Electrochemical synthesis of sulfonamides from arenesulfonohydrazides or sodium p-methylbenzenesulfinate and amines

Article abstract of DOI:10.1016/j.mencom.2016.11.027

An efficient electrochemical synthesis of sulfonamides (yields 56–98%) from arenesulfonohydrazides or sodium p-methylbenzenesulfinate and amines was performed in an undivided cell with graphite anode and iron cathode in MeCN–H₂O medium using halides as redox mediators and supporting electrolytes.

Full text of DOI:10.1016/j.mencom.2016.11.027

Mendeleev
Communications
Mendeleev Commun., 2016, 26, 538–539
Electrochemical synthesis of sulfonamides from arenesulfonohydrazides
or sodium p-methylbenzenesulfinate and amines
Alexander O. Terent’ev,*a,b,c Olga M. Mulina,a Dmitry A. Pirgach,a,b Mikhail A. Syroeshkin,a
Alexey P. Glinushkinc and Gennady I. Nikishina
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5328; e-mail: terentev@ioc.ac.ru
b D. I. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russian Federation
c All-Russian Research Institute for Phytopathology, 143050 B. Vyazyomy, Moscow Region, Russian Federation
DOI: 10.1016/j.mencom.2016.11.027
O
An efficient electrochemical synthesis of sulfonamides
O
S
R2
NHNH2
(yields 56–98%) from arenesulfonohydrazides or sodium
p-methylbenzenesulfinate and amines was performed in an
undivided cell with graphite anode and iron cathode in
MeCN–H2O medium using halides as redox mediators and
supporting electrolytes.
S
O
N
R1
Constant current
O
R1
R2
R
+
MeCN–H2O
KI, NaI, NH4I,
KBr, NaBr, NH4Br
or
N
R
H
SO2Na
56–98%
14 examples
Me
Sulfonamides play an important role in the modern organic1 and
medicinal chemistry.2,3 Sulfonamide moiety is widespread in
natural and biologically active compounds.4 Substances of this
class possess antibacterial,5,6 anticancer,7,8 antiviral,9 anticonvul-
sant,10 anti-inflammatory,11 and anti HIV protease activity.12
Traditionally sulfonamides are prepared by the reactions of
sulfonyl chlorides with amines,13–15 N-coupling of N-unsub-
stituted sulfonamides with alcohols,16–18 organic halides,19–21
arylboronic acids22,23 and by transition metal catalyzed sulfo-
nylation of hydrocarbons.24,25 In the past years, transformations
of sulfonyl azides26,27 and oxidative S–N coupling28–30 of arene-
sulfonohydrazides and sodium arylsulfinates using CuBr2 and
I2/TBHP and TBAI/TBHP systems were documented.
Redox processes with organic compounds are widely imple-
mented using electrochemical techniques31,32 by the following
reasons: availability and low cost of electric current, variety of
electrochemical reaction mechanisms and decrease in waste
amounts.33 The main idea of our work was the replacement of
chemical oxidants applied for oxidative S–N coupling of arene-
sulfonohydrazides and sodium arylsulfinates with amines by
anodic oxidation.
Electrolysis of arenesulfonohydrazides 1a–f and amines 2a–i
at constant current density 35–40 mA cm–2 in an undivided
cell with graphite anode and iron cathode affords the target
sulfonamides 3 (Scheme 1).
Optimal reaction conditions were selected on the example of
the synthesis of p-toluenesulfonomorpholide 3aa from reactants
1a and 2a (Table 1).
O
S
NHNH2
R1
R2
+
N
O
H
R
1a R = Me
1b R = OMe
1c R = I
2a R1 + R2 = (CH2CH2)2O
2b R1 + R2 = (CH2)5
Entries 1, 2 (see Table 1) show that the complete conversion of
compound 1a was achieved on passing 5 F mol–1 electricity.
2c R1 + R2 = (CH2CH2)2CHCOOEt
2d R1 + R2 = (CH2)4
1d
1e
1f
R = Br
R = Cl
R = NO2
2e R1 + R2 = (CH2)6
Table 1 Electrochemicalsynthesisofsulfonamide3aafromp-toluenesulfono-
hydrazide 1a and morpholine 2a.a
2f R1 = R2 = Me
R1 = R2 = Et
2g
2h
2i
Molar ratio Supporting
Electricity passed/ Isolated yield
R1 = H, R2 = Me
Entry
1a:2a
electrolite
F per mole of 1a
of 3aa (%)
R1 = H, R2 = Bn
1
1:2
KI
3
5
5
5
5
5
5
5
5
5
5
62
85
79
85
75
92
90
91
93
95
96
O
R2
2
1:2
KI
S
N
R1
3
1:3
KI
O
4
1:1.5
1:1
KI
R
5
KI
3aa (95%) 3af (90%) 3ca (92%)
6
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
NaI
3ab (93%)
3ac (98%)
3ad (94%)
3ae (90%)
3da (95%)
3ag (63%)
7
NH4I
KBr
NaBr
NH4Br
NH4Cl
3ah (90%) 3ea (76%)
3ai (56%) 3fa (73%)
3ba (91%)
8
9
10
11
Scheme 1 Reagents and conditions: molar ratio 1:2 was 1:1.5, NH4Br in
MeCN–H2O, constant current, Fe cathode, graphite anode, 25–30 °C. In the
designations of products 3 the first letter shows arenesulfonohydrazide 1
moiety, the second is amine 2 moiety. Isolated yields are given. For 3ag:
KBr was used. For 3ah and 3ai: molar ratios 1:2 were 1:3.
aThe solution of 1a (300 mg, 1.61 mmol), 2a (1.61–4.83 mmol) and electrolyte
(0.8 mmol, 0.5 equiv. with respect to 1a) in 30 ml of MeCN–H2O (1:1) was
electrolyzed at 25–30 °C under magnetic stirring.
© 2016 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 538 –

Mendeleev Commun., 2016, 26, 538–539
Optimal molar excess of morpholine 2a above 1a is 1.5 (entry 4),
cell with graphite anode and iron cathode was developed. An
advantage of this electrochemical process is the possibility of
using high current density (35–40 mA cm–2), which permits to
carry out the synthesis fast and employ small electrodes surface
(6–7 cm2).
providing 85% yield of 3aa (cf. entries 3–5). Sulfonamide 3aa
was obtained in high yields using a wide range of supporting
electrolytes: KI, NaI, NH4I, KBr, NaBr, NH4Br, and NH4Cl
(entries 4, 6–11), however the best results were achieved with
NH4Br and NH4Cl (entries 10, 11). Mainly under optimized
conditions of entry 10 compounds 3aa–3fa were synthesized in
56 to 98% yields (see Scheme 1).†
This work was supported by the Russian Science Foundation
(grant no. 14-23-00150).
In general, yields of sulfonamides 3aa–3fa did not depend
crucially on the nature of sulfonohydrazide 1 and amine 2. The
main condition for successful reaction using primary amines 2h
and 2i was the use of threefold excess of amine 2. Influence of
the electron-withdrawing group in p-chloro- and p-nitro-sub-
strates 1e and 1f is probably the reason of lower yields of the
corresponding sulfonamides 3ea and 3fa. On using anilines as
N-reagents, the formation of N-arylated sulfonamides was not
observed.
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2016.11.027.
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O
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In conclusion, effective and selective electrochemical synthesis
of sulfonamides (yields 56–98%) from arenesulfonohydrazides
or sodium p-methylbenzenesulfinate and amines in an undivided
†
General procedure. An undivided cell was equipped with a carbon plate
anode (7.5 cm2) and a Fe plate cathode (7.5 cm2) and connected to a DC
regulated power supply. The solution of corresponding amine 2 (1.5–
4.83 mmol) in 30 ml MeCN–H2O (1:1), arenesulfonohydrazide 1 (300 mg,
1.00–1.61 mmol) and supporting electrolyte KBr, NH4Br (0.5–0.8 mmol;
molar ratio to 1 was 1:2) were added to the cell. The mixture was
electrolyzed with constant current (35–40 mA cm–2) at 25–30 °C under
magnetic stirring. Then the solvent was removed under reduced pressure
(10–20 Torr). The residue was diluted with EtOAc (50 ml) and washed
with brine (2 × 8 ml) and water (2 × 8 ml), dried over Na2SO4, and
concentrated under reduced pressure (10–20 Torr). Then it was purified by
recrystallization from ethanol.
Received: 25th May 2016; Com. 16/4943
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