zinc
complex 6 (0.1 mol%) and TBHP (2.0 eq., 70 % in H O) in a microwave
reactor (15-25 W) at a determined temperature without adding extra solvent.
b] Isolated yield. [c] TON: Turnover number. [d] TOF = TON.h–1. [e] 0.2
mol% of 6. [f] Determined by GC. [g] With additive TEMPO (5.0 µmol). [h]
With CBrCl (2.5 mmol). [i] Reaction mixture heated in an oil bath.
2
[
3

Figure 1. Synthetic approach used in the production of complex 6.

Figure 2. Proposed catalytic cycle for the oxidation of benzyl alcohol
a promoted by complex 6.
7

Highlights:
•
•
•
•
Synthesis and structure of an original tetrazole-
saccharinate Zinc(II) catalyst
Effective microwave-assisted peroxidative oxidation of
benzyl alcohols
Environmental benign methodology proceeding in absence of
organic solvent
Potential radical reaction mechanism comprising oxygen- and
carbon-centered radicals

Declaration of interests
☒
The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐
The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: