Symmetrical disulfide synthesis via nickel-catalysis using potassium sulfide as sulfur source
with 2-iodothiophene in good yield (Table 3, entries 8–10).
Table 2 Screening of the S-source
However, reactions were not complete after 24 h in the
presence of electron-donating groups such as OMe and Me
(Table 3, entries 6 and 7). In the case of aryl halides with
base and acid sensitive groups such as amino (Table 3,
entry 14) and carboxyl (Table 3, entry 15) without the need
of a protecting group the corresponding disulfides were
obtained in 67 and 95 % yields, respectively (Table 3).
This protocol was also applied for the primary alkyl
halides and potassium sulfide in the optimal reaction con-
ditions. In the case of primary alkyl halides the desired
products were obtained in high yields when compared to
diaryl disulfides.
Entry
S source
Yield/%a
1
2
3
4
5
6
7
K2S
90
KSCN
30
Thiourea
Thioacetamide
S8
35
30
40
Na2S2O3
Na2S
No reaction
27
Reaction conditions: Ph-I (2.0 mmol), S source (3.0 mmol), NiCl2-
a
6H2O (10 mol%), KOH (18.0 mmol), 110 °C. Isolated yields
The mechanistic understanding of this protocol is not
established yet; however, a working hypothesis is shown in
Scheme 1. It seems, after coordination of Ni center with
acac, complex 3 was produced through oxidative addition
of Ar–X to Ni [35, 36]. Then, intermediate 4 was yielded
by nucleophilic substitution of potassium sulfide to com-
plex 3. Finally, aryl thiolate 5 is generated via elimination
from intermediate 4. Subsequently, ArSK 5 is transformed
to the corresponding diaryldisulfide under oxidative opti-
mal reaction conditions [37, 38].
Many solvents such as DMF, DMSO, polyethylene
glycol (PEG 400), EG, H2O, PhMe, EtOH, MeCN, NMP,
THF, and 1,4-dioxane were screened and the results are
summarized in Table 1 (entries 9–17). Furthermore, sev-
eral bases such as K2CO3, NaOH, Et3N, TBAOH, and
KOH were tested. KOH was the best performing base in
this study affording diphenyl disulfide in 90 % yield. The
effect of the reaction temperature on the progress of the
reaction also was investigated. With increasing tempera-
ture, the purity and yield of diphenyl disulfide were
increased (Table 1, entries 23–25). Subsequently, different
nickel salts (10 % mol) were examined. The best result was
obtained with NiCl2. In comparison to Ni(NO3)2, Ni(OAc)2
and Ni(SO4)2, NiCl2 gave the highest yield (see Table 1,
entries 3 and 26–28). Decreasing the catalyst loading to
5 mol% of NiCl2Á6H2O resulted in 54 % conversion.
Additionally, some commercially available and
stable organic and inorganic sulfur sources were studied in
the NiCl2-catalysed reaction with iodobenzene (model
reaction, Table 2). K2S was not only found more effective
than other commercial sulfur sources, but was also proven
to be better than synthetic sulfur sources such as mor-
pholin-4-ium morpholine-4-carbodithioate [32, 33] and
Conclusion
In conclusion, we have introduced an efficient and one-pot
Ni-catalyzed method for the synthesis of symmetrical
disulfides by the domino and direct cross coupling reaction
of aryl halides with potassium sulfide in DMF at normal
atmospheric reaction conditions with good to excellent
yield. The main features of this method are: (1) the use of
potassium sulfide as an inorganic sulfur-source, which is a
commercially available, inexpensive, and stable solid and
free of foul-smelling thiols; and (2) NiCl2Á6H2O
(10 mol%) was also used as a more reactive, cost effective,
safe, and readily available catalyst. Simple handling, easy
work-up, general applications, and normal atmospheric
conditions are other advantages of this protocol.
potassium
5-methyl-1,3,4-oxadiazole-2-thiolate
[34],
which are used in our previous works. The results are listed
in Table 2.
We then evaluated the scope of the cross coupling
reaction under optimized conditions. The reaction between
various aryl halides with different electronic properties and
potassium sulfide, using NiCl2Á6H2O in DMF at 110 °C
under normal atmospheric conditions, gave the expected
products. Many types of aryl and hetero aryl halides with
different functional groups were used. The results are
summarized in Table 3. Generally, the aryl halide deriva-
tives, bearing both electron-withdrawing and electron-
donating groups provide good to excellent yields. This
procedure was also examined to convert heteroaryl halides
such as 2-chlorothiophene, 2-bromothiophene, and
2-iodothiophene to the corresponding disulfides; it worked
Experimental
General procedure for the synthesis of diaryl
(dialkyl) disulfides
To a stirred mixture of aryl (primary alkyl) halide
(2.0 mmol), 0.33 g potassium sulfide (3.0 mmol) and acac
(20 mol%) in 2 cm3 DMF (containing a few drops water),
NiCl2Á6H2O (10 mol%) and then 1.0 g KOH (18.0 mmol)
were added and the whole reaction mixture was heated at
110 °C under atmospheric conditions until completion. The
123
Soleiman-Beigi, Mohammad
