Electrochemical oxidations of thioethers: Modulation of oxidation potential using a hydrogen bonding network

Article abstract of DOI:10.1016/j.elecom.2019.106583

A highly efficient chemo-selective electrochemical oxidation of thioethers to sulfoxides and sulfones was developed. The hydrogen bonding network generated from hexafluoro-2-propanol (HFIP) and acetic acid (AcOH) plays an important role in the modulation of oxidation potential. The hydrogen bonding network complexes strongly with the sulfoxide, making it less prone to further oxidation. Therefore, thioethers can be selectively electrochemically oxidized to sulfoxides and over-oxidization could be minimized. Moreover, this modulation of oxidization via hydrogen bonding was supported by density functional theory (DFT) calculations and cyclic voltammetry experiments.

Full text of DOI:10.1016/j.elecom.2019.106583

Journal Pre-proofs
Electrochemical oxidations of thioethers: Modulation of oxidation potential us-
ing a hydrogen bonding network
Shiwen Liu, Bocheng Chen, Yi Yang, Yuhao Yang, Qianjin Chen, Xiaojun
Zeng, Bo Xu
PII:
S1388-2481(19)30246-2
DOI:
https://doi.org/10.1016/j.elecom.2019.106583
ELECOM 106583
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Electrochemistry Communications
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Revised Date:
Accepted Date:
12 September 2019
25 October 2019
28 October 2019
Please cite this article as: S. Liu, B. Chen, Y. Yang, Y. Yang, Q. Chen, X. Zeng, B. Xu, Electrochemical oxidations
of thioethers: Modulation of oxidation potential using a hydrogen bonding network, Electrochemistry
Communications (2019), doi: https://doi.org/10.1016/j.elecom.2019.106583
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Electrochemical oxidations of thioethers: Modulation of
oxidation potential using a hydrogen bonding network
a
b,
b
b
b
Shiwen Liu , Bocheng Chen Yi Yang , Yuhao Yang , Qianjin Chen , Xiaojun
Zeng b *, Bo Xu b *
a College of Textiles and Clothing, Yancheng Institute of Technology, Yancheng,
224051, China.
b Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education,
College of Chemistry, Chemical Engineering and Biotechnology, Donghua
University, Shanghai 201620, China.
*Corresponding authors
Email: bo.xu@dhu.edu.cn, xjzeng1004@hotmail.com
Abstract
A highly efficient chemo-selective electrochemical oxidation of thioethers to
sulfoxides and sulfones was developed. The hydrogen bonding network generated
from hexafluoro-2-propanol (HFIP) and acetic acid (AcOH) plays an important role in
the modulation of oxidation potential. The hydrogen bonding network complexes
strongly with the sulfoxide, making it less prone to further oxidation. Therefore,
thioethers can be selectively electrochemically oxidized to sulfoxides and
over-oxidization could be minimized. Moreover, this modulation of oxidization via
hydrogen bonding was supported by density functional theory (DFT) calculations and
cyclic voltammetry experiments.
Keywords
Hydrogen boding network; electrochemical oxidation; sulfoxides and sulfones;
thioethers
1

1. Introduction
Oxidation is ubiquitous in organic synthesis, and electrochemical oxidations are
considered as more atom-economic and more sustainable oxidation methods
compared to chemical oxidations [1-3]. However, overoxidation may happen if the
desired oxidation product could be further oxidized. We envision that a strong
hydrogen bonding donor system could be used to modulate oxidation and minimize
over-oxidation (Figure 1. a). Generally, a new oxygen atom could be introduced into
an organic molecule which was oxidized. And this oxygen may function as hydrogen
bonding acceptor. Thus, a hydrogen bonding complex may form via a strong
interaction between hydrogen bonding acceptor (the oxygen atom) and a hydrogen
bonding donor such as hexafluoro-2-propanol (HFIP) [4]. For example, Bégué and
coworkers [4] have reported that the oxidation of sulfides into sulfoxides by aqueous
30% H2O2 in HFIP. The hydroxyl proton of HFIP could form a strong hydrogen bond
with H2O2, activating the hydroxyl leaving group (H2O2), which promoted the
oxidation of sulfides into sulfoxides. On the other hand, the nucleophilicity of the
sulfur atom decreased significantly due to the formation of a strong hydrogen bond
between HFIP and the oxygen of the sulfoxides, which prevented further oxidation
into sulfone. Thus, the hydrogen bonding donor will deprive some electron density of
the H-bond acceptor and make it less prone to be oxidized. By doing this,
over-oxidation could be reduced. If the further-oxidation products are desired, a
relatively high voltage could be employed.
Recently Hunter and coworkers have reported that a linear H-bond aggregate is a
much better H-bond donor system than monomer and cyclic H-bond aggregates [5]
(Figure 1. b). In general, acetic acid is not a good hydrogen bond donor because it
often forms a cyclic dimer in solutions of non-hydrogen-bonding solvents [6]. We
envision that cyclic dimer of acetic acid could be converted to linear aggregates when
interacting with strong H-bond donor solvents such as HFIP and generate a linear
H-bond aggregate with a very high H-bond acidity (Figure 1. b). Moreover, this strong
2

H-bond network could be used in the modulation of oxidation of H-bond acceptors. Our
proof of concept application is chemo-selective oxidation of thioethers to sulfoxides
and sulfones (Figure 1. d). We envision that thioethers could be selectively oxidized in
the presence of a hydrogen bonding network generated from HFIP and acetic acid.
Transitionally, the most common and straightforward method for the preparation
of sulfoxides and sulfones is the oxidation of thioethers. Indeed, many chemical
oxidation systems such as hydrogen peroxide [4, 7-18], peroxycarboxylic acid [19]
and many other oxidants [20-25] have been reported. Unfortunately, these strategies
typically suffer from selectivity issues, e.g. over-oxidation of the sulfoxide to the
sulfone or oxidation of other functional groups within the molecule. Electrochemical
anodic oxidation presents a powerful and environmentally friendly method to the
synthesis of desirable products, which has gained increasing attention [26-35]. Noël
reported selective electrochemical oxidation of sulfides [36, 37] using a
continuous-flow microreactor, providing an environmentally benign method for the
synthesis of sulfoxides and sulfones. However, low to moderate yields are obtained
for the oxidation of sulfides into sulfoxides and tuning the voltage over the electrodes
is the only way to avoid over-oxidation. Huang and coworkers [38] demonstrated an
electrochemical synthesis of sulfoxides from thiols, but this approach is limited to the
preparation of methyl sulfoxides. Herein, we are glad to report a highly efficient
electrocatalytic protocol for chemo-selective oxidation of thioethers to sulfoxides and
sulfones based on hydrogen bonding modulation (Figure 1. d).
2. Results and discussion
Initially, we started this selective oxidation by using thioether 1a as a model
substrate (Table 1). Utilizing the common Pt (platinum) as electrodes, LiClO4 as the
electrolyte, and acetonitrile (MeCN) as solvent under constant potential, 5% desired
product 2a was obtained (Table 1, entry 1). Similarly, there was no reaction when
polar aprotic solvent – DMF (N, N-dimethylformamide) was used (Table 1, entry 2).
And our DFT calculations are consistent with our hypothesis that hydrogen bonding
may increase the oxidation potential (Figure 1. c). In general, the oxidation potential
3

is directly related to ionization potential [39]. Ionization potential increases
significantly when bonding with an increased number of hydrogen bonding donors,
especially bonding with HFIP. For example, a sulfoxide forms an H-bond complex
with an increasing number of acetic acid or HFIP and its ionization potential indeed
increases (Figure 1. c), which would make further oxidation of sulfoxides to sulfones
difficult. HFIP has been extensively used as an extraordinary solvent in promoting
various chemical transformations [4, 40-48]. Owing to its exceptional redox stability,
HFIP has been commonly used in electrochemistry [49-56]. However, there was no
reaction when using HFIP as the solvent in this case (Table 1, entry 3). Then we
tested various other hydrogen bonding donor solvents (methanol, acetic acids and
water) (Table 1, entries 4-6). Moderate yields were observed when methanol or acetic
acid was used. We envisioned that in a pure liquid phase, a mixture of acetic acid and
HFIP might function as a very strong hydrogen bonding donor network. To our
delight, the oxidation was very efficient using a mixture of HFIP/AcOH (1:1) as the
solvent (Table 1, entry 7). What’s more, there was almost no overoxidation product
3a. However, a mixture of HFIP and methanol was not effective (Table 1, entry 8).
After accessing sulfoxides efficiently, we next focused on the investigation of
oxidation of thioethers into sulfones. Firstly, 2 equivalents of nBu4NBF4 were used as
electrolytes, but poor yield was obtained by increasing the voltage from 3 V to 4 V
(Table 1, entry 9) and no product 3a was observed when changing solvent into acetic
acid (Table 1, entry 10). Further screening of electrolytes showed that LiClO4 as an
electrolyte was superior to nBu4NPF6 on both selectivity and conversion (Table 1,
entries 11 - 12). As expected, this oxidation reaction could not proceed without
electricity (Table 1, entry 13).
With the optimized reaction conditions in hand, we started to examine the scope
of substrates (Figure 2). Firstly, diverse thioanisole derivatives could be selectively
oxidized into sulfoxides (2a-2o) in good to excellent yields. The substitution pattern
(meta, para) and electronic properties of aromatic substituents (electron-deficient or
rich) of thioanisole had little effect on this transformation (2a-2o). The only exception
4

was the oxidation of aniline derivative (2l). A relatively low yield was obtained even
decreasing the voltage. By careful observation and study, we found that a layer
polymer film was deposited on the electrodes, which made electrodes inactive and
prevented further reaction (reduced current) . Besides, diaryl sulfides (2p – 2t) were
also suitable substrates and good yields could be obtained in all cases. Then, sulfides
containing various functional groups such as ester (2u), ether (2v), ketone (2w),
alkyne (2x), alkene (2y, 2z) and cyclopropane (2aa) were explored under optimized
conditions, affording moderate to good isolated yields with satisfactory tolerance.
Additionally, this protocol also tolerated dialkyl sulfides and sulfides containing
natural product skeletons (2ab – 2ad), giving good chemical yields. At last, the
chemoselectivity of this method was investigated in the oxidation of sulfides
containing two different sulfur moieties (2ae, 2af). Clearly, the sulfur with high
electron density was oxidized preferably (2ae). Moreover, sulfide moiety could be
oxidized for a compound containing sulfide and thiophene (2af).
We then turned our attention to the investigation of over oxidation of thioethers
to access sulfones 3 (Figure 3). The conditions were similar except increasing voltage
(4 V vs. 3 V) and slightly prolonging the reaction time. The conditions worked well
for diverse thioethers (3a – 3r). Similarly, the substitution pattern (meta, para) and
electronic property of substituents (electron-deficient or rich) on aromatics had little
effect on chemical yields (3a-3k). Moreover, the conditions also worked well for
diaryl thioethers (3n, 3m) and dialkyl thioethers (3q, 3r) with good functional groups
tolerance. It should be noted that disulfides could be also oxidized into sulfones under
optimized conditions [57] (3s – 3u). Furthermore, both dialkyl disulfide (3s, 3u) and
diaryl disulfide (3t) were suitable substrates. In Noël’s work [37], tuning the voltage
over the electrodes was the only way to avoid over-oxidation. This protocol
introduced the hydrogen bonding network into electrochemical oxidations of
thioethers for the first time. The hydrogen bonding between HFIP and the sulfoxide
made it less prone to further oxidation. Therefore, thioethers can be selectively
electrochemically oxidized to sulfoxides and over-oxidization could be avoided under
optimized conditions.
5

Next, electro-oxidative synthesis of unsymmetrical disulfides from thiols was
explored (Figure 4). This electrooxidation has been achieved by Lei and coworkers
using a polar aprotic solvent – DMF [58], but their system did not give good yields
for electron-deficient substrates such as para-nitro-thiophenol and also aliphatic thiols
with small steric hindrance. To our delight, our protocol worked very well for both
electron-rich and poor thiophenols without the formation of the homodisulfides. We
speculated that unsymmetrical S-S bond formation can be achieved by utilizing the
difference of the oxidation potential between the aromatic thiol and the alkyl thiol.
We then moved our focus to the investigation of reaction pathways. The reaction
was not affected by the argon atmosphere (Figure 5a). Moreover, the reaction was
also not affected in the presence of TEMPO (2, 2, 6, 6-tetramethylpiperidine-1-oxyl, a
radical quencher) (Figure 5b). These results indicated that O2 in the air was not the
source of the oxygen atom. We envisioned that the possible source of oxygen atom
was from water present in the reaction mixture. Thus, we conducted various reactions
by addition of H2O18. In the presence of 5 equivalents of H2O18, the sulfoxide product
2f containing a significant proportion of O18 (53%) (Figure 5c) was observed. For the
preparation of sulfone 3f, a large proportion of O18 was also observed in sulfone
product 3f (Figure 5d). For synthesis of sulfone, we also conducted the reaction
stepwise (Figure 5e). In the first stage, a low voltage was used in the absence of H2O18,
in stage 2, we increased the voltage and added 10 equivalents of H2O18. In the end, we
obtained a mixture of the 3f-1 and 3f-2 and 3f-3. This result indicated that reaction
proceeded in a stepwise manner and the oxygen source for oxidation sulfoxide to
sulfone was also from water.
Additionally, cyclic voltammetry (CV) experiments were conducted to study the
redox potential of the substrates (Figure 6). The oxidation potential of thioether 1a
and the corresponding sulfoxide 2a in the presence of LiClO4 were measured by using
acetonitrile and H-bond network (HFIP/AcOH) as solvents respectively (Figure 6). To
avoid over-oxidation, the difference or gap between oxidation potential of 1a and
oxidation potential of 2a (ΔV) should be as big as possible. It was observed that both
the onset potentials for oxidation of thioester substrate 1a (Figure 6B, curve b, 1.13 V)
6

and sulfoxide (Figure 6B, curve c, 1.88 V) in the H-bond network solvent were lower
than that in acetonitrile (Figure 6A, curve b, 1.37 V and curve c, 1.94 V). Thus the ΔV
was significantly larger when HFIP/AcOH was used as the solvent (0.75 V vs. 0.57
V), enabling better control of electrooxidation of thioesters.
Lastly, our methodology can be used in larger-scale synthesis without
complications (Figure 7). Without any protection, using the common Pt anode and
cathode, 1f could be selectively oxidized to 2f and 3f in gram scale.
3. Conclusions
In conclusion, we have developed a highly efficient and oxidant free
electrocatalytic protocol for selective oxidation of thioethers to sulfoxides and
sulfones by using a hydrogen bond network system.
Conflict of interest
There is no conflict of interest.
Acknowledgments
We are grateful to the National Science Foundation of China for financial support
(NSFC-21672035).
Appendix A. Supplementary data
Supplementary data to this article can be found online at ….
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in oxidative cross-coupling of aryls by solvent effect of 1,1,1,3,3,3-hexafluoropropan-2-ol, Chem. Eur.
J., 21 (2015) 12321-12325.
[53] S. Lips, D. Schollmeyer, R. Franke, S.R. Waldvogel, Regioselective metal- and reagent-free
arylation of benzothiophenes by dehydrogenative electrosynthesis, Angew. Chem. Int. Ed., 57 (2018)
13325-13329.
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bond formation, Angew. Chem. Int. Ed., 55 (2016) 9437-9440.
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solvent-directed stereoselective and electrocatalytic synthesis of diisoeugenol, Chem. Commun., 54
(2018) 2771-2773.
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[58] P. Huang, P. Wang, S. Tang, Z. Fu, A. Lei, Electro-oxidative S−H/S−H cross-coupling with hydrogen
evolution: facile access to unsymmetrical disulfides, Angew. Chem. Int. Ed., 57 (2018) 8115-8119.
11

FIGURE CAPTIONS
Figure 1. Literature background.
Figure 2. Scope for the synthesis of sulfoxides 2.
Figure 3. Scope for the synthesis of sulfones 3.
Figure 4. Scope for the synthesis of unsymmetrical disulfides.
Figure 5. Investigations of reaction pathways.
Figure 6. Cyclic voltammetry at a 3 mm diameter Pt electrode.
Figure 7. Gram scale synthesis.
TABLE CAPTIONS
Table 1. Optimization of reaction conditions.
12

a)
H-bond donor
system
R
H O
low voltage
high voltage
electrical
oxidation
no over-oxidation
further oxidation
R
O
X
O
X
H O
X
R2
R1
R2
R2
R1
R1
1
X = heteroatom (e.g. S)
b)
H
CF3
CF3
O
H
strong H-bond donor system
O
O
m
n
linear H-bond network or aggregates
c)
H
H
AcO
H
AcO
H
O
O
H
O
O
S
O
S
O
S
O
S
O
O
O
Ph
CF3
CF3
Ph
Ph
Ph
H
O
relative
ionization
potential
(kJ/mol)
0
2.6
3.8
20.2
Proof of concept
d)
Pt(+) Pt(-)
undivided cell
Pt(+) Pt(-)
undivided cell
O
O
S
O
S
R1
R2
S
R1 R2
R1
R2
HFIP/AcOH (1:1)
3 V, 6 h
HFIP/AcOH (1:1)
4 V, 8 h
1
2
3
Figure 1. Literature background.
13

Pt(+) Pt(-)
undivided cell
O
O
S
O
S
R1 R2
S
R1 R2
+
R1 R2
HFIP/AcOH (1:1)
3 V, 6 h
1
2
3
Thioanisole derivatives
O
O
S
O
Br
O
S
S
Cl
S
I
F
2c
, 94%, >99:1
2b
, 88%, >99:1
2a
2d
, 90%, >99:1
, 93%, >99:1
O
O
S
O
S
O
S
S
O
Ph
AcO
2gb
H
2h
, 85%, >99:1
2e
, 89%, >99:1
, 84%, >99:1
2f
, 92%, >99:1
O
S
O
S
O
S
O
S
O
AcHN
F3CO
2jb
2lbd
2i
, 50%, >99:1
, 92%, >99:1
2kf
, 30%, >99:1
, 84%, >99:1
CN
O
S
O
S
O
S
EtO
O
2nb
O
2m
2of
, 78%, >99:1
, 86%, >99:1
, 88%, >99:1
Diaryl sulfides
O
S
O
S
O
S
MeO
Me
MeO
Cl
2pf
2qf
, 62%, >99:1
O
2rf
, 75%, >99:1
, 72%, >99:1
O
S
N
S
O
O
2tc
2sf
, 68%, >99:1
Functional sulfides derivatives
, 72%, >99:1
O
S
O
S
O
S
O
O
S
O
Ph
O
Ph
Cl
OEt
Ph
2wb
2u
2v
Cl
, 51%, >99:1
, 60%, >99:1
, 75%, >99:1
2xb
, 70%, >99:1
O
S
O
S
O
S
Ph
Cl
2aa
, 80%, >99:1
2z
, 90%, >99:1
2y
, 87%, >99:1
Dialkyl sulfides and sulfides containing nature product skeleton
O
S
O
S
S
N
O
O
Ts
O
, 90%, >99:1 2acf
2ab
, 79%, >99:1
2adbf
, 68%, >99:1
O
Chemoselectivity
O
S
NO2
O
S
Ph
O
S
Ph
S
2aebf
2afef
, 51%, >99:1
, 80%, >99:1
Figure 2. Scope for the synthesis of sulfoxides 2.a
a
Condition: Pt anode and cathode (15 mm x10 mm x 0.2 mm), undivided cell, voltage = 3 V. Sulfide 1 (0.3
mmol), LiClO4 (0.36 mmol), HOAc (1 mL), HFIP (1 mL), rt, open-air, 6 h. 2a/3a ratio was determined by GC-MS
or LC-MS. 4 V was used. 2.5 V was used. 4 h was used. 3.8 V and HFIP/MeCN(1 mL/1 mL). 0.2 mmol
scale.
b
c
d
e
f
14

Pt(+) Pt(-)
undivided cell
O
O
S
R1
R2
S
R1
R2
HFIP/HOAC (1:1)
4 V, 8 h
1
3
Sulfides
O
O
O
O
O
Br
O
O
O
S
S
Cl
S
S
F
I
3c
, 90%
3b
, 89%
O
3d
, 89%
3a
, 91%
O
O
O
O
O
O
S
O
S
S
S
Ph
Ph
F3CO
3h
, 85%
3g
, 95%
3e
, 94%
3f
, 92%
O
O
S
O
O
S
O
O
O
3i
R = -CN,
, 91%
S
Ph
3n
Ph
3j b
R = -NO2,
, 43%
3k b
S
, 62%
R = -COCH3
, 60%
O
O
3le
3me
, 89%
R
,74%
CN
O
O
S
OEt
O
O
S
S
OBz
O
O
O
O
3r
, 41%
3q
, 89%
3p d
,
58%
Disulfides
OMe
O
O
O
O
O
O
O
S
S
S
OMe
S
MeO
S
S
O
3s c
3t e
3ue
, 71%
,
80%
MeO
,
50%
Figure 3. Scope for the synthesis of sulfones 3.a
a Conditions: Pt anode and cathode (15 mm x10 mm x 0.2 mm), undivided cell, voltage = 4 V. Sulfide 1 (0.3 mmol),
LiClO4 (0.6 mmol), HOAc (1 mL), HFIP (1 mL), rt, open-air, 8 h. b 5 V was used. c 3 V was used. d 2.5 V was used. e
0.2 mmol scale.
Pt(+) Pt(-)
undivided cell
SH
Ar-S-S-R
Ar
S
SH
+
R
HFIP/HOAC (1:1)
3 V, 12 h
6
5
4
S
S
S
S
S
O2N
N
O2N
O2N
6c
, 68%
6a
, 78%
6b
, 82%
S
S
OMe
S
S
S
S
OH
O
O2N
O2N
6e
, 72%
6d
, 65%
6f
, 75%
O
S
S
S
S
OH
S
OAc
S
OMe
Cl
Cl
O
6i
, 50%
6g
6h
, 69%
, 72%
Figure 4. Scope for the synthesis of unsymmetrical disulfides.a
a Conditions: Pt anode and cathode (15 mm x10 mm x 0.2 mm), undivided cell, constant voltage (3 V). Aromatic thiol 4 (0.3
mmol), aliphatic thiol 5 (0.36 mmol), LiClO4 (0.6 mmol), HOAc (1 mL), HFIP (1 mL), rt, open air, 12 h.
15

Br
O
S
Pt(+) Pt(-)
LiClO4 (1.2 equiv)
Br
S
(a)
HFIP/AcOH (1:1)
3 v, 6 h
Argon protection
2a
, 91%
1a
Br
O
S
Pt(+) Pt(-)
LiClO4 (1.2 equiv)
(b)
(c)
TEMPO (1.0 equiv)
+
1a
HFIP/AcOH (1:1)
3 v, 6 h
2a
, 90%
O18
S
O16
S
Pt(+) Pt(-)
S
LiClO4 (1.2 equiv)
+ H2O18
+
HFIP/AcOH (1:1)
3 v, 6 h
, 85%, O16:O18 = 47:53
2f
1f
O16
S
O16
O16
S
O18
O18
S
O18
Pt(+) Pt(-)
LiClO4 (2 equiv)
1f + H2O18
+
+
(d)
(e)
HFIP/AcOH (1:1)
4 v, 5 h
(10 equiv)
3f-1
89% (
3f-2
3f-3
= 1:2.1:1)
3f-1 3f-2 3f-3
:
:
O16
S
O16
+
O16
S
additional
LiClO4 (0.8 equiv)
O18
2)
1)
Pt(+) Pt(-)
LiClO4 (1.2 equiv)
1f
H2O18 (10 equiv)
4 v, 4 h
HFIP/AcOH (1:1)
3 v, 5 h
3f-2
= 7:3)
3f-1
3f-1 3f-2
88% (
:
Figure 5. Investigations of reaction pathways.
(A)
a-LiClO4
200
b
c
b-1a
c-2a
in MeCN
150
100
50
0
a
0.5 1.0 1.5 2.0 2.5
Voltage vs Ag wire / V
(B)
a-LiClO4
150
100
50
b
c
b-1a
c-2a
in HFIP/HOAc=1:1
a
0
0.5 1.0 1.5 2.0 2.5
Voltage vs Ag wire / V
Figure 6. Cyclic voltammetry at a 3 mm diameter Pt electrode.
(A) (a) MeCN solution containing 0.1 M LiClO4 as the supporting electrolyte; (b) MeCN solution containing 0.1 M
LiClO4 and 10 mM 1a; (c) MeCN solution containing 0.1 M LiClO4 and 10 mM 2a. (B) (a) solution of HFIP/HOAc (1:1)
containing 0.1 M LiClO4 as the supporting electrolyte; (b) solution of HFIP/HOAc (1:1) containing 0.1 M LiClO4 and
10 mM 1a; (c) solution of HFIP/HOAc (1:1) containing 0.1 M LiClO4 and 10 mM 2a. Silver wire and Pt wire were used
as the quasi-reference and counter electrode.
16

O
S
O
S
O
S
HOAC / HFIP
(30 mL/10 mL)
HOAC / HFIP
(30 mL/10 mL)
(eq 1)
2eq LiClO4
4v, 50 h
1.2eq LiClO4
3 v, 30 h
1f
2f
(1.43 g, 93%)
3f
(1.61 g, 95%)
1.38 g
(10 mmol)
Figure 7. Gram scale synthesis.
Table 1. Optimization of reaction conditions.a
Pt
Pt
Pt(+) Pt(-)
Br
O
O
Br
O
S
Br
S
S
+
undivided cell
Solvent
Additive
1a
2a
3a
No.
Additive
Volt
Time
6h
6h
6h
6h
6h
6h
6h
6h
8h
8h
8h
8h
6h
Solvent
MeCN
DMF
Yields/% (2a:3a) [b]
1
2
3
4
5
6
7
8
9
LiClO4 (1.2 equiv)
LiClO4 (1.2 equiv)
LiClO4 (1.2 equiv)
LiClO4 (1.2 equiv)
LiClO4 (1.2 equiv)
LiClO4 (1.2 equiv)
LiClO4 (1.2 equiv)
LiClO4 (1.2 equiv)
3V
3V
5 (100:0)
0
3V
3V
3V
3V
HFIP
0
AcOH
MeOH
H2O
41 (100:0)
40 (100:0)
10 (100:0)
98 (>99:1)
32 (97:3)
8 (12:88)
0
3V
HFIP/AcOH = 1/1
HFIP/MeOH = 1/1
HFIP/AcOH = 1/1
AcOH
3V
nBu4NBF4 (2 equiv) 4V
nBu4NBF4 (2 equiv) 4V
nBu4NPF6 (2 equiv) 4V
10
11
12
13c
HFIP/ AcOH =1/1
HFIP/AcOH=1/1
HFIP/ AcOH = 1/1
72 (28:72)
98 (0:100)
0
LiClO4 (2 equiv)
4V
LiClO4 (1.2 equiv)
-
[a] Conditions: Pt anode and cathode (15 mm × 10mm × 0.2mm), constant voltage. 1a (0.3 mmol), additive, solvent
(2.0 mL), room temperature, open-air, 8 h. [b] Determined by GC-MS analysis. c No applied potential.
17

Supplementary information. Details of the general procedure for electrochemical
oxidation of sulfides, mechanistic studies, data of products and copies of NMR
spectra.
1. Modulation of oxidation potential by hydrogen bonding network
2. Chemo-selective oxidation of thioethers to sulfoxides and sulfones
3. Electro-oxidative synthesis of unsymmetrical disulfides
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:
18