recovered (99%) (Scheme 2 D). Therefore, the oxidation of
disulfide to thiosulfonate pathway was able to be ruled out.8f
Quantum chemical simulations were carried out using 1c as a
model substrate to investigate the Cu-promoted decomposition of
sulfonyl hydrazides into A. It was predicted that the Cu-promoted
decomposition of 1c is thermodynamically viable with the
accessible reaction barrier of 28.1 kcal/mol. However, this result
does not necessarily exclude the other possible mechanisms such
as Brønsted acid promoted or thermally activated decomposition
of sulfonyl hydrazide.
Me
O
S
O
O O
CuCl2 (10 mol %)
NH2
S
N
S
toluene, N2
90 oC, 15 h
H
Me
Me
1a
1.8 g (10 mmol)
2a
1.3 g (94%)
Scheme 1. Scale up process for Cu-promoted decomposition
In summary, we have achieved the selective transformation of
sulfonyl hydrazides into thiosulfonates using catalytic amounts of
CuCl2. The use of stoichiometric oxidants such as O2 or K2S2O8
was not required in the developed protocol. Compared to the
thermal decomposition of sulfonyl hydrazides, the reaction rate
of the developed protocol was much faster. Both benzenesulfonyl
hydrazides having either electron-withdrawing or electron-
donating groups and aliphatic sulfonyl hydrazides efficiently
underwent the present protocol to produce the corresponding
thiosulfonates. From the mechanistic experiments and related
references, it was proposed that the reaction of sulfonyl radical
with thiyl radical or disulfide produced the desired thiosulfonates.
The computational simulation suggested that the Cu-promoted
decomposition of sulfonyl hydrazides is thermodynamically
viable.
of sulfonyl hydrazide for thiosulfonate.
(A)
O
S
O
O
S
O
CuCl2 (10 mol %)
NH2
Tol
Tol
N
Tol
S
toluene, N2
90 oC, 15 h
H
1a
2a
, 10%
optimized conditions
with TEMPO (1.0 equiv)
Tol =
Me
optimized
conditions
(B)
O
O
O
S
O
S
Ph
S
Tol
Ph
+
1a
+
S
Ph
Tol
2a
S
Tol
S
3
0.5 mmol
(0.5 mmol)
, 18%
(0.045 mmol)
4
, 37%
(0.19 mmol)
optimized
conditions
(C)
O
O
S
S
Ph
Ph
S
2a
Ph
+
Tol
S
3
4
, 0%
optimized
conditions
(D)
O
O
S
Ph
Acknowledgments
S
Ph
S
Ph
Ph
S
3
2c
, 0%
This work was supported by the Incheon National University
Research Grant in 2018.
Scheme 2. Control experiments for mechanistic investigation.
On the basis of our observations and related references, a
plausible proposed mechanism with 1c was depicted in Scheme 3.
At first, one sulfonyl hydrazide undergoes Cu(II)-promoted
oxidative decomposition to produce a sulfonyl radical with Cu(I)
(Scheme 3 A).16 It is suggested the other sulfonyl hydrazide
might undergo a couple of decompositions for the generation of
sulfenyl compound B and the reduction of B with Cu(I) generates
the crucial intermediate, thiyl radical, with releasing nitrogen gas
(Scheme 3 B).8a,8h,17 The production of disulfide as a side product
would be attributed to dimerization of the generated thiyl radical.
Finally, the reaction between sulfonyl radical and thiyl radical
produces the desired thiosulfonate (Scheme 3 C). In some case,
the thiosulfonate is able to be produced by the reaction of the
sulfonyl radical with disulfide, according to the observation in
Scheme 2 C. However, other mechanisms involving the
generation of sulfinyl radical from A can not totally ruled out at
this stage due to the complicate decompositions of sulfonyl
hydrazides.18
Supplementary Material
Supplementary data (experimental procedures for sulfonamide
synthesis, and 1H and 13C NMR spectra of the products)
associated with this article can be found, in the online version, at
References and notes
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(A)
Cu(II)
Cu(I)
Ph
O
S
O
S
H
Ph
N NH2
O
O
1c
(B)
O
1c
Ph
S
N NH
A
6.
7.
For reviews, see: (a) F.-L. Yang, S.-K. Tian, Tetrahedron Lett.
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A
B
Ph
S
N N
B
Cu(I)
Cu(II)
Ph
S S Ph
Ph
S
(C)
Ph
S
O
S
O
+
Ph
or
Ph
S
S Ph
O
O
Ph
S S Ph
8.
For selected examples, see: (a) F.-L. Yang, S.-K. Tian, Angew.
Chem. Int. Ed. 2013, 52, 4929; Angew. Chem. 2013, 125, 5029;
(b) X. Li, Y. Xu, W. Wu, C. Jiang, C. Qi, H. Jiang, Chem. Eur. J.
Scheme 3. Proposed mechanism.