Flow Electrosynthesis of Sulfoxides, Sulfones, and Sulfoximines without Supporting Electrolytes

Article abstract of DOI:10.1021/acs.joc.1c00860

An efficient electrochemical flow process for the selective oxidation of sulfides to sulfoxides and sulfones and of sulfoxides toN-cyanosulfoximines has been developed. In total, 69 examples of sulfoxides, sulfones, andN-cyanosulfoximines have been synthesized in good to excellent yields and with high current efficiencies. The synthesis was assisted and facilitated through a supporting electrolyte-free, fully automated electrochemical protocol that highlights the advantages of flow electrolysis.

Full text of DOI:10.1021/acs.joc.1c00860

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Article
Flow Electrosynthesis of Sulfoxides, Sulfones, and Sulfoximines
without Supporting Electrolytes
Nasser Amri and Thomas Wirth*
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Supporting Information
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ABSTRACT: An efficient electrochemical flow process for the
selective oxidation of sulfides to sulfoxides and sulfones and of
sulfoxides to N-cyanosulfoximines has been developed. In total, 69
examples of sulfoxides, sulfones, and N-cyanosulfoximines have
been synthesized in good to excellent yields and with high current
efficiencies. The synthesis was assisted and facilitated through a
supporting electrolyte-free, fully automated electrochemical proto-
col that highlights the advantages of flow electrolysis.
INTRODUCTION
■
Since ancient times, organosulfur compounds have attracted
the attention of chemists because of their importance in
medicine and pharmaceutical products.1,2 Many biologically
active compounds and natural products contain sulfoximine,
sulfoxide, or sulfone functional groups. Notably, sulfoximine,
sulfoxide, or sulfone functional groups are very important in
antibiotic, musculoskeletal, metabolism, alimentary tract, or
anti-inflammatory drugs (Figure 1).3−5
Additionally, there is an exceptionally rich chemistry of
organosulfur compounds in organic synthesis. The oxygen of
the sulfinyl group has the ability to coordinate with different
carbon ligands and metal ions, in addition to the stereo-
electronic effects and the conformational stability that exists in
the sulfinyl group. Sulfoximines and sulfoxides are stable
functional groups that have been used as ligands as
enantiopure compounds also in asymmetric synthesis.6−9
Many variations of the organosulfur oxidation process have
been developed to generate more viable and long-lasting
oxidative procedures that will have an impact on the
pharmaceutical industry to reduce cost, waste, and byproducts.
Generally, such oxidation processes can be performed using
different oxidants such as peroxides,10,11 photocatalytic
processes,8,12 or hypervalent iodine reagents.13−15 Continuous
processes have been investigated as well.16 Despite these
developments in organosulfur oxidation processes, most lack
industrial interest, owing to sustainability, scaling-up, and
safety concerns.
Figure 1. Examples of biological relevant sulfoxide, sulfone, and
sulfoximine compounds.
Recently, a resurgence of organic electrosynthesis has been
observed in the context of modern synthesis.17−21 As a
sustainable tool, electrons can be used to perform oxidation
and reduction processes in clean and often environmentally
benign procedures by replacing chemical oxidants and
reductants with inexpensive electricity.22,23 Anodic oxidation
of sulfur has been applied in the successful synthesis of
organosulfur compounds through controlled potential elec-
Special Issue: Electrochemistry in Synthetic Organic
Chemistry
Received: April 14, 2021
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© XXXX American Chemical Society
A

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a
̈
trolysis. Noel and co-workers have reported the direct
Table 1. Conversion of 1a to 2a and 3a
oxidation of thioethers to the corresponding sulfoxides or
sulfones in the presence of supporting electrolytes under flow
reaction conditions.24 Yudin et al. reported a method for the
amination of sulfoxides in batch electrolysis using a divided
cell.25 Potentiostatic anodic oxidation conditions have been
applied in these reactions. Generally, using a divided cell leads
to increased cell potentials.26
There has been significant growth in the field of electro-
organic synthesis over the past few years. Electroorganic
synthesis in a flow reactor is a highly useful tool to perform
redox transformations in a more proficient manner, while
overcoming some of the constraints such as low reaction rates,
large current gradients, and low conductivity of organic
solvents in batch electrolysis. In addition, there have been
innovations in flow cells that have permitted selective and
successful synthesis, exploiting the usually high electrode
surface-to-reactor volume ratio, which, in turn, translates to a
higher mass transfer and higher productivity.27−30
current
[mA]
conversion
2a
3a
b
b
b
entry
anode
Pt
Pt
Pt
cathode
Pt
[%]
[%]
[%]
1
2
3
4
5
6
7
8
64 (2F)
Pt on Ti 64 (2F)
90
95
98
90
96
98
98
98
48
100
98
98
98
83
92
86
90
96
98
98
98
48
27
40
11
12
7
3
12
0
0
0
0
0
0
73
58
87
87
Gr
64 (2F)
64 (2F)
64 (2F)
64 (2F)
64 (2F)
64 (2F)
64 (2F)
128 (4F)
128 (4F)
160 (5F)
192 (6F)
Pt on Ti Pt
Gr
Gr
Gr
GC
Fe
Gr
Pt
Gr
Pt
Fe
Pt
Fe
Fe
Fe
Fe
Fe
9
10
11
12
13
Pt
Pt
RESULTS AND DISCUSSION
■
In an extension of our previous efforts toward the development
of flow tools and techniques to implement flow trans-
formations,31,32 we recently have reported a reaction without
using a supporting electrolyte33 and disclosed the first use of an
integrated flow electrochemical reactor in an automated
way.34,35 We saw this as an opportunity to further improve
and simplify the oxidation methodologies of organosulfur
compounds.36
a
Conditions: [1a] = 0.1 M, MeCN/H2O (9:1), flow rate = 0.2 mL
b
min−1, at room temperature, reactor volume = 0.6 mL. Determined
by 1H NMR spectroscopy with 1,3,5-trimethoxybenzene as an internal
standard.
detected (see the Supporting Information). An increase in the
charge from 2 to 4 F led to the formation of sulfone in 73%
yield. Replacing the Gr by a Pt electrode and applying 5 F led
to significant yields of sulfone (Table 1, entry 12). Passing
more charge did not improve the yield further (Table 1, entry
13). The optimal reaction conditions for sulfoxide and sulfone
formation are shown in entry 7 and entry 12 in Table 1,
respectively.
With the optimized reaction conditions in hand, the
influence of the applied current on the observed high
selectivity was explored in the synthesis of sulfoxides and
sulfones derivatives as shown in Scheme 1. Aryl thioethers with
electron-donating and electron-withdrawing substituents of-
fered sulfoxides or sulfones in good to excellent yields.
Thioanisol (1a) provided sulfoxide and sulfone in excellent
yield of 87% and 81%, respectively. Thioanisol derivatives 1b−
o reacted efficiently to afford the desired sulfoxides 2b−o and
sulfones 3b−o in 15−90% yield. Functional groups, such as
fluoro-, chloro-, bromo- and aldehyde substitutions were well
tolerated. Also, 3,5-dichlorothioanisol 1p delivered the desired
products 2p and 3p in reasonable yields.
Furthermore, sulfides containing different alkyl and aryl
groups such as ethyl, propyl, cyclopropyl, allyl, benzyl, and
phenyl 1q−1v were oxidized under optimized conditions,
giving moderate to good, isolated yields. Sulfide 1w bearing a
ketone also offered sulfoxide 2w and sulfone 3w products. Of
note is that benzyl-substituted 1u did not form the desired
sulfone.
Heterocyclic thioether 1x was also amenable to the reaction
conditions. Moreover, these two methods were successfully
applied to oxidize dibutyl sulfide 1y and cyclic sulfide 1z and
heterocyclic sulfide containing one oxygen atom 1aa to offer
the corresponding sulfoxide and sulfone products. In these
reactions, a catalytic amount of supporting electrolyte
Bu4NBF4 was added to increase the cell conductivity and
decrease the high cell voltage. For sulfoxides 2 using method A
In this work, we report a green synthesis method of
sulfoxides, sulfones, and sulfoximines without any additional
supporting electrolytes through a controlled current using an
electrochemical flow reactor attached to a fully automated
system. Unique features of the Vapourtec automatic flow
system with an integrated electrochemical ion microflow
reactor speed up the reaction, while largely reducing the
amount of manpower needed to execute the reactions. The
device self-loads chemicals, collects reaction products, and
autocleans the system, while allowing for specific reaction
temperatures, flow rates, and current control for each reaction.
Initially, the reaction of thioanisol (1a) in a mixture of
acetonitrile/water (9:1) was examined using different reaction
conditions, electrode materials, and electrical current. The
reaction proceeds in the absence of any additional supporting
electrolyte due to the close distance of the electrodes in the
flow reactor (0.5 mm).33,37 In this reaction, different electrodes
such as graphite (Gr), platinum (Pt), platinum coated on Ti,
glassy carbon (GC), and stainless steel (Fe) were screened,
and among these, Gr as an anode and stainless steel as a
cathode showed the highest selectivity toward sulfoxide
formation in 98% yield (Table 1, entries 1−10). The formation
of sulfone as an over oxidized product in 3−12% yield was
observed with Pt as an anode material (Table 1, entries 1−3).
Gr and GC anodes gave similar yields, and Gr was selected as
the most cost-efficient electrode material (Table 1, entries 6−
8). To reduce the reaction time, the flow rate was increased
from 0.1 mL min−1 to 0.3 mL min−1. At 0.2 mL min−1, still
98% yield was obtained, but at higher flow rates, lower yields
were observed (see Supporting Information). Replacing
acetonitrile with methanol or water with hexafluoro-2-propanol
(HFIP) resulted in decreased yields (see Supporting
Information). An increase in the sulfide concentration led to
reduced yields of the product, and traces of sulfone were
B
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a
Scheme 1. Substrate Scope for the Electrochemical
Oxidation of Sulfides
Table 2. Reaction to 5a
a
b
entry
anode
cathode
solvent
conversion [%]
1
2
3
4
5
6
7
8
C
C, Pt, or Fe
C
HFIP
HFIP
HFIP
MeCN
MeOH
TFE
0
8
25
18
4
6
0
34
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
c
HFIP
HFIP
d
a
Conditions: [2a] = 0.05 M, [4] 0.075 M, flow rate = 0.1 mL min−1, I
= 24 mA (3 F), supporting electrolyte = Et4NCl (0.01 M), reactor
b
volume = 0.3 mL. Determined by 1H NMR spectroscopy.
c
d
Supporting electrolyte: Et4NI, Et4NBr, or n-Bu4NBr. Without
supporting electrolyte.
such as acetonitrile, methanol, and trifluoroethanol (TFE) led
to lower product yields (Table 2, entry 4−6). No product was
formed when different supporting electrolytes were examined
(Table 2, entry 7). Interestingly, the highest yield was observed
in the absence of any supporting electrolyte (Table 2, entry 8),
although, for all of these experiments, a thinner spacer (0.25
mm thickness) was used to reduce the high voltage observed in
the reactions.
Initial screening showed that the platinum electrodes and
hexafluoro-2-propanol (HFIP) were the appropriate materials
for this reaction. It is known that HFIP has the ability to
stabilize radicals in electrochemical reactions.38 To study the
effect of the reaction time, the flow rate was screened from
0.075 mL min−1 to 0.2 mL min−1, and an improvement in yield
was observed with a flow rate of 0.15 mL min−1 (Table 3, entry
a
Table 3. Reactions Conditions for the Synthesis of 5a
b
entry
flow rate (mL min−1
)
I (mA)
F
conversion [%]
a
Method A: [1] = 0.1 M, MeCN/H2O (9:1), Gr (+)/Pt(−), 64 mA,
1
2
3
4
5
6
7
8
0.075
0.1
0.15
0.2
0.15
0.15
0.15
0.15
18
24
36
48
48
72
36
144
3
33
34
40
17
48
68
43
62
flow rate = 0.2 mL min−1, reactor volume = 0.6 mL, rt. Method B: [1]
= 0.1 M, MeCN/H2O (9:1), Pt(+)/Fe(−), 160 mA, flow rate = 0.2
3
3
3
4
b
mL min−1, reactor volume = 0.6 mL, rt. 0.01 M of Bu4NBF4 was
used.
6
c
6
6
and sulfones 3 using method B, high selectivities were
observed in all cases.
d
a
This method was then extended to the synthesis of
sulfoximines 5. However, a simple addition of cyanamide 4
to the electrolysis solution led only to the formation of the
corresponding sulfoxides. Therefore, sulfoxide 2a prepared in
the previous reaction was examined as a starting material
together with cyanamide 4 under different reaction conditions
for the formation of 5a.
Initially, a Gr anode and different cathodes materials such as
Gr, Pt, and Fe were investigated, but the reaction did not occur
(Table 2, entry 1). The use of a platinum anode and graphite
cathode led only to a low yield of 8% (Table 2, entry 2), while
the yield increased when platinum was used as an anode and
cathode (Table 2, entry 3). Hexafluoro-2-propanol (HFIP)
was determined to be the solvent of choice, and other solvents
Conditions: [2a] = 0.05 M, [4] 0.075 M, reactor volume = 0.3 mL.
b
c
d
Determined by 1H NMR spectroscopy. [2a] = 0.025 M. [2a] = 0.1
M.
3). Then, increasing the electrical charge from 3 to 6 F led to a
further increase in the yield to 68% (Table 3, entries 5 and 6).
A decrease or increase in the sulfoxide concentration (0.025 or
0.1 M) led to reduced yields of the product (Table 3, entries 7
and 8).
With the optimized conditions in hand, different sulfoxides
obtained from the previous method were evaluated. Both
electron-donating and electron-withdrawing substituents in the
para- and meta-positions of alkyl aryl sulfoxides delivered good
yields of the corresponding N-cyanosulfoximines 5a−i. No
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reaction occurred with ortho-substituted sulfoxides 5j−k,
probably because of steric reasons. Replacing the S-methyl
group to other alkyl groups resulted in a corresponding
sulfoximine where S-ethyl-S-phenylsulfoximine 5m, S-propyl-S-
phenylsulfoximine 5n, and S-cyclopropyl-S-phenylsulfoximine
5o were obtained in 43%, 40%, and 38% yields, respectively.
However, diaryl sulfoxide provided only a low yield of 5p.
Notably, S-methyl-S-pyridinylsulfoximine 5q and cyclic sulfox-
imines 5r were also obtained in moderate yields as shown in
Scheme 2. Finally, the protected N-cyanosulfoximines were
converted into NH-sulfoximines 6 by treatment with trifluoro-
acetic anhydride (TFAA), followed by the addition of
K2CO3.39
A combination of both oxidation sequences from sulfides to
N-cyanosulfoximines as the final product in one flow setup was
investigated. For this purpose, two electrochemical flow
reactors were connected with a packed bed column of
MgSO4 inbetween, which allowed an in-line removal of
water. As shown in Scheme 3, the thioanisol 1a in HFIP/
H2O was injected to the first reactor to form sulfoxide 2a,
followed by the packed bed filled with MgSO4 to remove the
remaining water. The cyanamide 4 in HFIP was added before
the second reactor to deliver the N-cyanosulfoximine 5a as a
final product in 26% yield overall. The use of HFIP as a solvent
in place of MeCN in the first step had an adverse impact on
the sulfoxide formation.
To further explore the reaction mechanism, the oxidation of
1a was carried out in the absence of water with the addition of
Bu4NBF4 as a supporting electrolyte, no sulfoxide product was
observed, and only the starting material was detected. Also, we
conducted the oxidation of thioanisol 1a in the presence of
H218O under the same reaction conditions. The sulfoxide
product contained 18O labeling, which was confirmed by
HRMS analysis. This result proves that the oxygen atom stems
from water and any dissolved O2 did not play a role in this
reaction.
Scheme 2. Substrate Scope for the Electrochemical
a
Formation of N-Cyanosulfoximines
Additionally, cyclic voltammetry studies of the sulfide and
sulfoxide in acetonitrile were conducted to obtain insight into
the reaction mechanism in various solutions. Two one-electron
oxidation peaks of thioanisol 1a were observed in acetonitrile
at Ep = 1.57 V and Ep = 1.9 V (Figure 2a, yellow line), while
there was only one apparent oxidation peak for sulfoxide 2a at
Ep = 2.05 V (Figure 2a, blue line). Also, the cyclic voltammetry
of sulfoxide 2a in HFIP showed one oxidation peak at Ep = 2.1
V (Figure 2b, orange line), while there was no oxidation peak
for cyanamide 4 (Figure 2b, gray line).
Based on our initial studies and according to previous
literature reports on the oxygenation of sulfides,40−42 the
proposed mechanism for the oxygenation and amination of
sulfides/sulfoxides is shown in Scheme 4. In the initial step,
sulfide 1 is oxidized at the anode to produce sulfide radical
cation intermediate I, while water is reduced at the cathode to
generate the hydroxide ions (OH−), which then react with I to
generate the sulfoxide 2. Subsequently, sulfoxide 2 undergoes a
second single electron transfer (SET), generating sulfoxide
radical cation intermediate II, which reacts with hydroxide ions
(OH−) to produce sulfone 3 or react with cyanamide 4 to
produce N-cyanosulfoximines 5. The proton generated in this
process will be finally reduced to hydrogen at the cathode.
CONCLUSIONS
■
a
Conditions: [2] = 0.05 M, [4] = 0.125 M, HFIP, Pt (+)/Pt (−), 72
In conclusion, an electrochemical flow protocol for the rapid
synthesis of sulfoxides, sulfones, and N-cyanosulfoximines has
been developed. A broad range of sulfoxides (27 examples),
sulfones (26 examples), and N-cyanosulfoximines (16
mA, flow rate = 0.15 mL min−1, reactor volume = 0.3 mL, rt.
Scheme 3. Amination of Sulfide 1a to Sulfoximine 5a in a Combined Flow Setup
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Figure 2. Cyclic voltammetry (CV) studies of thioanisol 1a (yellow line) and sulfoxide 2a (blue line) in MeCN (a). Sulfoxide 2a (orange line) and
cyanamide 4 (gray line) in HFIP (b). GC carbon disk working electrode (immersed surface area = 3 mm2), Pt counter electrode (immersed surface
area = 1.2 mm2), Ag/0.01 M AgCl reference electrode, 20 mV s−1.
Scheme 4. Proposed Mechanism for the Electrochemical Synthesis of Sulfoxides, Sulfones, and Sulfoximines
by an ion electrochemical power supply. The cyclic voltammogram
studies were performed using an Orygalys OGF500 Potentiostat/
Galvanostat with OGFPWR power supply.
examples) was synthesized in good to excellent yields using an
automated electrochemical flow system in the absence of any
supporting electrolyte.
General Procedure for the Electrochemical Oxidation of
Sulfides to Sulfoxides (GP1). The electrolysis was performed in an
undivided cell using a Vapourtec Ion electrochemical flow reactor
(reactor volume = 0.6 mL, spacer 0.5 mm) using a graphite (Gr)
electrode as the anode and a stainless steel (Fe) electrode as the
cathode (active surface area: A = 12 cm2). A solution of sulfide (0.1
M) in a mixture of CH3CN and H2O (9:1) placed in a 20 mL vial
screw cap with a hole with a PTFE/silicone septum. The reaction
mixture was injected to an 18 mL sample loop. After that, the reactor
temperature was set at room temperature with a flow rate of 0.2 mL/
min, and the current was set at 64 mA turn on automatically. Then,
solutions were pumped into the electrochemical reactor. After
reaching a steady state, the solution (15 mL, 1.5 mmol) was collected
automatically into a glass vial. The solvent was removed under a
vacuum. The crude product was purified by column chromatography
(EtOAc/cyclohexane).
General Procedure for the Electrochemical Oxidation of
Sulfides to Sulfones (GP2). The electrolysis was performed in an
undivided cell using a Vapourtec Ion electrochemical flow reactor
(reactor volume = 0.6 mL, spacer 0.5 mm) using a graphite (Pt)
electrode as the anode and a stainless steel (Fe) electrode as the
cathode (active surface area: A = 12 cm2). A solution of sulfide (0.1
M) in a mixture of CH3CN and H2O (9:1) placed in a 20 mL vial
screw cap with a hole with a PTFE/silicone septum. The reaction
mixture was injected to an 18 mL sample loop. After that, the reactor
temperature was set at room temperature with a flow rate of 0.2 mL/
min, and the current was set at 160 mA turn on automatically. Then,
solutions were pumped into the electrochemical rector. After reaching
a steady state, the solution (15 mL, 1.5 mmol) was collected
automatically into a glass vial. The solvent was removed under a
EXPERIMENTAL SECTION
■
All solvents, reagents, thioether substrates 1, and cyanamide 4 were
purchased from Sigma-Aldrich, Acros Organic, Fluorochem, Alfa
Aesar, and TCI chemicals and used as received without purification or
drying. Thin-layer chromatography (TLC) was performed on
precoated aluminum sheets of Merck silica gel 60 F254 (0.20 mm)
and visualized by UV radiation (254 nm). Automated column
chromatography was performed on a Biotage Isolera Four using
Biotage cartridges SNAP Ultra 10 g. H NMR, 13C NMR, and 19F
1
NMR spectra were measured on a Bruker DPX 400 or 500 apparatus
and were referenced to the residual proton solvent peak (1H: CDCl3,
δ 7.26 ppm; DMSO-d6, δ 2.50 ppm) and solvent 13C signal (CDCl3, δ
77.2 ppm, DMSO-d6, δ 39.5). Chemical shifts (δ) were reported in
ppm, and multiplicity of the signals was declared as followed: s =
singlet, d = doublet, t = triplet, q = quartet, quin = quintet, sex =
sextet, hep = septet, dd = doublet of doublets, m = multiplet, b =
broad; coupling constants (J) in were recorded in hertz. IR spectra
were recorded on a Shimadzu FTIR Affinity-1S apparatus. Wave
numbers are quoted in cm−1. All compounds were measured neat
directly on the crystal of the IR machine. Mass spectrometric
measurements were performed by R. Jenkins, R. Hick, T. Williams,
and S. Waller at Cardiff University on a Water LCR Premier XEtof.
Ions were generated by electron ionization (EI) and electron spray
(ES). The molecular ion peaks values quoted for either molecular ion
[M]+, molecular ion plus hydrogen [M + H]+, or molecular ion plus
sodium [M + Na]+. Melting points were measured using a
Gallenkamp variable heater with samples in open capillary tubes.
The electrochemical reactions were carried out in a galvanostatic
mode using a Vapourtec Ion electrochemical flow reactor powered up
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vacuum. The crude product was purified by column chromatography
(EtOAc/cyclohexane).
4-(Methylsulfinyl)benzonitrile (2f). Compound 2f was synthe-
sized following GP1 using (4-(methylthio)benzonitrile (1f, 224 mg,
1.5 mmol) to give the product as a white solid. It was purified by
column chromatography on silica gel using cyclohexane/ethyl acetate
(4:6) to obtain 82% yield (204 mg). Mp: 86−88 °C [lit. 87−89
°C].41 1H NMR (500 MHz, CDCl3) δ 7.96−7.68 (m, 4H), 2.76 (s,
3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 151.6, 133.1, 124.4,
117.8, 114.9, 44.0 ppm. The spectroscopic data agree with the
literature.45
1-Methoxy-4-(methylsulfinyl)benzene (2g). Compound 2g
was synthesized following GP1 using (4-methoxyphenyl)(methyl)-
sulfane (1g, 231 mg, 1.5 mmol) to give the product as a colorless oil.
It was purified by column chromatography on silica gel using ethyl
acetate (100%) to obtain 88% yield (224 mg). Mp: 42−44 °C [lit.
42−44 °C].41 1H NMR (400 MHz, CDCl3) δ 7.63−7.55 (m, 2H),
7.06−6.99 (m, 2H), 3.85 (s, 3H), 2.69 (s, 3H) ppm. 13C{1H} NMR
(101 MHz, CDCl3) δ 162.1, 136.8, 125.6, 114.9, 55.6, 44.1 ppm. The
spectroscopic data agree with the literature.40
4-(Methylsulfinyl)benzaldehyde (2h). Compound 2h was
synthesized following GP1 using 4-(methylthio)benzaldehyde (1h,
228 mg, 1.5 mmol) to give the product as a white solid. It was purified
by column chromatography on silica gel using cyclohexane/ethyl
acetate (4:6) to obtain 68% yield (174 mg). Mp: 83−86 °C [lit. 84−
87 °C].46 1H NMR (500 MHz, CDCl3) δ 10.09 (s, 1H), 8.05 (d, J =
7.7 Hz, 2H), 7.82 (d, J = 7.7 Hz, 2H), 2.78 (s, 3H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 191.1, 152.4, 138.0, 130.3, 124.1, 43.7
ppm. The spectroscopic data agree with the literature.43
General Procedure for the Electrochemical Imination of
Sulfoxides (GP3). The electrolysis was performed in an undivided
cell using a Vapourtec Ion electrochemical flow reactor (reactor
volume = 0.3 mL, spacer 0.25 mm) using a platinum (Pt) electrode as
an anode and cathode (active surface area: A = 12 cm2). A solution of
sulfoxide (0.05 M) and cyanamide (1.5 equiv) in HFIP (12 mL) was
placed in a 20 mL vial screw cap with a hole with a PTFE/silicone
septum. The reaction mixture was injected to the 12 mL sample loop.
After that, the reactor temperature was set at room temperature with a
flow rate of 0.15 mL/min, and the current was set at 72 mA turn on
automatically. Then, solutions were pumped into the electrochemical
rector. After reaching a steady state, the solution (10 mL, 0.5 mmol)
was collected automatically into a glass vial. The solvent was removed
under a vacuum. The crude product was purified by column
chromatography (EtOAc/cyclohexane).
General Procedure for the Reduction of N-Cyanosulfox-
imines (GP4). To a mixture solution of N-cyanosulfoximine (0.5
mmol) in CH2Cl2 (10 mL) at 0 °C was added TFAA (1.5 mmol).
The reaction mixture was allowed to stir at room temperature until
the starting material was consumed (monitored by TLC). The
mixture was quenched with water (10 mL). The aqueous layer was
extracted with CH2Cl2 (3 × 10 mL). The combined organic layers
were dried over anhydrous MgSO4, filtered, and evaporated. The
residue was purified by column chromatography (EtOAc/cyclo-
hexane).
(Methylsulfinyl)benzene (2a). Compound 2a was synthesized
following GP1 using methyl(phenyl)sulfane (1a, 186 mg, 1.5 mmol)
to give the product as a colorless oil. It was purified by column
chromatography on silica gel using ethyl acetate (100%) to obtain
87% yield (183 mg). 1H NMR (500 MHz, CDCl3): δ 7.72−7.63 (m,
2H), 7.57−7.48 (m, 2H), 2.72 (s, 3H) ppm. 13C{1H} NMR (126
MHz, CDCl3): δ 145.7, 131.1, 129.4, 123.6, 44.0 ppm. The
spectroscopic data agree with literature.43
1-(Methylsulfinyl)-4-nitrobenzene (2i). Compound 2i was
synthesized following GP1 using methyl(4-nitrophenyl)sulfane (1i,
254 mg, 1.5 mmol) to give the product as a yellow oil. It was purified
by column chromatography on silica gel using ethyl acetate (100%) to
1
obtain 63% yield (174 mg). H NMR (500 MHz, CDCl3) δ 8.43−
8.34 (m, 2H), 7.88−7.78 (m, 2H), 2.79 (s, 3H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 153.4, 149.6, 124.8, 124.6, 44.0 ppm. The
spectroscopic data agree with the literature.40
1-Methyl-4-(methylsulfinyl)benzene (2b). Compound 2b was
synthesized following GP1 using methyl(p-tolyl)sulfane (1b, 207 mg,
1.5 mmol) to give the product as a colorless oil. It was purified by
column chromatography on silica gel using ethyl acetate (100%) to
obtain 89% yield (207 mg). 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J
= 7.4 Hz, 2H), 7.33 (d, J = 7.6 Hz, 2H), 2.70 (s, 3H), 2.41 (s, 3H)
ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 142.6, 141.7, 130.2, 123.7,
44.1, 21.5 ppm. The spectroscopic data agree with the literature.40
1-Bromo-4-(methylsulfinyl)benzene (2c). Compound 2c was
synthesized following GP1 using (4-bromophenyl)(methyl)sulfane
(1c, 305 mg, 1.5 mmol) to give the product as a white solid. It was
purified by column chromatography on silica gel using ethyl acetate
(100%) to obtain 86% yield (282 mg). Mp: 86−88 °C [lit. 85−87
°C].44 1H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 8.3 Hz, 2H), 7.52
(d, J = 8.3 Hz, 2H), 2.71 (s, 3H) ppm. 13C{1H} NMR (126 MHz,
CDCl3) δ 145.1, 132.8, 125.7, 125.4, 44.2 ppm. The spectroscopic
data agree with the literature.40
1-Methyl-3-(methylsulfinyl)benzene (2j). Compound 2j was
synthesized following GP1 using methyl(m-tolyl)sulfane (1j, 207 mg,
1.5 mmol) to give the product as a yellow oil. It was purified by
column chromatography on silica gel using ethyl acetate (100%) to
1
obtain 86% yield (200 mg). H NMR (500 MHz, CDCl3) δ 7.49−
7.45 (m, 1H), 7.41−7.36 (m, 2H), 7.30−7.26 (m, 1H), 2.70 (s, 3H),
2.41 (s, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 145.6, 139.7,
131.9, 129.2, 123.9, 120.7, 44.0, 21.5 ppm. The spectroscopic data
agree with the literature.40
1-Bromo-3-(methylsulfinyl)benzene (2k). Compound 2k was
synthesized following GP1 using (3-bromophenyl)(methyl)sulfane
(1k, 305 mg, 1.5 mmol) to give the product as a yellow oil. It was
purified by column chromatography on silica gel using ethyl acetate
(100%) to obtain 90% yield (296 mg). 1H NMR (500 MHz, CDCl3)
δ 7.84−7.76 (m, 1H), 7.64−7.50 (m, 2H), 7.42−7.36 (m, 1H), 2.72
(s, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 148.1, 134.2,
130.9, 126.6, 123.7, 122.2, 44.1 ppm. The spectroscopic data agree
with the literature.42
1-Chloro-3-(methylsulfinyl)benzene (2l). Compound 2l was
synthesized following GP1 using (3-chlorophenyl)(methyl)sulfane
(1l, 238 mg, 1.5 mmol) to give the product as a colorless oil. It was
purified by column chromatography on silica gel using ethyl acetate
(100%) to obtain 85% yield (224 mg). 1H NMR (500 MHz, CDCl3)
δ 7.65 (s, 1H), 7.50−7.43 (m, 3H), 2.73 (s, 3H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 148.0, 135.8, 131.3, 130.7, 123.7, 121.7, 44.1
ppm. The spectroscopic data agree with the literature.42
1-Chloro-4-(methylsulfinyl)benzene (2d). Compound 2d was
synthesized following GP1 using (4-chlorophenyl)(methyl)sulfane
(1d, 238 mg, 1.5 mmol) to give the product as a colorless oil. It was
purified by column chromatography on silica gel using ethyl acetate
(100%) to obtain 83% yield (217 mg). 1H NMR (500 MHz, CDCl3)
δ 7.58 (d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 2.71 (s, 3H) ppm.
13C{1H} NMR (126 MHz, CDCl3) δ 144.3, 137.4, 129.8, 125.1, 44.2
ppm. The spectroscopic data agree with the literature.40
1-Fluoro-4-(methylsulfinyl)benzene (2e). Compound 2e was
synthesized following GP1 using (4-fluorophenyl)(methyl)sulfane
(1e, 213 mg, 1.5 mmol) to give the product as a yellow oil. It was
purified by column chromatography on silica gel using ethyl acetate
(100%) to obtain 80% yield (190 mg). 1H NMR (500 MHz, CDCl3)
δ 7.68−7.61 (m, 2H), 7.25−7.16 (m, 2H), 2.70 (s, 3H) ppm.
13C{1H} NMR (126 MHz, CDCl3) δ 164.4 (d, J = 251.4 Hz), 141.2
(d, J = 3.1 Hz), 125.9 (d, J = 8.9 Hz), 116.8 (d, J = 22.6 Hz) ppm. 19F
NMR (471 MHz, CDCl3) δ −152.06 ppm. The spectroscopic data
agree with the literature.40
1-Bromo-2-(methylsulfinyl)benzene (2m). Compound 2m was
synthesized following GP1 using (2-bromophenyl)(methyl)sulfane
(1m, 305 mg, 1.5 mmol) to give the product as a yellow oil. It was
purified by column chromatography on silica gel using cyclohexane/
1
ethyl acetate (4:6) to obtain 72% yield (238 mg). H NMR (500
MHz, CDCl3) δ 7.94 (dd, J = 7.8, 1.7 Hz, 1H), 7.62−7.54 (m, 2H),
7.39−7.35 (m, 1H), 2.82 (s, 3H) ppm. 13C{1H} NMR (126 MHz,
CDCl3) δ 145.5, 133.0, 132.4, 128.8, 125.8, 118.5, 42.0 ppm. The
spectroscopic data agree with the literature.43
F
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1-Chloro-2-(methylsulfinyl)benzene (2n). Compound 2n was
synthesized following GP1 using (2-chlorophenyl)(methyl)sulfane
(1n, 238 mg, 1.5 mmol) to give the product as a yellow oil. It was
purified by column chromatography on silica gel using cyclohexane/
1H NMR (500 MHz, CDCl3) δ 7.51−7.33 (m, 3H), 7.32−7.22 (m,
2H), 6.98 (d, J = 7.2 Hz, 1H), 4.05 (dd, J = 50.0, 12.6 Hz, 1H) ppm.
13C{1H} NMR (126 MHz, CDCl3) δ 142.8, 131.3, 130.5, 129.2,
128.9, 128.5, 128.3, 124.6, 63.7 ppm. The spectroscopic data agree
with the literature.47
1
ethyl acetate (4:6) to obtain 79% yield (208 mg). H NMR (500
MHz, CDCl3) δ 7.94 (dd, J = 7.8, 1.6 Hz, 1H), 7.53 (td, J = 7.5, 1.2
Hz, 1H), 7.44 (td, J = 7.4, 1.5 Hz, 1H), 7.39 (d, J = 1.2 Hz, 1H), 2.81
(s, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 143.7, 132.1,
129.9, 128.3, 125.4, 41.7 ppm. The spectroscopic data agree with the
literature.42
Sulfinyldibenzene (2v). Compound 2v was synthesized follow-
ing GP1 using diphenylsulfane (1v, 279 mg, 1.5 mmol) to give the
product as a white solid. It was purified by column chromatography
on silica gel using cyclohexane/ethyl acetate (6:4) to obtain 70% yield
(212 mg). Mp: 68−70 °C [lit. 69−70 °C].25 1H NMR (500 MHz,
CDCl3) δ 7.69−7.58 (m, 2H), 7.47−7.41 (m, 3H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 145.6, 131.1, 129.3, 124.8 ppm. The
spectroscopic data agree with the literature.40
1-Iodo-2-(methylsulfinyl)benzene (2o). Compound 2o was
synthesized following GP1 using (2-iodophenyl)(methyl)sulfane (1o,
375 mg, 1.5 mmol) to give the product as a yellow oil. It was purified
by column chromatography on silica gel using cyclohexane/ethyl
Thiochroman-4-one 1-oxide (2w). Compound 2w was
synthesized following GP1 using thiochroman-4-one (1w, 246 mg,
1.5 mmol) to give the product as a yellow oil. It was purified by
column chromatography on silica gel using cyclohexane/ethyl acetate
1
acetate (4:6) to obtain 34% yield (136 mg). H NMR (500 MHz,
CDCl3) δ 7.89 (t, J = 6.6 Hz, 1H), 7.82−7.79 (t, J = 6.6 Hz, 1H),.63−
7.56 (m, 1H), 7.24−7.17 (m, 1H), 2.77 (s, 3H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 148.4, 139.4, 132.6, 129.7, 125.9, 91.5, 42.3
ppm. The spectroscopic data agree with the literature.47
1,3-Dichloro-5-(methylsulfinyl)benzene (2p). Compound 2p
was synthesized following GP1 using (3,5-dichlorophenyl)(methyl)-
sulfane (1n, 290 mg, 1.5 mmol) to give the product as a white solid. It
was purified by column chromatography on silica gel using ethyl
acetate (100%) to obtain 89% yield (278 mg). Mp: 71−73 °C [lit.
72−74 °C].25 1H NMR (500 MHz, CDCl3) δ 7.50 (d, J = 1.6 Hz,
2H), 7.46−7.44 (m, 1H), 2.74 (s, 3H) ppm. 13C{1H} NMR (126
MHz, CDCl3) δ 149.5, 136.4, 131.2, 122.0, 44.1 ppm. The
spectroscopic data agree with the literature.42
1
(4:6) to obtain 47% yield (128 mg). H NMR (500 MHz, CDCl3) δ
8.11 (dd, J = 7.8, 1.2 Hz, 1H), 7.83 (dd, J = 7.7, 0.9 Hz, 1H), 7.72 (td,
J = 7.6, 1.3 Hz, 1H), 7.62 (td, J = 7.6, 1.2 Hz, 1H), 3.49−3.39 (m,
3H), 2.90−2.81 (m, 1H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ
192.1, 145.6, 134.7, 132.2, 129.3, 128.9, 128.5, 46.7, 30.4 ppm. The
spectroscopic data agree with the literature.50
2-(Methylsulfinyl)pyridine (2x). Compound 2x was synthesized
following GP1 using 2-(methylthio)pyridine (1x, 188 mg, 1.5 mmol)
to give the product as a colorless oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6) to
1
obtain 73% yield (155 mg). H NMR (500 MHz, CDCl3) δ 8.65−
(Ethylsulfinyl)benzene (2q). Compound 2q was synthesized
following GP1 using ethyl(phenyl)sulfane (1q, 207 mg, 1.5 mmol) to
give the product as a yellow oil. It was purified by column
chromatography on silica gel using ethyl acetate (100%) to obtain
8.54 (m, 1H), 8.00 (dt, J = 7.9, 1.0 Hz, 1H), 7.93 (td, J = 7.7, 1.7 Hz,
1H), 7.36 (ddd, J = 7.4, 4.8, 1.1 Hz, 1H), 2.83 (s, 3H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 166.0, 149.6, 138.3, 124.7, 119.5, 41.4
ppm. The spectroscopic data agree with the literature.42
1
91% yield (210 mg). H NMR (500 MHz, CDCl3) δ 7.63−7.55 (m,
1-(Butylsulfinyl)butane (2y). Compound 2y was synthesized
following GP1 using dibutylsulfane (1y, 219 mg, 1.5 mmol) to give
the product as a colorless oil. It was purified by column
chromatography on silica gel using ethyl acetate (100%) to obtain
2H), 7.53−7.46 (m, 3H), 2.89 (dq, J = 13.3, 7.4 Hz, 1H), 2.76 (dq, J
= 13.3, 7.4 Hz, 1H), 1.18 (t, J = 7.4 Hz, 3H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 143.3, 131.0, 129.2, 124.3, 50.4, 6.0 ppm. The
spectroscopic data agree with the literature.40
1
66% yield (160 mg). H NMR (500 MHz, CDCl3) δ 2.67−2.54 (m,
(Propylsulfinyl)benzene (2r). Compound 2r was synthesized
following GP1 using phenyl(propyl)sulfane (1r, 228 mg, 1.5 mmol)
to give the product as a colorless oil. It was purified by column
chromatography on silica gel using ethyl acetate (100%) to obtain
4H), 1.76−1.62 (m, 4H), 1.51−1.33 (m, 4H), 0.90 (t, J = 7.4 Hz,
6H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 52.1, 24.6, 22.1, 13.7
ppm. The spectroscopic data agree with the literature.40
Tetrahydro-2H-thiopyran 1-oxide (2z). Compound 2z was
synthesized following GP1 using tetrahydro-2H-thiopyran (1z, 153
mg, 1.5 mmol) to give the product as a colorless oil. It was purified by
column chromatography on silica gel using ethyl acetate/methanol
(98:2) to obtain 72% yield (128 mg). 1H NMR (500 MHz, CDCl3) δ
2.88−2.74 (m, 1H), 2.73−2.64 (m, 1H), 2.21−2.09 (m, 1H), 1.64−
1.46 (m, 2H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 48.8, 24.7,
19.0 ppm. The spectroscopic data agree with the literature.51
1,4-Oxathiane 4-oxide (2aa). Compound 2aa was synthesized
following GP1 using 1,4-oxathiane (1aa, 156 mg, 1.5 mmol) to give
the product as a colorless oil. It was purified by column
chromatography on silica gel using ethyl acetate/methanol (98:2)
to obtain 67% yield (120 mg). 1H NMR (500 MHz, CDCl3) δ 4.36−
4.23 (m, 1H), 3.80−3.70 (m, 1H), 2.92−2.78 (m, 1H), 2.73−2.60
(m, 1H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 59.1, 46.2 ppm.
The spectroscopic data agree with the literature.52
(Methylsulfonyl)benzene (3a). Compound 3a was synthesized
following GP2 using methyl(phenyl)sulfane (1a, 186 mg, 1.5 mmol)
to give the product as a white solid. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (6:4) to
obtain 81% yield (189 mg). Mp: 89−91 °C [lit. 91 °C].25 1H NMR
(400 MHz, CDCl3) δ 7.93 (d, J = 8.2 Hz, 2H), 7.68−7.51 (m, 3H),
3.04 (s, 3H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 140.7, 133.7,
129.4, 127.4, 44.8 ppm. The spectroscopic data agree with the
literature.42
1
86% yield (218 mg). H NMR (500 MHz, CDCl3) δ 7.67−7.53 (m,
2H), 7.52−7.41 (m, 3H), 2.81−2.69 (m, 2H), 1.83−1.72 (m, 1H),
1.69−1.59 (m, 1H), 1.02 (t, J = 7.4 Hz, 3H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 144.1, 131.0, 129.3, 124.1, 59.3, 16.0, 13.3 ppm.
The spectroscopic data agree with the literature.48
(Cyclopropylsulfinyl)benzene (2s). Compound 2s was synthe-
sized following GP1 using cyclopropyl(phenyl)sulfane (1s, 225 mg,
1.5 mmol) to give the product as a colorless. It was purified by
column chromatography on silica gel using ethyl acetate (100%) to
1
obtain 84% yield (209 mg). H NMR (500 MHz, CDCl3) δ 7.73−
7.56 (m, 2H), 7.55−7.42 (m, 3H), 2.29−2.17 (m, 1H), 1.28−1.19
(m, 1H), 1.06−0.89 (m, 3H) ppm. 13C{1H} NMR (126 MHz,
CDCl3) δ 144.9, 131.0, 129.2, 124.1, 33.9, 3.5, 2.9 ppm. The
spectroscopic data agree with the literature.42
(Allylsulfinyl)benzene (2t). Compound 2t was synthesized
following GP1 using allyl(phenyl)sulfane (1t, 225 mg, 1.5 mmol) to
give the product as a colorless oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6) to
1
obtain 67% yield (166 mg). H NMR (500 MHz, CDCl3) δ 7.64−
7.55 (m, 2H), 7.55−7.46 (m, 3H), 5.78−5.52 (m, 1H), 5.37−5.30
(m, 1H), 5.19 (dq, J = 17.0, 1.2 Hz, 1H), 3.54 (ddd, J = 32.0, 12.7, 7.5
Hz, 2H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 143.0, 131.2,
129.2, 125.4, 124.4, 124.0, 61.0 ppm. The spectroscopic data agree
with the literature.49
(Benzylsulfinyl)benzene (2u). Compound 2u was synthesized
following GP1 using allyl(phenyl)sulfane (1u, 300 mg, 1.5 mmol to
give the product as a white solid. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6) to
obtain 78% yield (254 mg). Mp: 120−122 °C [lit. 122−123 °C].42
1-Methyl-4-(methylsulfonyl)benzene (3b). Compound 3b was
synthesized following GP2 using methyl(p-tolyl)sulfane (1b, 207 mg,
1.5 mmol) to give the product as a white solid. It was purified by
column chromatography on silica gel using cyclohexane/ethyl acetate
(6:4) to obtain 83% yield (212 mg). Mp: 86−87 °C [lit. 87−88
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°C].53 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2H), 7.32
(d, J = 7.3 Hz, 2H), 2.99 (s, 3H), 2.40 (s, 3H) ppm. 13C{1H} NMR
(101 MHz, CDCl3) δ 144.7, 137.7, 123.0, 127.3, 44.6, 21.6 ppm. The
spectroscopic data agree with the literature.49
1-Bromo-4-(methylsulfonyl)benzene (3c). Compound 3c was
synthesized following GP2 using (4-bromophenyl)(methyl)sulfane
(1c, 305 mg, 1.5 mmol) to give the product as a white solid. It was
purified by column chromatography on silica gel using cyclohexane/
ethyl acetate (6:4) to obtain 79% yield (280 mg). Mp: 100−102 °C
[lit. 100−102 °C].42 1H NMR (400 MHz, CDCl3) δ 7.85−7.77 (m,
2H), 7.73−7.66 (m, 2H), 3.04 (s, 3H) ppm. 13C{1H} NMR (101
MHz, CDCl3) δ 139.7, 132.8, 129.1, 44.6 ppm. The spectroscopic
data agree with the literature.42
1-Chloro-4-(methylsulfonyl)benzene (3d). Compound 3d was
synthesized following GP2 using (4-chlorophenyl)(methyl)sulfane
(1d, 238 mg, 1.5 mmol) to give the product as a white solid. It was
purified by column chromatography on silica gel using cyclohexane/
ethyl acetate (6:4) to obtain 73 yield (210 mg). Mp: 92−94 °C [lit.
94−95 °C].42 1H NMR (400 MHz, CDCl3) δ 7.91−7.84 (m, 2H),
7.57−7.51 (m, 2H), 3.08−3.01 (m, 3H) ppm. 13C{1H} NMR (101
MHz, CDCl3) δ 140.6, 139.2, 129.8, 129.0, 44.6 ppm. The
spectroscopic data agree with the literature.42
column chromatography on silica gel using cyclohexane/ethyl acetate
(6:4) to obtain 78% yield (198 mg). H NMR (500 MHz, CDCl3) δ
7.79−7.63 (m, 2H), 7.49−7.40 (m, 2H), 3.03 (s, 3H), 2.43 (s, 3H)
ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 140.5, 139.8, 134.5, 129.3,
127.7, 124.5, 44.6, 21.4 ppm. The spectroscopic data agree with the
literature.57
1
1-Bromo-3-(methylsulfonyl)benzene (3k). Compound 3k was
synthesized following GP2 using (3-bromophenyl)(methyl)sulfane
(1k, 305 mg, 1.5 mmol) to give the product as a white solid. It was
purified by column chromatography on silica gel using cyclohexane/
ethyl acetate (6:4) to obtain 71% yield (252 mg). Mp: 102−103 °C.
1H NMR (500 MHz, CDCl3) δ 8.10−8.05 (m, 1H), 7.89−7.85 (m,
1H), 7.79−7.76 (m, 1H), 7.49−7.42 (m, 1H), 3.06 (s, 3H) ppm.
13C{1H} NMR (101 MHz, CDCl3) δ 142.5, 136.9, 131.1, 130.5,
125.9, 123.4, 44.6. The spectroscopic data agree with the literature.58
1-Chloro-3-(methylsulfonyl)benzene (3l). Compound 3l was
synthesized following GP2 using (3-chlorophenyl)(methyl)sulfane
(1l, 283 mg, 1.5 mmol) to give the product as a white solid. It was
purified by column chromatography on silica gel using e cyclohexane/
ethyl acetate (6:4) to obtain 74% yield (212 mg). Mp: 55−56 °C [lit.
56−58 °C].42 1H NMR (500 MHz, CDCl3) δ 7.93 (t, J = 1.9 Hz,
1H), 7.85−7.81 (m, 1H), 7.64−7.60 (m, 1H), 7.52 (t, J = 7.9 Hz,
1H), 3.06 (s, 3H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 142.3,
135.7, 134.0, 130.9, 127.7, 125.6, 44.5 ppm. The spectroscopic data
agree with the literature.42
1-Fluoro-4-(methylsulfonyl)benzene (3e). Compound 3e was
synthesized following GP2 using (4-fluorophenyl)(methyl)sulfane
(1e, 213 mg, 1.5 mmol) to give the product as a colorless oil. It was
purified by column chromatography on silica gel using cyclohexane/
1-Bromo-2-(methylsulfonyl)benzene (3m). Compound 3m
was synthesized following GP2 using (2-bromophenyl)(methyl)-
sulfane (1m, 305 mg, 1.5 mmol) to give the product as a yellow oil. It
was purified by column chromatography on silica gel using
1
ethyl acetate (6:4) to obtain 66% yield (172 mg). H NMR (500
MHz, CDCl3) δ 7.98−7.90 (m, 2H), 7.26−7.20 (m, 2H), 3.04 (s,
3H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 165.8 (d, J = 256.1
Hz), 136.8 (d, J = 3.2 Hz), 130.4 (d, J = 9.6 Hz), 116.7 (d, J = 22.7
Hz), 44.7 (s) ppm. 19F{1H} NMR (471 MHz, CDCl3) δ − 103.59
ppm. The spectroscopic data agree with the literature.42
4-(Methylsulfonyl)benzonitrile (3f). Compound 3f was synthe-
sized following GP1 using (4-(methylthio)benzonitrile (1f, 224 mg,
1.5 mmol) to give the product as a white solid. It was purified by
column chromatography on silica gel using cyclohexane/ethyl acetate
(2:8) to obtain 68% yield (68 mg). Mp: 142−143 °C [lit. 142−143
°C].54 1H NMR (500 MHz, CDCl3) δ 8.11−8.03 (m, 2H), 7.91−7.84
(m, 2H), 3.08 (s, 3H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ
144.6, 133.3, 128.3, 117.7, 117.1, 44.3 ppm. The spectroscopic data
agree with the literature.49
1-Methoxy-4-(methylsulfonyl)benzene (3g). Compound 3g
was synthesized following GP2 using (4-methoxyphenyl)(methyl)-
sulfane (1g, 231 mg, 1.5 mmol) to give the product as a white solid. It
was purified by column chromatography on silica gel using
cyclohexane/ethyl acetate (6:4) to obtain 78% yield (218 mg). Mp:
118−120 °C [lit. 120−122 °C].42 1H NMR (400 MHz, CDCl3) δ
7.93−7.72 (m, 2H), 7.10−6.90 (m, 2H), 3.86 (s, 3H), 3.01 (s, 3H)
ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 163.8, 132.4, 129.6, 114.6,
55.8, 44.9 ppm. The spectroscopic data agree with the literature.42
4-(Methylsulfonyl)benzaldehyde (3h). Compound 3h was
synthesized following GP2 using 4-(methylthio)benzaldehyde (1h,
228 mg, 1.5 mmol) to give the product as a white solid. It was purified
by column chromatography on silica gel using cyclohexane/ethyl
acetate (6:4) to obtain 35% yield (96 mg). Mp: 157−158 °C [lit.
157−158 °C].55 1H NMR (400 MHz, CDCl3) δ 10.14 (s, 1H), 8.11
(dd, J = 19.4, 8.3 Hz, 4H), 3.10 (s, 3H) ppm. 13C{1H} NMR (101
MHz, CDCl3) δ 190.8, 145.5, 139.8, 130.5, 128.4, 44.4 ppm. The
spectroscopic data agree with the literature.56
1
cyclohexane/ethyl acetate (6:4) to obtain 51% yield (180 mg). H
NMR (500 MHz, CDCl3) δ 8.19 (dd, J = 7.7, 1.9 Hz, 1H), 7.77 (dd, J
= 7.8, 1.3 Hz, 1H), 7.50 (dtd, J = 17.1, 7.5, 1.5 Hz, 2H), 3.28 (s, 3H)
ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 139.8, 135.6, 134.9, 131.3,
128.2, 120.8, 42.5 ppm. The spectroscopic data agree with the
literature.42
1-Chloro-2-(methylsulfonyl)benzene (3n). Compound 3n was
synthesized following GP2 using (2-chlorophenyl)(methyl)sulfane
(1n, 238 mg, 1.5 mmol) to give the product as a white solid. It was
purified by column chromatography on silica gel using cyclohexane/
ethyl acetate (6:4) to obtain 53% yield (152 mg). Mp: 82−84 °C [lit.
80−82 °C].42 1H NMR (500 MHz, CDCl3) δ 8.13 (dd, J = 8.3, 1.5
Hz, 1H), 7.59−7.52 (m, 2H), 7.49−7.43 (m, 1H), 3.26 (s, 3H) ppm.
13C{1H} NMR (126 MHz, CDCl3) δ 138.1, 134.9, 132.6, 132.0,
130.9, 127.6, 42.8 ppm. The spectroscopic data agree with the
literature.42
1-Iodo-2-(methylsulfonyl)benzene (3o). Compound 3o was
synthesized following GP2 using (2-iodophenyl)(methyl)sulfane (1o,
375 mg, 1.5 mmol) to give the product as a white solid. It was purified
by column chromatography on silica gel using cyclohexane/ethyl
1
acetate (6:4) to obtain 15% yield (64 mg). Mp: 108−109 °C. H
NMR (500 MHz, CDCl3) δ 8.23 (dd, J = 7.9, 1.7 Hz, 1H), 8.11 (dd, J
= 7.9, 1.2 Hz, 1H), 7.58−7.54 (m, 1H), 7.27 (dt, J = 7.7, 1.7 Hz, 1H),
3.26 (s, 3H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 142.9, 142.9,
134.6, 131.0, 129.0, 92.7, 42.0 ppm. The spectroscopic data agree with
the literature.59
1,3-Dichloro-5-(methylsulfonyl)benzene (3p). Compound 3p
was synthesized following GP2 using (3,5-dichlorophenyl)(methyl)-
sulfane (1n, 290 mg, 1.5 mmol) to give the product as a white solid. It
was purified by column chromatography on silica gel using
cyclohexane/ethyl acetate (6:4) to obtain 60% yield (204 mg). Mp:
202−205 °C [lit. 201−203 °C].25 1H NMR (500 MHz, CDCl3) δ
7.82 (d, J = 1.9 Hz, 2H), 7.62 (t, J = 1.9 Hz, 1H), 3.08 (s, 3H) ppm.
13C{1H} NMR (126 MHz, CDCl3) δ 14.4, 136.5, 133.9, 126.0, 44.5
ppm. The spectroscopic data agree with the literature.25
(Ethylsulfonyl)benzene (3q). Compound 3q was synthesized
following GP2 using ethyl(phenyl)sulfane (1q, 207 mg, 1.5 mmol) to
give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (6:4)
to obtain 74% yield (188 mg). 1H NMR (500 MHz, CDCl3) δ 7.94−
1-(Methylsulfonyl)-4-nitrobenzene (3i). Compound 3i was
synthesized following GP2 using methyl(4-nitrophenyl)sulfane (1i,
254 mg, 1.5 mmol) to give the product as a yellow oil. It was purified
by column chromatography on silica gel using cyclohexane/ethyl
1
acetate (6:4) to obtain 28% yield (85 mg). H NMR (500 MHz,
CDCl3) δ 8.46−8.39 (m, 2H), 8.20−8.10 (m, 2H), 3.12 (s, 3H) ppm.
13C{1H} NMR (101 MHz, CDCl3) δ 151.0, 146.1, 129.1, 124.8, 44.5
ppm. The spectroscopic data agree with the literature.49
1-Methyl-3-(methylsulfonyl)benzene (3j). Compound 3k was
synthesized following GP2 using methyl(m-tolyl)sulfane (1j, 207 mg,
1.5 mmol) to give the product as a colorless oil. It was purified by
H
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7.80 (m, 2H), 7.68−7.51 (m, 3H), 3.10 (q, J = 7.4 Hz, 2H), 1.25 (t, J
= 7.4 Hz, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 138.6,
133.8, 129.3, 128.3, 50.7, 7.5 ppm. The spectroscopic data agree with
the literature.49
column chromatography on silica gel using ethyl acetate (100%) to
1
obtain 51% yield (102 mg). H NMR (500 MHz, CDCl3) δ 3.01−
2.88 (m, 4H), 2.10−2.00 (m, 4H), 1.63−1.55 (m, 2H) ppm. 13C{1H}
NMR (101 MHz, CDCl3) δ 52.16, 24.28, 23.8 ppm. The
spectroscopic data agree with the literature.49
(Propylsulfonyl)benzene (3r). Compound 3r was synthesized
following GP2 using phenyl(propyl)sulfane (1r, 228 mg, 1.5 mmol)
to give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (6:4) to
1,4-Oxathiane 4,4-dioxide (3aa). Compound 3aa was synthe-
sized following GP2 using 1,4-oxathiane (1aa, 156 mg, 1.5 mmol) to
give the product as a white solid. It was purified by column
chromatography on silica gel using ethyl acetate (100%) to obtain
48% yield (98 mg). Mp: 130−132 °C [lit. 130−131 °C].65 1H NMR
(500 MHz, CDCl3) δ 4.14−4.08 (m, 2H), 3.13−3.05 (m, 2H) ppm.
13C{1H} NMR (101 MHz, CDCl3) δ 66.3, 53.0 ppm. The
spectroscopic data agree with the literature.66
1
obtain 71% yield (196 mg). H NMR (500 MHz, CDCl3) δ 7.90−
7.84 (m, 2H), 7.64−7.59 (m, 1H), 7.56−7.51 (m, 2H), 3.06−3.00
(m, 2H), 1.75−1.66 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 139.2, 133.7, 129.3, 128.0, 57.9, 16.5,
12.9 ppm. The spectroscopic data agree with the literature.60
(Cyclopropylsulfonyl)benzene (3s). Compound 3s was synthe-
sized following GP2 using cyclopropyl(phenyl)sulfane (1s, 225 mg,
1.5 mmol) to give the product as a yellow oil. It was purified by
column chromatography on silica gel using cyclohexane/ethyl acetate
(6:4) to obtain 72% yield (198 mg). 1H NMR (500 MHz, CDCl3) δ
7.93−7.80 (m, 2H), 7.65−7.58 (m, 1H), 7.57−7.47 (m, 2H), 2.51−
2.36 (m, 1H), 1.35−1.27 (m, 2H), 1.04−0.94 (m, 2H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 140.7, 133.4, 129.3, 127.5, 32.9, 6.0 ppm.
The spectroscopic data agree with the literature.42
N-(Methyl(oxo)(phenyl)-λ6-sulfaneylidene)cyanamide (5a).
Compound 5a was synthesized following GP3 using (methylsulfinyl)-
benzene (2a, 70 mg, 0.5 mmol) to give the product as a yellow oil. It
was purified by column chromatography on silica gel using
1
cyclohexane/ethyl acetate (4:6) to obtain 46% yield (42 mg). H
NMR (500 MHz, CDCl3) δ 7.98−7.89 (m, 2H), 7.76−7.70 (m, 1H),
7.66−7.60 (m, 2H), 3.28 (s, 3H) ppm. 13C{1H} NMR (126 MHz,
CDCl3) δ 136.1, 135.6, 130.4, 128, 112, 44.9 ppm. The spectroscopic
data agree with the literature.67
(Allylsulfonyl)benzene (3t). Compound 3t was synthesized
following GP2 using allyl(phenyl)sulfane (1t, 225 mg, 1.5 mmol to
give the product as a colorless oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (6:4) to
obtain 18% yield (48 mg). 1H NMR (500 MHz, CDCl3) δ 7.91−7.82
(m, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.56 (t, J = 7.7 Hz, 2H), 5.80 (ddt,
J = 17.4, 10.1, 7.4 Hz, 1H), 5.24 (dd, J = 92.6, 13.6 Hz, 2H), 3.81 (d, J
= 7.4 Hz, 2H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 138.4,
133.9, 129.2, 128.7, 124.9, 124.8, 61.0 ppm. The spectroscopic data
agree with the literature.61
N-(Methyl(oxo)(p-tolyl)-λ6-sulfaneylidene)cyanamide (5b).
Compound 5b was synthesized following GP3 using 1-methyl-4-
(methylsulfinyl)benzene (2b, 77 mg, 0.5 mmol) to give the product as
a yellow oil. It was purified by column chromatography on silica gel
using cyclohexane/ethyl acetate (4:6) to obtain 42% yield (41 mg).
1H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 8.3 Hz, 2H), 7.47 (d, J =
8.2 Hz, 2H), 3.31 (s, 3H), 2.49 (s, 3H) ppm. 13C{1H} NMR (126
MHz, CDCl3) δ 147.2, 133.0, 131.0, 128.1, 112.2, 45.1, 21.9 ppm.
The spectroscopic data agree with the literature.65
N-((4-Bromophenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5c). Compound 5c was synthesized following GP3
using 1-bromo-4-(methylsulfinyl)benzene (2c, 110 mg, 0.5 mmol) to
give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6)
Sulfonyldibenzene (3v). Compound 3v was synthesized
following GP2 using diphenylsulfane (1v, 279 mg, 1.5 mmol) to
give the product as a white solid. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (6:4) to
obtain 70% yield (230 mg). Mp: 121−122 °C [lit. 117−118 °C].62
1H NMR (400 MHz, CDCl3) δ 8.02−7.89 (m, 2H), 7.61−7.46 (m,
3H) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ 141.7, 133.3, 129.4,
127.8 ppm. The spectroscopic data agree with the literature.42
Thiochroman-4-one 1,1-dioxide (3w). Compound 3w was
synthesized following GP2 using thiochroman-4-one (1w, 246 mg, 1.5
mmol) to give the product as a white solid. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (6:4) to
obtain 48% yield (142 mg). Mp: 142−144 °C [lit. 142−144 °C].63
1H NMR (500 MHz, CDCl3) δ 8.09 (d, J = 7.8 Hz, 1H), 7.98 (d, J =
7.8 Hz, 1H), 7.80 (t, J = 7.6 Hz, 1H), 7.72 (t, J = 7.7 Hz, 1H), 3.77−
3.61 (m, 2H), 3.46−3.30 (m, 2H) ppm. 13C{1H} NMR (126 MHz,
CDCl3) δ 190.26, 141.5, 135.0, 133.5, 130.3, 128.9, 123.7, 49.3, 36.8
ppm. The spectroscopic data agree with the literature.64
1
to obtain 43% yield (56 mg). H NMR (500 MHz, CDCl3) δ 7.93−
7.78 (m, 4H), 3.35 (s, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3)
δ 135.1, 133.8, 131.4, 129.5, 111.6, 44.8 ppm. The spectroscopic data
agree with the literature.65
N-((4-Chlorophenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5d). Compound 5d was synthesized following GP3
using 1-chloro-4-(methylsulfinyl)benzene (2d, 87 mg, 0.5 mmol) to
give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6)
1
to obtain 48% yield (52 mg). H NMR (500 MHz, CDCl3) δ 8.00−
7.88 (m, 2H), 7.72−7.61 (m, 2H), 3.35 (s, 3H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 142.8, 134.5, 130.8, 129.5, 111.6, 45.0 ppm.
The spectroscopic data agree with the literature.65
N-((4-Fluorophenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5e). Compound 5e was synthesized following GP3,
starting with 1-fluoro-4-(methylsulfinyl)benzene (2e, 79 mg, 0.5
mmol) to give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6) to
obtain 36% yield (36 mg). 1H NMR (500 MHz, CDCl3) δ 8.06−8.00
(m, 2H), 7.39−7.33 (m, 2H), 3.35 (s, 3H) ppm. 13C{1H} NMR (126
MHz, CDCl3) δ 167.0 (d, J = 260.2 Hz), 132.0 (d, J = 3.2 Hz), 131.2
(d, J = 10.1 Hz), 118.0 (d, J = 23.1 Hz). 112.0, 45.1 ppm. 19F NMR
(471 MHz, CDCl3) δ − 99.69 ppm. The spectroscopic data agree
with the literature.68
N-((4-Cyanophenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5f). Compound 5f was synthesized following GP3 using
4-(methylsulfinyl)benzonitrile (2f, 83 mg, 0.5 mmol) to give the
product as a yellow oil. It was purified by column chromatography on
silica gel using cyclohexane/ethyl acetate (4:6) to obtain 44% yield
(45 mg). 1H NMR (500 MHz, CDCl3) δ 8.18−8.11 (m, 2H), 8.02−
7.95 (m, 2H), 3.40 (s, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3)
δ 140.4, 134.0, 128.9, 119.4, 116.6, 111.0, 44.5 ppm. The
spectroscopic data agree with the literature.69
2-(Methylsulfonyl)pyridine (3x). Compound 3x was synthesized
following GP2 using 2-(methylthio)pyridine (1x, 188 mg, 1.5 mmol)
to give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6) to
1
obtain 67% yield (158 mg). H NMR (500 MHz, CDCl3) δ 8.75−
8.69 (m, 1H), 8.07 (dt, J = 7.9, 1.0 Hz, 1H), 7.96 (td, J = 7.8, 1.7 Hz,
1H), 7.55 (ddd, J = 7.7, 4.7, 1.1 Hz, 1H), 3.21 (s, 3H) ppm. 13C{1H}
NMR (101 MHz, CDCl3) δ 158.1, 150.1, 138.4, 127.6, 121.1, 40.1
ppm. The spectroscopic data agree with the literature.42
1-(Butylsulfonyl)butane (3y). Compound 3y was synthesized
following GP2 using dibutylsulfane (1y, 219 mg, 1.5 mmol) to give
the product as a colorless oil. It was purified by column
chromatography on silica gel using ethyl acetate (100%) to obtain
1
34% yield (92 mg). H NMR (500 MHz, CDCl3) δ 3.11−2.80 (m,
2H), 1.84−1.76 (m, 2H), 1.50−1.42 (m, 2H), 0.95 (t, J = 7.4 Hz,
3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 52.6, 24.0, 21.9, 13.7
ppm. The spectroscopic data agree with the literature.49
Tetrahydro-2H-thiopyran 1,1-dioxide (3z). Compound 3z was
synthesized following GP2 using tetrahydro-2H-thiopyran (1z, 153
mg, 1.5 mmol) to give the product as a colorless oil. It was purified by
I
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N-((4-Methoxyphenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5g). Compound 5g was synthesized following GP3
using 1-methoxy-4-(methylsulfinyl)benzene (2g, 85 mg, 0.5 mmol) to
give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6)
(m, 1H), 1.40−1.28 (m, 2H), 1.15−1.08 (m, 1H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 136.5, 135.2, 130.2, 128.0, 112.2, 33.7,
7.2, 6.1 ppm. The spectroscopic data agree with the literature.65
N-(Oxodiphenyl-λ6-sulfaneylidene)cyanamide (5p). Com-
pound 5p was synthesized following GP3 using sulfinyldibenzene
(2v, 101 mg, 0.5 mmol) to give the product as a yellow oil. It was
purified by column chromatography on silica gel using cyclohexane/
ethyl acetate (4:6) to obtain 23% yield (28 mg). 1H NMR (500 MHz,
CDCl3) δ 7.72−7.64 (m, 2H), 7.63−7.55 (m, 3H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 135.8, 133.1, 130.4, 127.6, 113.8 ppm.
The spectroscopic data agree with the literature.65
N-(Methyl(oxo)(pyridin-2-yl)-λ6-sulfaneylidene)cyanamide
(5q). Compound 5q was synthesized following GP3 using 2-
(methylsulfinyl)pyridine (2x, 101 mg, 0.5 mmol) to give the product
as a yellow oil. It was purified by column chromatography on silica gel
using cyclohexane/ethyl acetate (4:6) to obtain 35% yield (32 mg).
1H NMR (500 MHz, CDCl3) δ 8.75 (d, J = 4.7 Hz, 1H), 8.10 (d, J =
7.8 Hz, 1H), 7.99 (td, J = 7.8, 1.6 Hz, 1H), 7.62−7.53 (m, 1H), 3.24
(s, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 158.2, 150.6,
138.8, 128.0, 121.6, 113.7, 40.5 ppm. The spectroscopic data agree
with the literature.65
N-(1-Oxidotetrahydro-2H-1λ6-thiopyran-1-ylidene)-
cyanamide (5r). Compound 5r was synthesized following GP3 using
tetrahydro-2H-thiopyran 1-oxide (2z, 59 mg, 0.5 mmol) to give the
product as a yellow oil. It was purified by column chromatography on
silica gel using ethyl acetate (100%) to obtain 52% yield (41 mg). 1H
NMR (500 MHz, CDCl3) δ 3.60−3.37 (m, 2H), 3.34−3.08 (m, 2H),
2.23−2.04 (m, 4H), 1.80−1.57 (m, 2H) ppm. 13C{1H} NMR (126
MHz, CDCl3) δ 112.2, 51.8, 23.8, 22.9 ppm. IR (neat): 2148, 1416,
1174, 872, 756 cm-1 cm−1. HRMS (ESI) m/z: [M + H] calcd for
C6H11N2OS 159.0592; found, 159.0593.
1
to obtain 32% yield (34 mg). H NMR (500 MHz, CDCl3) δ 8.01−
7.80 (m, 2H), 7.18−7.03 (m, 2H), 3.92 (s, 3H), 3.32 (s, 3H) ppm.
13C{1H} NMR (126 MHz, CDCl3) δ 165.4, 130.4, 126.6, 115.7,
113.8, 56.2, 45.4 ppm. The spectroscopic data agree with the
literature.65
N-((3-Bromophenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5h). Compound 5h was synthesized following GP3
using 1-bromo-3-(methylsulfinyl)benzene (2k, 110 mg, 0.5 mmol) to
give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6)
to obtain 37% yield (48 mg). 1H NMR (500 MHz, CDCl3) δ 8.12 (s,
1H), 7.97−7.88 (m, 2H), 7.57 (t, J = 8.0 Hz, 1H), 3.36 (s, 3H) ppm.
13C{1H} NMR (126 MHz, CDCl3) δ 138.7, 138.0, 131.8, 130.8,
126.6, 124.4, 111.4, 44.9 ppm. The spectroscopic data agree with the
literature.65
N-((3-Chlorophenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5i). Compound 5i was synthesized following GP3 using
1-chloro-3-(methylsulfinyl)benzene (2l, 87 mg, 0.5 mmol) to give the
product as a yellow oil. It was purified by column chromatography on
silica gel using cyclohexane/ethyl acetate (4:6) to obtain 42% yield
1
(45 mg). H NMR (500 MHz, CDCl3) δ 7.97 (t, J = 1.9 Hz, 1H),
7.89 (ddd, J = 7.9, 1.9, 1.0 Hz, 1H), 7.75 (ddd, J = 8.1, 2.0, 1.0 Hz,
1H), 7.64 (t, J = 8.0 Hz, 1H), 3.36 (s, 3H) ppm. 13C{1H} NMR (101
MHz, CDCl3) δ 137.9, 136.8, 135.8, 131.7, 128.1, 126.1, 111.4, 44.8
ppm. The spectroscopic data agree with the literature.70
N-((3,5-Dichlorophenyl)(methyl)(oxo)-λ6-sulfaneylidene)-
cyanamide (5l). Compound 5l was synthesized following GP3 using
1,3-dichloro-5-(methylsulfinyl)benzene (2p, 105 mg, 0.5 mmol) to
give the product as a yellow oil. It was purified by column
chromatography on silica gel using cyclohexane/ethyl acetate (4:6)
to obtain 29% yield (36 mg). 1H NMR (500 MHz, CDCl3) δ 7.87 (d,
J = 1.8 Hz, 2H), 7.75 (t, J = 1.8 Hz, 1H), 3.38 (s, 3H) ppm. 13C{1H}
NMR (126 MHz, CDCl3) δ 139.1, 137.5, 135.7, 126.4, 110.9, 44.7
ppm. IR (neat): 2934, 2185, 1444, 1211, 1167, 1091, 844, 688 cm−1.
HRMS (ESI) m/z: [M + H] calcd for C8H7N2OSCl2, 248.9656;
found, 248.9655.
Imino(methyl)(phenyl)-λ6-sulfanone (6a). Compound 6a was
synthesized following GP4 using N-(methyl(oxo)(phenyl)-λ6-
sulfaneylidene)cyanamide (5a, 90 mg, 0.5 mmol) to give the product
as a colorless oil. It was purified by column chromatography on silica
gel using ethyl acetate (100%) to obtain 68% yield (53 mg). 1H NMR
(500 MHz, CDCl3) δ 8.02−7.90 (m, 2H), 7.61−7.55 (m, 1H), 7.55−
7.45 (m, 2H), 3.06 (s, 3H), 2.70 (s, 1H) ppm. 13C{1H} NMR (126
MHz, CDCl3) δ 143.5, 133.1, 129.3, 127.7, 46.2 ppm. The
spectroscopic data agree with the literature.71
Imino(methyl)(p-tolyl)-λ6-sulfanone (6b). Compound 6b was
synthesized following GP4, using N-(methyl(oxo)(p-tolyl)-λ6-
sulfaneylidene)cyanamide (5b, 97 mg, 0.5 mmol) to give the product
as pale-yellow oil. It was purified by column chromatography on silica
gel using ethyl acetate (100%) to obtain 74% yield (63 mg). 1H NMR
(500 MHz, CDCl3) δ 7.87 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.3 Hz,
2H), 3.08 (br.s, 3H), 2.94 (s, 1H), 2.43 (s, 3H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 144.1, 140.6, 130.0, 127.9, 46.4, 21.6 ppm. The
spectroscopic data agree with the literature.69
Ethyl(imino)(phenyl)-λ6-sulfanone (6m). Compound 6m was
synthesized following GP4 using N-(ethyl(oxo)(phenyl)-λ6-
sulfaneylidene)cyanamide (5m, 97 mg, 0.5 mmol) to give the product
as pale-yellow oil. It was purified by column chromatography on silica
gel using ethyl acetate (100%) to obtain 72% yield (61 mg). 1H NMR
(500 MHz, CDCl3) δ 7.96−7.86 (m, 2H), 7.59−7.54 (m, 1H), 7.52−
7.46 (m, 2H), 3.12 (q, J = 7.5 Hz, 2H), 2.69 (s, 1H), 1.20 (t, J = 7.4
Hz, 3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 141.3, 133.0,
129.1, 128.5, 51.8, 7.9 ppm. The spectroscopic data agree with the
literature.69
N-(Ethyl(oxo)(phenyl)- λ6-sulfaneylidene)cyanamide (5m).
Compound 5m was synthesized following GP3 using (ethylsulfinyl)-
benzene (2q, 77 mg, 0.5 mmol) to give the product as a yellow oil. It
was purified by column chromatography on silica gel using
1
cyclohexane/ethyl acetate (4:6) to obtain 43% yield (42 mg). H
NMR (500 MHz, CDCl3) δ 7.98−7.90 (m, 2H), 7.82−7.77 (m, 1H),
7.71−7.66 (m, 2H), 3.52−3.33 (m, 2H), 1.34 (t, J = 7.4 Hz, 3H)
ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 135.6, 134.0, 130.3, 128.7,
112.3, 51.7, 7.3 ppm. The spectroscopic data agree with the
literature.66
N-(Oxo(phenyl)(propyl)-λ6-sulfaneylidene)cyanamide (5n).
Compound 5n was synthesized following GP3 using (propylsulfinyl)-
benzene (2r, 84 mg, 0.5 mmol) to give the product as a yellow oil. It
was purified by column chromatography on silica gel using
1
cyclohexane/ethyl acetate (4:6) to obtain 40% yield (42 mg). H
NMR (500 MHz, CDCl3) δ 8.01−7.88 (m, 2H), 7.80−7.75 (m, 1H),
7.71−7.64 (m, 2H), 3.40 (ddd, J = 14.2, 10.6, 5.4 Hz, 1H), 3.30 (ddd,
J = 14.2, 10.5, 5.5 Hz, 1H), 1.87−1.72 (m, 2H), 1.02 (t, J = 7.5 Hz,
3H) ppm. 13C{1H} NMR (126 MHz, CDCl3) δ 135.5, 134.8, 130.3,
128.6, 112.3, 58.4, 16.3, 12.6 ppm. IR (neat): 2923, 2191, 1447, 1241,
1186, 1091, 825, 683 cm−1. HRMS (ESI) m/z: [M + H] calcd for
C10H13N2OS 209.0749; found, 209.0746.
N-(Cyclopropyl(oxo)(phenyl)-λ6-sulfaneylidene)cyanamide
(5o). Compound 5o was synthesized following GP3 using
(cyclopropylsulfinyl)benzene (2s, 83 mg, 0.5 mmol) to give the
product as a yellow oil. It was purified by column chromatography on
silica gel using cyclohexane/ethyl acetate (4:6) to obtain 38% yield
(39 mg). 1H NMR (500 MHz, CDCl3) δ 8.02−7.87 (m, 2H), 7.78−
7.74 (m, 1H), 7.69−7.61 (m, 2H), 2.73−2.65 (m, 1H), 1.72−1.65
Imino(methyl)(pyridin-2-yl)-λ6-sulfanone (6q). Compound
6q was synthesized following GP4 using N-(methyl(oxo)(pyridin-2-
yl)-λ6-sulfaneylidene)cyanamide (5q, 97 mg, 0.5 mmol) to give the
product as pale-yellow oil. It was purified by column chromatography
on silica gel using CH2Cl2/MeOH (20:1) to obtain 51% yield (40
1
mg). H NMR (500 MHz, CDCl3) δ 8.72 (d, J = 4.7 Hz, 1H), 8.12
(dt, J = 7.9, 1.0 Hz, 1H), 7.94 (td, J = 7.8, 1.7 Hz, 1H), 7.50 (ddd, J =
7.6, 4.7, 1.1 Hz, 1H), 3.25 (s, 3H), 2.73 (s, 1H) ppm. 13C{1H} NMR
(126 MHz, CDCl3) δ 160.6, 150.7, 138.4, 126.9, 121.2, 42.4 ppm.
The spectroscopic data agree with the literature.39
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00860.
■
sı
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ChemSusChem 2020, 13, 922−928.
Automated flow and electrochemical reactor setup,
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AUTHOR INFORMATION
Corresponding Author
Thomas Wirth − School of Chemistry, Cardiff University,
Cardiff CF10 3AT, United Kingdom; orcid.org/0000-
0002-8990-0667; Email: wirth@cf.ac.uk
■
(17) Organic Electrochemistry; Hammerich, O., Speiser, B., Eds.;
CRC Press, 2015.
Author
(18) Fundamentals and Applications of Organic Electrochemistry;
Fuchigami, T., Inagi, S., Atobe, M., Eds.; John Wiley & Sons Ltd:
Chichester, United Kingdom, 2014.
Nasser Amri − School of Chemistry, Cardiff University, Cardiff
CF10 3AT, United Kingdom
(19) Yoshida, J.; Kataoka, K.; Horcajada, R.; Nagaki, A. Modern
Strategies in Electroorganic Synthesis. Chem. Rev. 2008, 108, 2265−
2299.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00860
(20) Waldvogel, S. R.; Janza, B. Renaissance of Electrosynthetic
Methods for the Construction of Complex Molecules. Angew. Chem.,
Int. Ed. 2014, 53, 7122−7123.
Notes
The authors declare no competing financial interest.
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Electrochemical Methods Since 2000: On the Verge of a Renaissance.
Chem. Rev. 2017, 117, 13230−13319.
ACKNOWLEDGMENTS
■
We thank D. Guthrie and M. Nuno, Vapourtec Inc., for many
discussions and for providing some of the equipment and
support for this research. Support from Cardiff University and
from the Chemistry Department, Jazan University, Saudi
Arabia, is greatly appreciated.
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Waldvogel, S. R. Modern Electrochemical Aspects for the Synthesis of
Value-Added Organic Products. Angew. Chem., Int. Ed. 2018, 57,
6018−6041.
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Vasquez-Medrano, R. Organic Electrosynthesis: A Promising Green
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