Ammonium iodide-mediated electrosynthesis of unsymmetrical thiosulfonates from arenesulfonohydrazides and thiols

Article abstract of DOI:10.1016/j.mencom.2019.01.027

Unsymmetrical thiosulfonates were synthesized from thiols and arenesulfonohydrazides by their electrolysis in undivided cell equipped with graphite anode and stainless steel cathode under high current density applying NH₄I both as a redox catal

Full text of DOI:10.1016/j.mencom.2019.01.027

Mendeleev
Communications
Mendeleev Commun., 2019, 29, 80–82
Ammonium iodide-mediated electrosynthesis of unsymmetrical
thiosulfonates from arenesulfonohydrazides and thiols
Alexander O. Terent’ev,*a,b Olga M. Mulina,a Alexey I. Ilovaisky,a
Vladimir A. Kokorekina,c 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 I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russian Federation
DOI: 10.1016/j.mencom.2019.01.027
Unsymmetrical thiosulfonates were synthesized from thiols
and arenesulfonohydrazides by their electrolysis in undivided
cell equipped with graphite anode and stainless steel cathode
under high current density applying NH4I both as a redox
catalyst and a supporting electrolyte. In the course of the
process, oxidative formation of S–S bond occurs with the loss
of hydrazine moiety.
O
S
O
S
Electrolysis
R
+
NHNH2
Ar
RSH
Ar
S
NH4I
THF–H2O
O
O
Yields up to 80%
13 examples
The reactions of sulfonyl chlorides with thiols leading to thio-
sulfonates1 suffer from low selectivity due to the rapid formation
of disulfides as a result of nucleophilic substitution of sulfo group
in thiosulfonates by the action of thiols. Oxidative methods2
represent a good alternative for this approach. Thiosulfonates
have been successfully synthesized by reactions between sodium
sulfinates/sulfonyl hydazides and thiols/disulfides using various
oxidative systems3–9 or through disproportionation of sodium
sulfinates.10
The application of electric current in organic synthesis is
attractive due to its low price and environment-friendliness.11
In this context, we report on electrosynthesis of thiosulfonates
by means of electrochemical oxidative formation of S–S bond.
This transformation runs fast in undivided electrochemical cell
with the use of graphite anode and iron cathode, and is tolerant
to both electron-donating and electron-withdrawing groups in
starting compounds.12
The co-electrolysis of arenesulfonohydrazides 1a–i and thiols
2a–e was studied in H2O–THF, H2O–dioxane, EtOH–THF, EtOH
or DMSO solution with KI, NH4I, NBu4I, NH4Br and NH4Cl
as supporting electrolytes in undivided cell at constant current
(50 mA cm–2) (Scheme 1). The choice of solvents is based on
their high electric conductivity and low reactivity under these
conditions. Halogen-containing supporting electrolytes permit
formation of molecular halogens which can oxidize the starting
hydrazides 1. Current density and reaction temperature values
were chosen for conducting the electrosynthesis fast enough and
avoiding formation of significant quantities of side products. As
a result, thiosulfonates 3a–m were obtained (see Scheme 1).
p-Toluenesulfonohydrazide 1a and thiophenol 2a were selected
as model reactants for the estimation of optimal conditions for
the electrosynthesis of thiosulfonate 3a (Table 1).
For the full conversion of 1a and 2a into 3a, four electrons are
theoretically needed. Initially we decided to conduct experiments
applying slight excess of electricity passed (5 F per mole of 1a).
In entries with non-equal amounts of reactants, the yield of
compound 3a and amount of electricity passed were calculated
relative to the reactant taken in less amount for more convenient
comparison of the experiment results. In entries 1–5, the nature
of supporting electrolyte was shown to be crucial for the reaction
outcome. Only in the cases of KI and NH4I, the target product 3a
was formed in detectable amounts (entries 1, 2), however NH4I
provided its better yield (entry 2). Entries 6–8 demonstrate that
the use of 1 mol of NH4I per 1 mol of hydrazide 1a is optimal.
Conducting the process with the excess of any of the reactants led
to a significant increase of 3a yield up to 57–70% (entries 9–13).
Application of 2 mol of 2a per 1 mol of 1a turned out to be the
most appropriate (entry 12). Raising the electric charge passed to
10 F mol–1 (entry 14) did not improve the yield of product 3a
and further increase in this value to 15 F mol–1 dropped the yield
to 40% (entry 15). Decreasing of electricity passed to theoretical
O
O
O
Electrolysis
RSH
+
Ar
S
NHNH2
S
R
Ar
S
O
1a–i
2a–e
3a–m
Reactants Product Yield (%)
1a Ar = 4-MeC6H4
1b Ar = 4-MeOC6H4
1c Ar = 4-FC6H4
1d Ar = 4-ClC6H4
1e Ar = 4-BrC6H4
1f Ar = 4-IC6H4
1g Ar = 4-O2NC6H4
1h Ar = 2-naphthyl
1i Ar = 2,4,6-Me3C6H2
1a + 2a
1b + 2a
1c + 2a
1d + 2a
3a
3b
3c
3d
3e
3f
3g
3h
3i
70
61
55
46
66
57
25
43
30
68
80
35
55
+
1e 2a
+
1f 2a
+
1g 2a
+
1h 2a
+
2a R = Ph
1i 2a
+
1a 2b
2b R = 4-MeC6H4
2c R = 4-ClC6H4
2d R = Bui
3j
3k
3l
+
1a 2c
+
1a 2d
+
1a 2e
2e R = Bu
3m
Scheme 1 Reagents and conditions: sulfonohydrazide 1 (1 mmol), thiol 2a
(2 mmol) and supporting electrolyte NH4I (1 mmol) in H2O–THF (30 ml,
1:1) was electrolyzed at constant current (50 mA cm–2) at 30°C.
© 2019 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 80 –

Mendeleev Commun., 2019, 29, 80–82
Table 1 Optimization of the reaction conditions for the synthesis of thio-
sulfonate 3a from p-toluenesulfonohydrazide 1a and thiophenol 2a.a
thiosulfonates 3g and 3i formed in low yields (the reduction of
nitro group on the cathode and bulkiness of mesitylene moiety).
Arenethiols 2b,c and alkanethiols 2d,e also successfully enter
into this reaction affording thiosulfonates 3j–m in yields from
moderate to high.
Molar
Entry ratio
Supporting
electrolyte
(mmol)
Electricity
passedb /
F mol–1
Yield of
Solvent
3a (%)c
1a:2a
In a multigram electrosynthesis (10 mmol of hydrazide 1a
and 20 mmol of thiophenol 2a) under the optimized conditions
(see Table 1, entry 12) product 3a was isolated in 64% yield.
Cyclic voltammetry (CV) experiments were run to get insight
into the reaction mechanism. For this purpose, working glassy-
carbon electrode, H2O–THF (1 : 1) solvent, and tetrabutyl-
ammonium perchlorate as a non-oxidizable supporting electrolyte
were chosen. The redox properties of p-toluenesulfonohydrazide
1a, thiophenol 2a and NH4I in H2O–THF (1:1) solution were
studied. Obtained CV curves are shown in Figure 1. Iodide-anion
oxidation occurs at the earliest potentials as +0.55 V. Chemically
irreversible oxidation of p-toluenesulfonohydrazide 1a proceeds
at +1.18 V. Thiophenol 2a is oxidized most difficultly at +1.52 V.
According to obtained data, one may conclude that under experi-
mental conditions NH4I serves both as a supporting electrolyte
and a redox catalyst.
On the basis of literature and experimental data we proposed
a mechanism for the process in question (Scheme 2). At the first
reaction step, iodide anion is oxidized on the anode to molecular
iodine,13 which further oxidizes arenesulfonohydrazide 1 resulting
in the generation of arenesulfonyl iodide A.14 Hypoiodites, iodates
or periodates can also be involved in the processes of iodide-
anion oxidation and formation of arenesulfonyl iodide A.15 They
are mainly produced as a result of the reaction between molecular
iodine and hydroxide anion formed by the cathodic reduction
of H2O.16 The thiosulfonate 3 can be formed from A through
several different ways. The first one is nucleophilic attack of
thiol 2 on the iodide A with the elimination of HI. Thiol 2 can
1
2
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1.5:1
2:1
3:1
1:2
1:3
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
KI (3)
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–THF
H2O–dioxane
EtOH–THF
EtOH
5
5
17
NH4I (3)
NBu4I (3)
NH4Br (3)
NH4Cl (3)
NH4I (2)
NH4I (1)
NH4I (0.5)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
NH4I (1)
LiClO4 (1)
43
3
5
trace
<10
<10
49
4
5
5
5
6
5
7
5
51
8
5
34
9
5
57
10
11
12
13
14
15
16
17
18
19
20
21
5
62
5
67
70 (68d)
5
5
68
10
15
4
65
40
24
5
47
5
57
5
22
DMSO
5
trace
14
H2O–THF
5
a General procedure: a solution of p-toluenesulfonohydrazide 1a (1–3 mmol),
thiophenol 2a (1–3 mmol) and supporting electrolyte (0.5–3 mmol) in
H2O–THF (1:1), H2O–dioxane (1:1), EtOH–THF (1:1), EtOH or DMSO
(30 ml) was electrolyzed at constant current (50 mA cm–2) at 30 °C under
magnetic stirring with the use of graphite anode and stainless steel cathode.
b In entries 1–8 and 12–21 the electricity passed was calculated relative to
1a, in entries 9–11 relative to 2a. c Isolated yield based on reactant taken
in less amount. d Electrolysis with platinum electrodes.
O
S
O
S
O
S
I2, [I]+
value (4 F mol–1) caused the dramatic fall in the yield (entry 16).
Replacement of H2O–THF system with other solvents resulted
only in decrease of 3a yield (entries 17–20). Change of electrode
material (entry 12, in parentheses) gave compatible result. When
inert electrolyte LiClO4 (entry 21) was tested, the yield of 3a was
as low as 14%. This fact proved our initial proposal concerning
the participation of generated from NH4I molecular iodine in
sulfonohydrazide oxidation. The side reaction was the formation
of diphenyl disulfide, which was a real obstacle to achieve higher
yields of the target product. Therefore, the optimal conditions
were as follows: 1 mol of NH4I, 2 mol of thiol 2a per 1 mol
of sulfonohydrazide, H2O–THF (1:1) as the solvent, 5 F mol–1 of
electricity passed (see Table 1, entry 12).
Ar
NHNH2
Ar
I
Ar
– I
O
O
A
O
1
B
H2 + OH–
2 I–
I
I2
B + D
H2O
OH–
O
O
I+
S
Ar
SR
I–
I2, [I]+
3
HI
S
R
R
S
A
E
A
R
S–
R
SH
2
or C
With optimized conditions in hand, we tested a wide range of
arenesulfonohydrazides 1a–i and thiols 2a–e in order to explore
the scope of the procedure (see Scheme 1). The target thio-
sulfonates 3 were generally obtained in yields from moderate to
high, but in the cases of compounds 1g and 1i the corresponding
C
2
I2, [I]+
R
SI
OH–
D
Scheme 2
(c) 0.25
(a) 0.04
0.03
(b) 0.07
0.06
1.18 V
0.55 V
1.52 V
0.20
0.15
0.10
0.05
0.0
0.05
0.02
0.04
0.03
0.02
0.01
0.00
–0.01
0.01
0.00
–0.01
–0.4 –0.2 0.0 0.2 0.4 0.6
–0.4
0.0
0.4
0.8
1.2
–0.3 0.0 0.3 0.6 0.9 1.2 1.5
E/V (vs. SCE)
E/V (vs. SCE)
E/V (vs. SCE)
Figure 1 The CV curves obtained for 3.0 mm solutions of (a) NH4I, (b) p-toluenesulfonohydrazide 1a and (c) thiophenol 2a in H2O–THF (1:1), containing
Bu4NClO4 (0.1 mol dm–3), on a working glassy-carbon electrode (d = 1.7 mm) at a scan rate of 100 mV s–1.
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Mendeleev Commun., 2019, 29, 80–82
10 L. Cao, S.-H. Luo, K. Jiang, Z.-F. Hao, B.-W. Wang, C.-M. Pang and
also be deprotonated with hydroxide anion formed on the cathode
to give thiolate anion C, which can react with sulfonyl iodide A
providing desired product 3. Thiolate anion C can be oxidized
with molecular iodine11(c) or hypoiodites, iodates, periodates,
providing sulfenyl iodide D.17 Its reaction with sulfonyl radical
B18 generated from unstable sulfonyl iodide A also results in
thiosulfonate 3.19 Side disulfide E can be produced as a result
of the reaction of thiol 220 or thiolate anion C with sulfenyl iodide
D,21 as well as oxidation of thiolate anion C with molecular iodine,
hypoiodites, iodates and periodates followed by recombination
of formed thiyl radicals.22 In addition, thiyl radical and thiolate
anion C can be generated through the reductive cleavage of S–S
bond in diorganyl disulfide E.
To summarize, we have demonstrated application of electric
current for the synthesis of unsymmetrical thiosulfonates from
arenesulfonohydrazides and thiols through oxidative S–S bond
formation. The process is conducted in an undivided electro-
chemical cell equipped with graphite anode and stainless steel
cathode. Ammonium iodide was applied both as a supporting
electrolyte and a redox catalyst. A wide scope of starting com-
pounds successfully enters into this reaction. A possible reaction
mechanism was proposed with the use of cyclic voltammetry.
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This work was supported by the Russian Foundation for Basic
Research (grant no. 18-33-00693).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2019.01.027.
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Received: 2nd October 2018; Com. 18/5702
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