Electrosynthesis of Arylsulfonamides from Amines and Sodium Sulfinates Using H2O-NaI as the Electrolyte Solution at Room Temperature

Article abstract of DOI:10.1002/cjoc.201600452

With H₂O as the solvent and NaI as the supporting electrolyte, a green and efficient electrochemical route has been developed to synthesize arylsulfonamides via I₂electrogenerated in situ at a graphite anode to promote the reaction of sodium sulfinates with aromatic or aliphatic primary and secondary amines. The target products could be obtained in good to excellent yields at room temperature.

Full text of DOI:10.1002/cjoc.201600452

FULL PAPER
DOI: 10.1002/cjoc.201600452
Electrosynthesis of Arylsulfonamides from Amines and
Sodium Sulfinates Using H O-NaI as the Electrolyte
2
Solution at Room Temperature
Chen Zhang, Yibin Chen, and Gaoqing Yuan*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical
Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China
With H O as the solvent and NaI as the supporting electrolyte, a green and efficient electrochemical route has
2
been developed to synthesize arylsulfonamides via I electrogenerated in situ at a graphite anode to promote the re-
2
action of sodium sulfinates with aromatic or aliphatic primary and secondary amines. The target products could be
obtained in good to excellent yields at room temperature.
Keywords sulfonamindes, I -promoted, sodium sulfinates, electrosynthesis
2
Introduction
have received considerable attention in organic synthe-
[
6]
sis. Our group has been interested in electrochemical
synthesis. With I electrogenerated in situ as a promoter
Sulfonamides, existing widely in natural products,
are a class of important compounds with unique biolog-
ical activity. Some investigations have indicated that
sulfonamides could be used as hypoglycemic, diuretic,
2
or inducer, some organic transformations were smoothly
[7]
achieved under mild conditions. In this paper, we re-
port a green and efficient electrochemical route for the
synthesis of arylsulfonamides using H O as the solvent
2
and NaI as the supporting electrolyte at room tempera-
ture (Scheme 1).
[1]
antibiotic and anticancer drugs. In the recent decade,
much attention has been paid to the synthesis of sul-
fonamides. Traditional preparation of sulfonamides in-
volves reactions of sulfonyl chlorides or thiols with
amino compounds and sulfonamides with organic hal-
ides, hydrocarbons or alcohols via metal-catalyzed cou-
Scheme 1 Different routes for the synthesis of sulfonamides
[2]
[3a]
pling process. Recently, Jiang et al. has developed a
new and attractive protocol for the synthesis of sulfon-
2
amides via CuBr -catalyzed reaction of sodium sul-
finates with amines (Scheme 1). Although much pro-
[3]
gress has been made in the synthesis of sulfonamides,
some drawbacks still exist such as the need of toxic
solvents or transition metal catalysts, and tedious puri-
fication procedures of products. Therefore, developing a
green process for the synthesis of sulfonamides is still
highly desired. Some researchers and our group have
2
further investigated I -promoted reaction of sodium sul-
finates with amines to synthesize sulfonamides at room
[
4]
[5]
temperature (Scheme 1). More recently, Yu et al.
reported the synthesis of sulfonamides from aryl-
sulfonylhydrazides and amines using TBHP as the oxi-
dant and NH I (20 mol%) as the catalyst.
4
Electrochemical methods are considered to be envi-
ronmentally friendly since toxic or dangerous stoichio-
metric oxidants/reductants are replaced with simple
electrical current. Recently, electrochemical methods
*
E-mail: gqyuan@scut.edu.cn
Received July 20, 2016; accepted October 3, 2016; published online XXXX, 2016.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201600452 or from the author.
Chin. J. Chem. 2016, XX, 1—6
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Zhang et al.
FULL PAPER
Experimental
General
4.94 (br, 1H), 4.04 (s, 2H), 2.42 (s, 3H), 2.29 (s, 3H);
C NMR (100 MHz, CDCl ) δ: 143.4, 137.6, 136.9,
3
33.3, 129.7, 129.3, 127.9, 127.2, 47.0, 21.5, 21.1.
N-(4-Chlorobenzyl)-4-methylbenzenesulfonamide
H NMR (400 MHz, CDCl ) δ: 7.70 (d, J＝
3
7.3 Hz, 2H), 7.26 (d, J＝6.3 Hz, 2H), 7.19 (d, J＝7.3 Hz,
2H), 7.11 (d, J＝7.8 Hz, 2H), 5.34 (br, 1H), 4.05 (d, J＝
1
3
1
1
13
H NMR and C NMR spectra were determined on
a Bruker Advance 400 spectrometer in CDCl at 400 and
00 MHz, respectively. Chloroform is used as the sol-
[2j]
1
3
(3d a)
3
1
vent with TMS as the internal standard, and the chemi-
cal shifts are referenced to signals at 7.26 and 77.0, re-
spectively. Mass spectra were detected on a Shimadzu
GC-MS-QP5050A spectrometer at an ionization voltage
of 70 eV equipped with a DB-WAX capillary column
13
5.0 Hz, 2H), 2.42 (s, 3H); C NMR (100 MHz, CDCl )
3
δ: 143.7, 136.8, 135.0, 133.6, 129.8, 129.3, 128.7, 127.1,
46.5, 21.5.
[3a]
4-Methyl-N-phenylbenzenesulfonamide (3e a)
1
1
(
internal diameter: 0.25 mm, length: 30 m).
3
H NMR (400 MHz, CDCl ) δ: 7.71 (d, J＝8.2 Hz, 2H),
7
2
.59 (s, 1H), 7.19 (t, J＝8.0 Hz, 4H), 7.11 (d, J＝8.5 Hz,
H), 7.05 (t, J＝7.2 Hz, 1H), 2.32 (s, 3H); C NMR
A typical procedure for the synthesis of arylsulfona-
mides
13
(
1
100 MHz, CDCl
3
) δ: 143.8, 136.6, 135.9, 129.6, 129.2,
27.2, 125.0, 121.2, 21.4.
-Methyl-N-(p-tolyl)benzenesulfonamide (3e
H NMR (400 MHz, CDCl ) δ: 7.66 (d, J＝7.9 Hz, 2H),
.25 (br, 1H), 7.19 (d, J＝7.8 Hz, 2H), 7.01－6.96 (m,
In a typical procedure, an undivided cell was
equipped with a Ni cathode (2 cm×2.5 cm×0.02 cm)
and a graphite rod anode. H O (10 mL), amines (1
2
[2k]
4
2
a)
1
3
mmol), sodium sulfinates (1.0 mmol) and NaI (4 mmol)
were in turn added to the undivided cell. The electroly-
sis was carried out in the undivided cell with constant
current (50 mA) for 1 h at room temperature. After the
electrolysis, the electrolyzed solution was continuously
stirred for 3 h so that sodium sulfinate with amine could
be completely converted to the target product. Then, the
solution was extracted with ethyl acetate (10 mL×3),
and the obtained organic layer was dried with anhydrous
7
4
13
H), 2.34 (s, 3H), 2.24 (s, 3H); C NMR (100 MHz,
) δ: 143.7, 136.1, 135.2, 133.9, 129.8, 129.6,
27.4, 122.1, 21.5, 20.9.
N-(4-Bromophenyl)-4-methylbenzenesulfonamide
CDCl
1
3
[
2i]
1
(
3e
3
a)
3
H NMR (400 MHz, CDCl ) δ: 7.67 (d, J＝
7
.5 Hz, 2H), 7.33 (d, J＝7.5 Hz, 2H), 7.26 (br, 1H), 7.23
(
d, J＝7.8 Hz, 2H), 6.97 (d, J＝7.5 Hz, 2H), 2.38 (s,
1
3
3
1
H); C NMR (100 MHz, CDCl
3
) δ: 144.2, 135.7,
4
MgSO . The solvent was removed by rotavapor under
35.7, 132.4, 129.8, 127.3, 123.0, 118.5, 21.56.
[
3a]
1
reduced pressure. The obtained crude product was puri-
fied by column chromatography on silica gel with pe-
troleum ether/ethyl acetate (5∶1) as eluent.
N,4-Dimethylbenzenesulfonamide (3f
NMR (400 MHz, CDCl ) δ: 7.75 (d, J＝8.1 Hz, 2H),
.32 (d, J＝8.0 Hz, 2H), 4.64 (br, 1H), 2.64 (d, J＝5.0
1
a)
H
3
7
[3a]
1
13
4
-Tosylmorpholine (3aa)
H NMR (400 MHz,
Hz, 3H), 2.43 (s, 3H); C NMR (100 MHz, CDCl
1
3
) δ:
CDCl
3
) δ: 7.64 (d, J＝8.1 Hz, 2H), 7.35 (d, J＝8.0 Hz,
43.5, 135.8, 129.7, 127.2, 29.3, 21.5.
N-Ethyl-4-methylbenzenesulfonamide
[
3a]
2
2
1
H), 3.73 (t, J＝4.8 Hz,4H), 2.98 (t, J＝4.8 Hz, 4H),
2
(3f a)
13
1
.44 (s, 3H); C NMR (100 MHz, CDCl
32.1, 129.8, 127.9, 66.1, 46.0, 21.5.
3
) δ: 143.9,
H NMR (400 MHz, CDCl
3
) δ: 7.76 (d, J＝8.2 Hz, 2H),
7
2
.31 (d, J＝8.1 Hz, 2H), 4.61 (s, 1H), 3.03－2.96 (m,
1
3
N-(2-Hydroxyethyl)-N,4-dimethylbenzenesulfona-
H), 2.43 (s, 3H), 1.10 (t, J＝7.2 Hz, 3H); C NMR
) δ: 143.3, 137.0, 129.7, 127.1, 38.2,
[3a]
1
mide (3ba)
3
H NMR (400 MHz, CDCl ) δ: 7.68 (d,
(
100 MHz, CDCl
3
J＝7.9 Hz, 2H), 7.33 (d, J＝7.8 Hz, 2H), 3.76 (s, 2H),
2
1.5, 15.0.
N-Butyl-4-methylbenzenesulfonamide
H NMR (400 MHz, CDCl ) δ: 7.75 (d, J＝8.2 Hz, 2H),
.31 (d, J＝8.0 Hz, 2H), 4.56 (s, 1H), 2.96－2.90 (m,
H), 2.43 (s, 3H), 1.47－1.40 (m, 2H), 1.33－1.24 (m,
[
3a]
3
.15 (s, 2H), 2.81 (s, 3H), 2.57 (br, 1H), 2.43 (s, 3H);
3
(3f a)
1
3
1
3
C NMR (100 MHz, CDCl ) δ: 143.7, 134.2, 129.8,
3
1
27.4, 60.2, 52.5, 36.0, 21.5.
7
2
2
N-(Furan-2-ylmethyl)-4-methylbenzenesulfona-
[
2i]
1
13
mide (3ca)
3
H NMR (400 MHz, CDCl ) δ: 7.71 (d,
H), 0.85 (t, J＝7.3 Hz, 3H); C NMR (100 MHz,
J＝7.6 Hz, 2H), 7.27 (d, J＝7.0 Hz, 2H), 7.23 (s, 1H),
.20 (s, 1H), 6.08 (s, 1H), 5.00 (br, 1H), 4.16 (d, J＝5.6
CDCl
1
3
) δ: 143.3, 137.0, 129.6, 127.1, 42.9, 31.6, 21.5,
6
9.7, 13.5.
13
[3a]
Hz, 2H), 2.41 (s, 3H); C NMR (100 MHz, CDCl
3
) δ:
N-tert-Butyl-4-methylbenzenesulfonamide (3f a)
4
1
1
4
49.6, 143.5, 142.5, 136.9, 129.7, 127.2, 110.4, 108.2,
H NMR (400 MHz, CDCl ) δ: 7.77 (d, J＝8.2 Hz, 2H),
3
0.1, 21.5.
7.27 (d, J＝8.3 Hz, 2H), 4.63 (br, 1H), 2.42 (s, 3H),
1.22 (s, 9H); C NMR (100 MHz, CDCl ) δ: 142.8,
140.5, 129.4, 127.0, 54.6, 30.1, 21. 5.
[3a]
13
N-Benzyl-4-methylbenzenesulfonamide (3d
1
a)
3
1
H NMR (400 MHz, CDCl
3
) δ: 7.73 (d, J＝6.6 Hz, 2H),
[3a]
7
2
1
2
.28－7.17 (m, 7H), 5.06 (br, 1H), 4.09 (d, J＝5.7 Hz,
H), 2.41 (s, 3H); C NMR (100 MHz, CDCl ) δ: 143.4,
3
36.8, 136.3, 129.6, 128.6, 127.8, 127.7, 127.1, 47.1,
1.4.
N-Hexyl-4-methylbenzenesulfonamide
5
(3f a)
1
3
1
H NMR (400 MHz, CDCl ) δ: 7.75 (d, J＝8.1 Hz, 2H),
3
7.30 (d, J＝8.0 Hz, 2H), 4.57－4.56 (m, 1H), 2.92 (m,
2H), 2.43 (s, 3H), 1.47－1.40 (m, 2H), 1.26－1.21 (m,
6H), 0.84 (t, J＝6.7 Hz, 3H); C NMR (100 MHz,
13
4
-Methyl-N-(4-methylbenzyl)benzenesulfona-
[
2j]
1
mide (3d
2
a)
H NMR (400 MHz, CDCl
3
) δ: 7.74 (d,
CDCl ) δ: 143.3, 137.0, 129.6, 127.1, 43.2, 31.2, 29.5,
3
J＝8.0 Hz, 2H), 7.28 (d, J＝7.9 Hz, 2H), 7.06 (s, 4H),
26.1, 22.4, 21.5, 13.9.
2
www.cjc.wiley-vch.de
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—6

Electrosynthesis of Arylsulfonamides from Amines and Sodium Sulfinates
[3a]
a
N,4-Dimethyl-N-phenylbenzenesulfonamide (3ga)
H NMR (400 MHz, CDCl ) δ: 7.43 (d, J＝8.1 Hz, 2H),
.28－7.23 (m, 5H), 7.10 (d, J＝7.4 Hz, 2H), 3.16 (s,
Table 1 Optimization of electrolytic conditions
1
3
7
3
1
2
1
3
3
H), 2.42 (s, 3H); C NMR (100 MHz, CDCl ) δ: 143.5,
41.6, 133.6, 129.3, 128.8, 127.9, 127.2, 126.6, 38.1,
1.5.
[3a]
b
N-Benzyl-N,4-dimethylbenzenesulfonamide (3ha)
H NMR (400 MHz, CDCl ) δ: 7.73 (d, J＝8.2 Hz, 2H),
.37－7.29 (m, 7H), 4.13 (s, 2H), 2.58 (s, 3H), 2.45 (s,
Entry Anode-Cathode Supporting electrolyte Solvent Yield /%
1
3
1
2
3
4
5
6
7
8
9
C－Ni
C－Ni
C－Ni
C－Ni
C－Ni
C－Ni
C－Ni
C—Ni
C—Ni
C—Cu
NaI
NaI
DMSO
DMF
95
87
83
94
62
78
91
90
87
92
90
91
7
3
1
2
1
3
3
H); C NMR (100 MHz, CDCl ) δ: 143.4, 135.7,
NaI
DMA
34.4, 129.7, 128.6, 128.4, 127.9, 127.5, 54.1, 34.3,
1.5.
NaI
H O
2
[
3a]
1
1
-(Phenylsulfonyl)pyrrolidine (3ab)
400 MHz, CDCl ) δ: 7.84 (d, J＝7.1 Hz, 2H), 7.62－
.51 (m, 3H), 3.25 (t, J＝6.7 Hz, 4H), 1.77－1.74 (m,
H NMR
NaCl
NaBr
H O
2
(
3
H O
2
7
4
1
NH
4
I
2
H O
1
3
H); C NMR (100 MHz, CDCl
3
) δ: 137.0, 132.5,
n-Bu NI
2
H O
4
29.0, 127.5, 47.9, 25.2.
[3a]
KI
H O
2
4
-((4-Fluorophenyl)sulfonyl)morpholine (3ac)
H NMR (400 MHz, CDCl ) δ: 7.80－7.77 (m, 2H),
.24 (t, J＝8.1 Hz, 2H), 3.74 (d, J＝3.6 Hz, 4H), 3.00 (s,
1
1
0
NaI
NaI
NaI
H O
2
3
c
7
4
1
11
C—SS
C—Ag
2
H O
1
3
H); C NMR (100 MHz, CDCl
31.3, 130.6, 130.5, 116.6, 116.4, 66.1, 46.0.
-((4-Chlorophenyl)sulfonyl)morpholine (3ad)
H NMR (400 MHz, CDCl ) δ: 7.70 (d, J＝8.0 Hz, 2H),
.54 (d, J＝8.3 Hz, 2H), 3.74 (s, 4H), 3.00 (s, 4H); C
NMR (100 MHz, CDCl ) δ: 139.7, 133.7, 129.5, 129.2,
3
) δ: 166.7, 164.1,
12
H O
2
a
Electrolytic conditions: 1a (1 mmol), 2a (1 mmol), solvent (10
[
2h]
4
–1
mL), supporting electrolyte (0.4 mol•L ), undivided cell, elec-
trolysis with constant current 50 mA for 1 h and then continuous-
ly stirring for 3 h at r.t. Determined by GC-MS. Stainless steel.
1
3
13
7
b
c
3

6
6.0, 46.0.
-((4-Bromophenyl)sulfonyl)pyrrolidine (3ae)
H NMR (400 MHz, CDCl ) δ: 7.68 (q, J＝8.7 Hz, 4H),
.24 (t, J＝6.7 Hz, 4H), 1.80－1.77 (m, 4H); C NMR
100 MHz, CDCl ) δ: 136.1, 132.3, 129.0, 127.6, 47.9,
further screened. Under the same anion (I ), the effect of
[3a]
1
cations on the electrolysis is negligible (Table 1, Entries
－9). In addition, further investigation on electrode
materials demonstrated that Cu (stainless steel or Ag) as
the cathode was also suitable for this electrolytic system
Table 1, Entries 10－12). According to our experi-
1
3
7
1
3
3
(
2
3
5.2.
(
mental results, the optimized electrolytic conditions
were obtained, as shown in Table 1 (Entry 4).
When the electrolysis was carried out on a 5 mmol
scale, the target product was obtained in 90% yield
Results and Discussion
With morpholine (1a) and sodium p-methylbenzene-
sulfinate (2a) as model substrates, electrolytic parame-
ters (solvents, supporting electrolytes and electrode ma-
terials) were examined. As shown in Table 1, when NaI
was used as the supporting electrolyte, the target prod-
uct arylsulfonamide 3aa could be obtained with high to
excellent yields in DMSO, DMF and DMA solvents
(
Scheme 2). In addition, the electrolyte solution could
be reused up to 10 times without an obvious reduction
in the yields. In the present system, NaI could be re-
peatedly used so that this electrochemical route could
greatly lower the synthetic cost and effectively avoid
generation of waste aqueous solution. Compared with
[
3,4a]
(
Table 1, Entries 1－3). Especially in the H O solvent
2
the previous reported synthetic routes
and our pre-
[4b]
case, the yield of 3aa could reach 94% (Table 1, Entry
). When NaI was replaced by NaCl or NaBr, the elec-
trolytic results obviously became poor (Table 1, Entries
and 6). This indicates that the anion of supporting
vious work, the present electrochemical route seems
to be greener and have more practial value.
4
5
Scheme 2 Electrolysis on a 5 mmol scale under the standard
electrolytes has a great effect on this transformation. In
the present electrochemical synthesis, supporting elec-
trolytes could not only serve as a conducting salt but
also participate in electrochemical reactions to generate
conditions

reactive species. For example, I anions are electro-

oxidized to form I at a graphite anode (i.e., 2I →I ＋
2
2

2
e ). I could promote the conversion of sodium sul-
fonates with amines to sulfonamides. So the property
of halogen anions could affect the electrolytic results
2
[
4]
Under the optimized reaction conditions, we first
studied the scope of the reaction with respect to amines.
As shown in Table 2, the present electrochemical route
could be applicable to a wide scope of amines, including
(
Table 1, Entries 4－6). Different iodides (NH I,
4
n-Bu NI and KI) as the supporting electrolytes were
4
Chin. J. Chem. 2016, XX, 1—6
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
3

Zhang et al.
FULL PAPER
aromatic (primary and secondary) amines, aliphatic
process may undergo a radical pathway. When
(
primary, secondary, cyclic and linear) amines and phe-
4 4
n-Bu NBF instead of NaI was used as the supporting
nylmethanamines. The corresponding target product
sulfonamides could be obtained in good to excellent
yields. Substitutional groups and molecular structures of
amines have an effect on the electrolytic results. Gener-
ally, the amines with electron-donating groups gave
better yields than those with electron-withdrawing
electrolyte, the target product 3aa could also be ob-
tained in 17% yield under the standard conditions
(Scheme 3b). This means that the electrochemical oxi-
dation of sulfinate anions to sulfonyl radical could also
occur at a graphite anode. In the absence of NaI, the
yield of 3aa is greatly lowered, which indirectly indi-

groups (such as 3d
pared with anilines (3e
are more suitable to this process (3d
phatic primary amines, the yield of the corresponding
product reduced with the increase of carbon chain (3f
3f a). In addition, the present route could tolerate
some functional groups such as －OH and halogen
3ba, 3d a and 3e a).
To demonstrate the efficiency and generality of this
2
a and 3d
3
a, 3e
a), phenylmethanamines
a－3d a). For ali-
2
a and 3e
3
a). Com-
cates that the electro-oxidation of I ions to I
2
plays a
1
a－3e
3
key role in this transformation. Under non-electro-
chemical conditions, the reaction of sodium sulfinate 2a
1
3
with I
amine (1a) does not react with I
morpholine (Scheme 3c). In addition, freshly prepared
2
could generate p-toluenesulfonyl iodide, while
1
a
2
to form N-iodo-
－
5
[8]
p-toluenesulfonyl iodide could react smoothly with
morpholine (1a) to afford the target product sulfona-
mide in an excellent yield at room temperature (Scheme
3d). Therefore, we deduce that the formation of sul-
fonamides may involve sulfonyl iodide intermediate
instead of N-iodoamine.
(
3
3
process, we further examined the scope of sodium sul-
finates (Table 3). It could be seen that sodium benzene-
sulfinate or its derivatives could well react with amine
to give the desired products in good to excellent yields
Based on our experimental results and the previous
researches, plausible mechanism is proposed in Scheme
4. The formation of sulfonamides may undergo two
(3ab－3ae). Unfortunately, the electrolysis with sodium
trifluoromethanesulfinate did not afford the desired
product (3af) due to very strong effect of the electron-
–
processes (path A and path B). On the one hand, I ani-
withdrawing group －CF
3
.
2
ons are first electro-oxidized to I at a graphite anode,
To understand this reaction mechanism, control ex-
periments were performed. In the presence of the radical
scavenger 1,1-diphenylethylene (Scheme 3a), the for-
mation of 3aa was suppressed dramatically and
by-product 4a was obtained, indicating that the reaction
followed by the reaction with sodium sulfinate to pro-
duce sulfonyl iodide intermediate, which is easily de-
composed to give a sulfonyl radical A1 and an iodine
radical (I ). Then, the amine reacts with the iodine
radical to yield amine radical A2, which subsequently
•
[9]
a
Table 2 Scope of amines
O
S
R1
O
H O-NaI, r.t.
H
N
2
N
+
S
R1
R2
R2
ONa
electrolysis
O
1
2
3
O
S
O
O
S
O
S
OH
O
N
S
N
N
N
O
H
H
O
O
O
O
3
aa, 90%
3ba, 90%
3ca, 80%
3d a, 91%
1
O
O
O
O
S
N
S
N
CI
S
NH
S
NH
H
H
O
O
O
O
d2a, 97%
3d3a
, 84%
3
3e a, 85%
3e a,90%
2
1
O
S
O
S
O
O
NH
Br
NH
S
N
S
N
H
H
O
O
O
O
3
e3a, 78%
3f a, 93%
1
3f a, 90%
3f a, 86%
2
3
O
H
O
O
O
S
N
S
N
S
N
S
N
H
O
O
O
O
3
f4a, 85%
3f5a, 80%
3
ga, 83%
3ha, 92%
a
Electrolytic conditions as shown in Table 1 (Entry 4). Isolated yield.
4
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Chin. J. Chem. 2016, XX, 1—6

Electrosynthesis of Arylsulfonamides from Amines and Sodium Sulfinates
Table 3 Scope of sodium sulfinates
a
a
Electrolytic conditions as shown in Table 1 (Entry 4). Isolated yield.
Scheme 3 Control experiments
Ph
O
S
O
S
Ph
standard conditions
N
O
2
a
+
1
a
+
1
,1-diphenylethylene
O
O
(
1 equiv.)
3
aa, 54%
4a, 30%
O
O
S
ONa
n-Bu NBF - H O
4
4
2
S
N
O
O
NH
+
electrolysis
O
1
a
a
2a
3
aa, 17%
H O, r.t.
2
O
NH
I2
+
O
N
I
+
HI
non-electrolysis
1
0
%
O
O
H O, r.t.
2
S
I
+
O
NH
S
N
O
non-electrolysis
O
O
1
a
3
aa, 90%
Scheme 4 Plausible reaction mechanism
Cathode
Anode
Path A (main)
R1
N
O
S
R1
R2
A2
-HI
R2
R
N
R1
NH
O
R2
O
O
O
R
S
ONa
-
2e
-
-
R
S
I
I2
I
2I
R
S
O
+
O
NaI
A1
R1
2
H O
2
NH
R2
-
+
2e
O
S
-
O
-
2e
H + 2OH-
H+
R
OH
O-
2
+
R
S
+
2
H O
O
A3
Path B (minor)
Chin. J. Chem. 2016, XX, 1—6
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5

Zhang et al.
FULL PAPER
Scheme 5 A total reaction equation for this transformation
reacts with the sulfonyl radical A1 to form the target
product (path A). In addition, the direct reaction of the
sulfonyl iodide with the amine could produce the target
Bhattacharyya, B. J. Med. Chem. 2005, 48, 547; (b) Pandya, R.;
Murashima, T.; Tedeschi, L.; Barrett, A. G. M. J. Org. Chem. 2003,
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8, 8274; (c) Natarajan, A.; Guo, Y.; Harbinski, F.; Fan, Y.-H.; Chen,
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004, 47, 4979; (d) Gilbert, A. M.; Caltabiano, S.; Koehn, F. E.;
2
product. On the other hand, sulfinate anions with H O
2
could also be electro-oxidized to generate a sulfonic
acid A3 at the anode (path B, minor process). Then, the
sulfonic acid A3 easily reacts with amine to give the
Chen, Z.; Francisco, G. D.; Ellingboe, J. W.; Kharode, Y.; Mangine,
A. M.; Francis, R.; TrailSmith, M.; Gralnick, D. J. Med. Chem. 2002,
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target product sulfonamide. At the same time, H
2
O sol-

vent is electro-reduced to generate H
2
and OH anion. A
[
total reaction equation for this transformation is shown
in Scheme 5. According to the experimental results (Ta-
ble 1, Entry 4 and Scheme 3b), it could be concluded
1
775; (c) Bahrami, K.; Khodaei, M. M.; Soheilizad, M. J. Org.

that the electrochemical oxidation of I anions to I
key step. It is noteworthy that I anions are able to recy-
cle during the electrolysis. In fact, the formation of sul-
2
is a
Chem. 2009, 74, 9287; (d) Shi, F.; Tse, M. K.; Cui, X. J.; Gördes, D.;
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–
7
5, 2726; (f) Rosen, B. R.; Ruble, J. C.; Beauchamp, T. J.; Navarro,
fonamides only consumes electrons and H
2
O solvent
A. Org. Lett. 2011, 13, 2564; (g) Lakrout, S.; K’tir, H.; Amria, A.;
Berredjem, M.; Aouf, N. E. RSC Adv. 2014, 4, 16027; (h) Huang, X.;
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besides the substrates. In order to reuse the NaI-H
2
O
2 4
electrolyte solution, extra acid (such as H SO ) is need-
ed to neutralize the base electrogenerated.
Conclusion
2
011, 76, 4552.
In conclusion, a green and efficient electrochemical
method has been developed for the synthesis of aryl-
[
[
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2
to promote reaction of sodium sulfinates with amines at
room temperature. In the present electrochemical sys-
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1
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Green Chem. 2015, 17, 1400.
sulfonamides only consumes electrons and H O solvent
2
[
[
5] Yu, H.; Zhong, Y. H. Chin. J. Chem. 2016, 34, 359.
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chemical route features its environmental friendliness,
simplicity, low-cost and easily scalable production,
showing its potential application for the synthesis of
arylsulfonamides.
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Acknowledgments
[
[
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This work was financially supported by the National
Natural Science Foundation of China (Nos. 21572070
and 21172079).
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© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—6