Full text of DOI:10.1002/ejoc.201701056

A Journal of
Accepted Article
Title: Copper-catalyzed S-arylation of tetraalkylthiuram disulfides by
using diaryliodonium salts
Authors: Zhi-Bing Dong, Meng-Tian Zeng, Wan Xu, Xing Liu, Cai-Zhu
Chang, and Hui Zhu
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701056
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701056
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European Journal of Organic Chemistry
10.1002/ejoc.201701056
FULL PAPER
Copper-catalyzed S-arylation of tetraalkylthiuram disulfides by
using diaryliodonium salts
[
a]
[a]
[a]
[a]
[a]
[a], [b]
Meng-Tian Zeng, Wan Xu, Xing Liu, Cai-Zhu Chang, Hui Zhu, Zhi-Bing Dong*
Results and Discussion
Abstract: An efficient and convenient procedure for the S-arylation
In preliminary studies, diphenyliodonium triflate (1a) and
tetramethylthiuram disulfide (TMTD ， 2a) were selected as
substrate for model reaction under various conditions (Table 1).
For the first trial, we expected the reaction to proceed in green
solvents with no addition of metal and base, but phenyl
dithiocarbamate was obtained in low yields (25-30%, Table 1,
of tetraalkylthiuram disulfides by using diaryliodonium salts was
explored. In the presence of CuI/KOt-Bu, two kinds of S-aryl
dithiocarbamates could be obtained with good to excellent yields at
one time, showing no obvious selectivity. The methodology has
advantages of efficiency, good atomic economy and broad substrate
scope. The method provides a facile and convenient preparation of
some potentially biologically active compounds.
2 2 3
entries 1–4). We then added catalyst (CuCl ) and base (K CO )
to the aqueous solution, the yields were still poor (Table 1,
entries 5-6). To our delight, the target compound could be
furnished in a relatively higher yield (65%, Table 1, entry 7) in
the presence of CuI/K
2
CO
3
/DMF. Then, a range of bases, such
N and CH ONa were
Introduction
as K CO , CS CO , KOt-Bu, KOH, Et
2
3
2
3
3
3
surveyed and KOt-Bu was found to be the most suitable base for
this reaction (Table 1, entries 7-12). Subsequently, a broad
screening of copper, iron, nickel and palladium catalysts was
performed (Table 1, entries 13-20). It revealed that iron, nickel
and palladium salts were not (or less) effective, but copper
catalysts could catalyze the model reaction to give reasonable
yields (Table 1, entries 13-17). Among these copper salts, CuI
was the best one (Table 1, entry 9). Though a variety of
solvents can be used for this reaction (Table 1, entries 9, 21-
Organic dithiocarbamates are popular in organic chemistry due
to their versatile applications. They have attracted wide attention
since they could be served as important synthetic
[
1]
intermediates, several of which were found to be biologically
[
2]
active, such as monoacylglycerol lipase inhibitors, leukemic
cells inhibitors,[
3]
thymocytes inhibitors,[4] antitumors[5] and
antibacterials.[ Moreover, dithiocarbamates are widely applied
6]
in agriculture sphere, serving as fusarium oxysporum agent,[7]
crop anti-diseases drugs.[8]
24), the results showed DMF was the best solvent. The effect of
Conventionally,
protocols
for
the
synthesis
of
the temperature was checked, rising or decreasing the
temperature led to significant yield decrease (Table 1, entries
25-27). The influence of substrates molar ratio was also
surveyed, 1a:2a=0.5:0.4 was proved to be the optimal (Table 1,
entries 9, 28-29). Furthermore, the control experiments for the
loading of CuI and KOt-Bu showed that increasing the loading of
CuI or KOt-Bu led to almost no yield change (Table 1, entries
dithiocarbamates involve the use of organometallic reagents
with tetramethylthiuram disulfide,[9] sodium salt of dithiocarbamic
acid with diaryliodonium salts[10] or halobenzene.[11] In recent
years, one-pot three component reactions of amines, carbon
disulfide with electrophiles including alkyl halide[12] or aryl
halide,[13]
fluoroborate,[14]
aryl
diazonium
pentafluorobenzonitrile,[15] benzene boronic
acid[16]
were
30, 33), while reducing the loading of CuI or KOt-Bu cause sharp
reported. However, these methods are still limited by multiple
yield decrease (Table 1, entries 31-32, 34). The best reaction
conditions were summarized in Entry 29, Table 1.
reaction steps, flammable and explosive substrate or reagents,
high substrates molar ratio.[17] As part of our longstanding
interests in developing phenylthioureas and the relevant
applications,[18] we hereby report a facile method for the
Table 1 Optimization of the reaction conditionsa
synthesis of S-aryl dithiocarbamates using CuI as catalyst and
KOt-Bu as base. In this protocol, symmetric and asymmetric
diaryliodonium salts react with tetraalkylthiuram disulfides
affording two kinds of S-aryl dithiocarbamates in one pot with
good yields.
S
I
S
N
S
N
S
N
+
N
S
conditions
FG1
FG2
S
S
+
S
OTf
FG1
FG2
3
a
3a'
2a
1a
FG1=H, FG2=H
o
b
Entry
Catalyst
Base
(equiv)
---
Solvent
Temp.( C)
Yiled (%)
(mmol%)
1
2
3
4
5
6
7
8
9
---
H
2
O
110
110
110
110
110
110
110
110
110
25
29
27
30
27
26
65
60
77
[
a]
b]
School of Chemistry and Environmental Engineering, Wuhan
Institute of Technology, Wuhan 430205, China
E-mail: dzb04982@wit.edu.cn
Key Laboratory of Green Chemical Process, Ministry of Education,
Wuhan Institute of Technology, Wuhan 430205, China
---
---
---
---
---
---
EtOH:H
DMSO:H
DMF:H O(1:1)
2
O (1:1)
2
O(1:1)
[
2
CuCl
CuI
CuI
CuI
CuI
2
K
2
CO
---
CO
3
2
H O
DMF
DMF
DMF
DMF
K
2
3
2 3
Cs CO
KOt-Bu
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European Journal of Organic Chemistry
10.1002/ejoc.201701056
FULL PAPER
1
1
1
1
1
1
1
1
1
1
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
CuI
CuI
KOH
Et
CH ONa
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMAC
Toluene
THF
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
100
90
51
62
3
N
Under the optimized reaction conditions, various substituted
S-aryl dithiocarbamates were synthesized smoothly in good
yields (Table 2, 3a-3q). In the case of reaction with
tetramethylthiuram disulfides (TMTD, 2a), the nature of
diphenyliodonium counterion anions showed no effect on the
yields of the products (Table 2, entries 1-3, 5). A series of
symmetrical and unsymmetrical diaryliodonium salts were
CuI
3
46
CuBr
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
57
2
Cu O
67
Cu(OAc)
2
50
CuCl
58
CuCl
FeBr
NiBr
2
48
submitted
for
reaction
survey.
Various
symmetrical
3
25
diaryliodonium salts 1X (X=d, e, f, g) reacted with TMTD (2a)
giving S-aryl dithiocarbamates 3 and 3’ in good yields (Table 2,
entries 4-7). Heterocycle dithiocarbamate (3a’) were not
obtained under standard reaction conditions (Table 2, entry 10).
Tetraethylthiuram disulfide (TETD, 2b) and tetrabutylthiuram
disulfide (TBTD, 2c) could also be arylated to the corresponding
products successfully. Symmetrical diaryliodonium salts (a, d, e,
f, g,) reacted with TETD and TBTD, respectively giving the
desired dithiocarbamates with good yield (entries 11-15 for
TETD, entries 18-22 for TBTD). Unsymmetrical diaryliodonium
salts 1h and 1i were slightly selectively transformed to the
desired products smoothly, and multi-substituted aryl
dithiocarbamates (3e, 3f, 3j, 3l) were more favorably obtained
(Table 2, entries 8-9, 16-17). In general, the reaction was
slightly positively affected by electron donating groups on the
aromatic ring, the steric hindrance from N-substituted amine
group put no effect on the reaction, showing its good substrate
suitability.
2
Mess
Mess
48
Pd(OAc)
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
2
49
44
2
4c
43
2
5
6
7
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
64
2
46
2
120
110
110
110
110
110
110
110
57
8d
2
75
9e
2
84
0f
3
79
1g
3
3
72
2h
59
33i
82
3
4J
43
[
a] Reaction conditions: 1a (0.5 mmol), 2a (0.5mmol), catalyst (30% mmol),
base (2.0 equiv), DMF (2 mL) for 4–6 h. [b] Isolated yield for 3a and 3a’,
respectively. [c] Reaction at 70 oC. [d] With 0.5 mmol of 1a and 0.6 mmol of 2a.
[
e] With 0.5 mmol of 1a and 0.4 mmol of 2a. [f] With CuI (50% mmol). [g] With
CuI (20% mmol). [h] With CuI (10% mmol). [i] With KOt-Bu (3.0 equiv). [j] With
KOt-Bu (1.0 equiv).
Table 2. Synthesis of S-aryl dithiocarbamates from diaryliodonium salts and tetraalkylthiuram disulfides a
S
R3
R3
R3
I
R3
S
N
S
N
S
N
R1
R2
CuI(30%), KOt-Bu(2.0eq)
DMF, 110oC, 4-6h
R3
+
N
S
R3
R3
R1
R2
+
X
R3
S
S
S
X=OTf, Cl, NO3, OTs
2
3
3'
1
Entry
Diaryliodonium
salts
Tetraalkylthiuram
disulfides
Product 3
(Yield %)
Product 3’
(Yield %)
b
c
I
S
S
N
S
N
S
N
1
N
S
S
S
OTf
S
3a: 84%; 86%d
3a: 84%; 86%d
2
a
1a
I
S
S
S
N
N
S
N
N
S
N
N
2
3
N
N
S
S
S
Cl
S
S
2
a
3a: 85%
3a: 85%
1b
I
S
S
S
S
S
S
NO3
1c
3a: 86%
3a: 86%
2
a
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European Journal of Organic Chemistry
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FULL PAPER
I
S
S
N
S
N
S
S
N
4
N
S
S
S
OTf
d
S
3
b: 79%
3b: 79%
1
2
a
I
S
S
S
N
S
N
N
N
5
O
O
N
N
S
S
S
OTs
O
O
S
S
1e
3c: 84%
3c: 84%
2
a
I
S
S
N
S
S
N
S
6
S
OTf
1f
2a
3d: 86%
3d: 86%
I
S
S
S
N
S
N
S
N
N
7
8
N
N
S
S
S
OTf
S
S
3
e: 89%
3e: 89%
2
a
1g
I
S
N
S
N
N
S
S
S
S
OTf
3
e: 86%
3a: 73%
2
a
1
h
N
I
S
S
S
S
S
N
9
N
S
S
S
3
a: 81%
OTf
2a
3f: 89%
1i
S
S
S
S
I
S
N
S
2a
S
N
N
S
N
N
1
0
1
2
N
N
S
S
S
OTf
j
S
S
3
a: 97%
1
3a’: 0%
I
S
S
N
S
1
1
S
OTf
S
1
a
2b
3g: 80%
3g: 80%
I
S
S
S
N
N
S
N
S
N
N
N
S
OTf
S
S
S
S
1
d
2b
3h: 82%
3h: 82%
I
S
N
S
N
S
13
S
S
S
OTf
2b
1
f
3
i: 81%
3i: 81%
S
S
I
S
N
N
S
S
N
S
N
1
4
5
N
N
S
S
S
S
OTf
2
b
3j: 77%
3j: 77%
1g
I
S
S
N
S
N
1
S
O
O
OTs
S
S
O
O
1e
2
b
3k: 76%
3k: 76%
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European Journal of Organic Chemistry
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S
S
I
S
N
N
S
N
S
N
N
1
6
7
N
N
S
S
S
S
S
OTf
I
2
b
3j 86%
3g: 76%
1
h
N
S
S
S
S
1
S
S
3
g: 61%
OTf
2
b
1i
3l: 86%
S
S
I
N
1
8
9
S
S
N
S
N
S
N
OTf
S
S
1a
2c
3m: 83%
3m: 83%
S
S
I
N
S
S
1
S
N
S
N
N
OTf
S
S
1d
2c
3
n: 81%
3n: 81%
S
S
I
N
S
N
S
S
N
20
S
S
N
S
OTf
1f
2c
3o: 75%
3o: 75%
S
S
I
N
2
1
2
S
S
S
N
S
N
N
OTf
g
S
S
1
2c
3p: 81%
3p: 81%
S
S
I
N
2
S
S
S
N
S
N
O
O
N
OTs
S
S
1e
O
O
2c
3q: 87%
3q: 87%
o
[
a] Reaction conditions: 1 (0.5 mmol), 2 (0.4 mmol), CuI (0.15 mmol), KOt-Bu (1.0 mmol), DMF (2 mL) at 110 C for 4-6 h. [b] Isolated yield. [c] Isolated yield. [d]
A scaled-up reaction (diaryliodonium salt 1: 10 mmol) was performed.
CuI
A
The possible reaction mechanism (Scheme 1) is proposed
2
1
Ar SR
literature.[
16,
19]
Ar SR1
Ar1IAr2OTf
1
according to the related
At first,
3
3'
1
diphenyliodonium triflate (1) react with CuI (A) generating
intermediates B (through an oxidative addition manner) and aryl
iodobenzene E. Tetraalkylthiuram disulfide (2) and B undergo
through transmetallation affording complex C. Under the action
of base (KOt-Bu), complex C decomposed to intermediate D
2
Ar I
OTf
E
Ar -CuIII-I
1
B
I
R -S-S-R1
1
Ar -CuIII-S-R1 + KI
2
2
H
OTf
I
and potassium salt G,
a
following reductive elimination
Ar -CuIII-I
1
Ar -CuIII-I
2
produced the final product 3 along with copper (I) species A.
On the other hand, A and E go the same oxidative addition
affording F, then transmetallation giving intermediate H, and the
reductive elimination producing the other main product 3’ along
with copper(I) species A.
F
R1-S-S-R1
C
S
I
KOt-Bu
R1=
C N
Ar -CuIII-S-R1 + OTf + R SK
1
1
D
G
Scheme 1. Plausible mechanism for copper catalyzed S-arylation of
tetraalkylthiuram disulfides by using diaryliodonium salts.
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European Journal of Organic Chemistry
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Conclusions
2, 5-Dimethylphenyl dimethylcarbamodithioate (3d). According to TP,
the residue was purified by flash chromatography on silica gel (EtOAc/
PE= 1:8) to give the target compound 3d (96.8 mg, 86%) as colorless oil,
To summarize, we report an efficient and convenient procedure
for the synthesis of S-aryl dithiocarbamates from diaryliodonium
salts and tetraalkylthiuram disulfides. In the presence of
CuI/KOt-Bu, two kinds of S-aryl dithiocarbamates could be
obtained in good yields without obvious selectivity. The reaction
has advantages of efficiency, good atomic economy and broad
substrate scope. The method might afford an alternative way
for the fast preparation of some potentially biologically active
compounds.
1H NMR (400 MHz, CDCl
): δ = 7.33-7.27 (m, 3 H), 3.58 (s, 3 H), 3.51 (s,
H), 2.45 (s, 3 H), 2.41 (s, 3 H). 13C NMR (100 MHz, CDCl
): δ = 196.4,
40.7, 138.1, 136.2, 131.6, 130.8, 130.6, 45.6, 42.1, 20.9, 20.5. HRMS
(225.0646), found: 225.0652.
3
3
1
3
(ESI) calcd for C10
H
16NOS
2
2, 4, 6-Trimethylphenyl dimethylcarbamodithioate (3e). According to TP,
the residue was purified by flash chromatography on silica gel (EtOAc/
PE= 1:7) to give the target compound 3e (106.4 mg, 89%) as white solid;
mp: 77-78 oC, 1H NMR (400 MHz, CDCl
): δ = 7.00 (s, 2 H), 3.53 (s, 6
H), 2.32 (d, J = 16.0 HZ, 9 H), 13C NMR (100 MHz, CDCl
): δ = 196.0,
43.8, 140.4, 129.3, 127.5, 45.5, 42.0, 21.6, 21.4. HRMS (ESI) calcd for
(239.0802), found: 239.0809.
3
3
1
12 2
C H17NS
Experimental Section
2
, 4, 6-triisopropylphenyl dimethylcarbamodithioate (3f). According to
TP, the residue was purified by flash chromatography on silica gel
EtOAc/ PE= 1:7) to give the target compound 3f (143.8 mg, 89%) as
Nuclear magnetic resonance (NMR) spectra were obtained on a Bruker
AC 400 MHz spectrometer ( H NMR at 400 Hz, 13C NMR at 100 Hz) in
1
(
CDCl
3
using tetramethylsilane as an internal standard. Chemical shifts
o
1
colorless solid; mp: 122-124 C, H NMR (400 MHz, CDCl
3
): δ = 7.04 (s,
H), 3.47 (s, 6 H), 3.38-3.32 (m, 2 H), 2.90-2.84 (m, 2 H), 1.21 (d, J =
.0 Hz, 6 H), 1.41 (s, 12 H). 13C NMR (100 MHz, CDCl
): δ = 197.7,
53.4, 151.3, 125.7, 122.1, 45.5, 42.0, 34.2, 31.9, 23.8. HRMS (ESI)
(323.1741), found: 323.1749.
are given in ppm and coupling constants (J) are given in Hz.
Electrospray ionization-high-resolution mass spectra (ESI-HRMS) were
determined on an Ion Spec (7.0 T) spectrometer. All reactions were
performed under dried glassware with septums. All starting materials
were purchased from commercial suppliers and used without further
purification unless otherwise stated. Yield refers to isolated compounds
2
8
1
3
calcd for C18H29NS
2
Phenyl diethylcarbamodithioate (3g). According to TP, the residue was
purified by flash chromatography on silica gel (EtOAc/ PE= 1:10) to give
the target compound 3g (90.0 mg, 80%) as pale yellow oil, 1H NMR
1
estimated to be > 95% pure as determined by H NMR and capillary GC
analysis.
(
400 MHz, CDCl
3
): δ = 7.48 (d, J = 12.0 Hz, 5 H), 4.02 (d, J = 4.0 Hz, 2
Typical procedure (TP) for the preparation of S-aryl
dithiocarbamates in the presence of Cu and KOt-Bu.
Diphenyliodonium triflate (0.5 mmol), TMTD (0.4 mmol), CuI (30% mmol),
KOt-Bu (2.0 equiv.) were added in dried seal tube equipped with a septum and
magnetic stirrer bar, DMF (2 mL) was then added. The mixture was stirred at
H), 3.84 (d, J = 8.0 Hz, 2 H), 1.39 (t, J = 4.0 Hz, 3 H), 1.29 (d, J = 4.0 Hz,
3
4
H). 13C NMR (100 MHz, CDCl
9.9, 47.3, 12.8, 11.6. HRMS (ESI) calcd for C11 (225.0604),
3
): δ = 195.9, 137.2, 131.6, 130.0, 129.0,
H15NS
2
found: 225.0608.
1
10 °C and checked by thin-layer chromatography (TLC) until the starting
material was finished (about 4-6 h). The reaction was cooled down to room
temperature, quenched with sat. NH Cl solution (5 mL), and then extracted
with EtOAc (10 mL). The crude solution was dried over anhydrous Na SO and
4
-Methylphenyl diethylcarbamodithioate (3h). According to TP, the
residue was purified by flash chromatography on silica gel (EtOAc/ PE=
4
1:15) to give the target compound 3h (98.0 mg, 82%) as white solid; mp:
2
4
o
1
3
75-76 C, H NMR (400 MHz, CDCl ): δ = 7.28 (d, J = 8.0 Hz, 2 H), 7.16
evaporated under vacuum. The residue was purified by flash column
chromatography to afford the desired product.
(
2
(
d, J = 4.0 Hz, 2 H), 3.94 (d, J = 8.0 Hz, 2 H), 3.76 (d, J = 4.0 Hz, 2 H),
.32 (s, 3 H), 1.31 (t, J = 4.0 Hz, 3 H), 1.20 (t, J = 4.0 Hz, 3 H). 13C NMR
100 MHz, CDCl ): δ = 196.5, 140.2, 137.0, 129.9, 128.1, 49.9, 47.2,
3
Phenyl dimethylcarbamodithioate (3a). According to TP, the residue was
purified by flash chromatography on silica gel (EtOAc/ PE= 1:7) to give
the target compound 3a (82.7 mg, 84%) as white solid; mp: 91-92 oC,
2
1.5, 12.7, 11.6. HRMS (ESI) calcd for C12
2
H17NS (239.0802), found:
239.0807.
1H NMR (400 MHz, CDCl
): δ = 7.49-7.45 (m, 5 H), 3.56 (s, 3 H), 3.50 (s,
H). 13C NMR (100 MHz, CDCl
): δ = 197.6, 137.0, 131.7, 130.1, 129.1,
3
2, 5-Dmethylphenyl diethylcarbamodithioate (3i). According to TP, the
3
4
1
3
residue was purified by flash chromatography on silica gel (EtOAc/ PE=
5.7, 42.0. HRMS (ESI) calcd for
97.0337.
9 2
C H11NS (197.0333), found:
1
:15) to give the target compound 3i (102.5mg, 81%) as pale yellow oil,
1
H NMR (400 MHz, CDCl
.93 (d, J = 4.0 Hz, 2 H), 3.77 (d, J = 8.0 Hz, 2 H), 2.25 (d, J = 8.0 Hz, 6
H), 1.31 (s, 3 H), 1.19 (s, 3 H). 13C NMR (100 MHz, CDCl
): δ = 195.0,
40.7, 138.2, 136.2, 131.4, 130.6, 130.5, 49.7, 47.3, 20.8, 20.4, 12.8,
1.7. HRMS (ESI) calcd for C13 (253.0959), found: 253.0962.
3
): δ = 7.18 (s, 1 H), 7.11 (d, J = 8.0 Hz, 2 H),
3
4-Methylphenyl dimethylcarbamodithioate (3b). According to TP, the
3
residue was purified by flash chromatography on silica gel (EtOAc/ PE=
1
1
1
1
7
:8) to give the target compound 3b (83.3 mg, 79%) as white solid; mp:
09-110 oC, 1H NMR (400 MHz, CDCl
): δ = 7.33 (d, J = 8.0 HZ, 2 H),
.33 (d, J = 4.0 HZ, 2 H), 3.51 (s, 3 H), 3.44 (s, 3H), 2.37 (s, 3H). 13C
): δ = 198.1, 140.4, 136.8, 130.0, 128.3, 45.7,
2.0. HRMS (ESI) calcd for C10 (211.0498), found: 211.0489.
H18NS
2
3
2, 4, 6-Trimethylphenyl diethylcarbamodithioate (3j). According to TP,
NMR (100 MHz, CDCl
3
the residue was purified by flash chromatography on silica gel (EtOAc/
PE= 1:15) to give the target compound 3j (102.8mg, 77%) as yellow
solid; mp: 94-96 C, 1H NMR (400 MHz, CDCl
4
4
H11NS
2
o
3
): δ = 6.93 (s, 2 H), 3.96
-Methoxyphenyl dimethylcarbamodithioate (3c). According to TP, the
(
1
1
d, J = 8.0 Hz, 2 H), 3.82 (d, J = 4.0 Hz, 2 H), 2.28 (s, 6 H), 2.24 (s, 3 H),
residue was purified by flash chromatography on silica gel (EtOAc/ PE=
.34 (s, 3 H), 1.20 (s, 3 H). 13C NMR (100 MHz, CDCl
3
): δ = 194.3,
43.9, 140.3, 129.2, 127.6, 49.7, 47.2, 21.7, 21.3, 12.9, 11.8. HRMS
(267.1115), found: 267.1114.
1
:7) to give the target compound 3c (95.3 mg, 84%) as white solid; mp:
o
1
3
97-99 C, H NMR (400 MHz, CDCl ): δ = 7.37 (d, J = 4.0 HZ, 2 H), 6.96
(ESI) calcd for C14
H21NS
2
(
(
4
d, J = 4.0 HZ, 2 H), 3.83 (s, 3 H), 3.54 (s, 3H), 3.48 (s, 3H). 13C NMR
100 MHz, CDCl ): δ = 198.7, 161.1, 138.4, 122.6, 114.7, 55.3, 45.8,
1.9. HRMS (ESI) calcd for C10 (227.0439), found: 227.0441.
3
H11NOS
2
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European Journal of Organic Chemistry
10.1002/ejoc.201701056
FULL PAPER
4
-Methoxy diethylcarbamodithioate (3k). According to TP, the residue
Hz, 2 H), 3.86 (s, 2 H), 3.75 (s, 3 H), 3.69 (t, J = 4.0 Hz, 2 H), 1.76-1.72
(m, 4 H), 1.38-1.23 (m, 4 H), 0.93 (t, J = 8.0 Hz, 3 H), 0.86 (t, J = 8.0 Hz,
was purified by flash chromatography on silica gel (EtOAc/ PE= 1:7) to
give the target compound 3k (97.0mg, 76%) as white solid; mp: 73-75
3 H). 13C NMR (100 MHz, CDCl
55.5, 55.3, 52.9, 29.6, 28.4, 20.1, 13.9, 13.8. HRMS (ESI) calcd for
16 2
C H25NOS (311.1378), found: 311.1375.
3
): δ = 197.4, 161.0, 138.6, 122.6, 114.6,
oC, 1H NMR (400 MHz, CDCl
): δ = 7.23 (d, J = 8.0 Hz, 2 H), 6.80 (d, J
8.0 Hz, 2 H), 3.87 (d, J = 8.0 Hz, 2 H), 3.68 (s, 5 H), 1.24 (t, J = 6.4 Hz,
H), 1.13 (t, J = 6.4 Hz, 3 H). 13C NMR (100 MHz, CDCl
): δ = 197.1,
61.0, 138.6, 122.4, 114.6, 55.3, 50.0, 47.1, 12.7, 11.6. HRMS (ESI)
(255.0752), found: 255.0759.
3
=
3
1
3
calcd for C12H17NOS
2
Acknowledgements
2
, 4, 6-Triisopropylphenyl diethylcarbamodithioate (3l). According to TP,
We thank the foundation support from National Natural Science
Foundation of China (21302150), Hubei Provincial Department
of Education (D20131501), Scientific Research Foundation for
the Returned Overseas Chinese Scholars, State Education
the residue was purified by flash chromatography on silica gel (EtOAc/
PE= 1:20) to give the target compound 3l (150.9mg, 86%) as yellow
solid; mp: 58-59 oC, H NMR (400 MHz, CDCl
1
3
): δ = 7.02 (s, 2 H), 3.94
(
2
d, J = 4.0 Hz, 2 H), 3.85 (d, J = 8.0 Hz, 2 H), 3.38-3.31 (m, 2 H), 2.89-
.84 (m, 1H), 1.34 (s, 3 H), 1.21 (d, J = 4.0 Hz, 9 H), 1.14 (s, 12 H) 13C
): δ = 196.0, 153.4, 151.1, 125.9, 122.0, 49.6,
7.2, 34.3, 32.0, 23.8, 13.0, 11.8. HRMS (ESI) calcd for C20
351.2054), found: 351.2047.
Ministry [2012]1707 and foundation of
High-end Talent
NMR (100 MHz, CDCl
4
(
3
Cultivation Program from Wuhan Institute of Technology. We
also thank Prof AiwenLei at Wuhan University (China) and for
his kind NMR analysis support, and Prof. Dr. Georg
H33NS
2
Manolikakes
(Germany) for generous chemicals donation.
at
Johann Wolfgang Goethe-Universität
Phenyl dibutylcarbamodithioate (3m). According to TP, the residue was
purified by flash chromatography on silica gel (EtOAc/ PE= 1:20) to give
the target compound 3m (116.6mg, 83%) as brown oil, 1H NMR (400
MHz, CDCl
3
): δ = 7.40-7.33 (m, 5 H), 3.85 (t, J = 4.0 Hz, 2 H), 3.67 (t, J
4.0 Hz, 2 H), 1.72-1.64 (m, 4 H), 1.35-1.25 (m, 4H), 0.93 (t, J = 4.0 Hz,
H), 0.85 (t, J = 8.0 Hz, 3 H). 13C NMR (100 MHz, CDCl
): δ = 196.2,
37.1, 131.8, 129.9, 129.0, 55.3, 53.1, 29.6, 28.4, 20.2, 13.9, 13.8.
(281.1272), found: 281.1280.
Keywords: dithiocarbamates • aylation• diaryliodonium salts •
tetraalkylthiuram disulfides • copper
=
3
1
3
References
HRMS (ESI) calcd for C15H23NS
2
[
1] a) U. Boas, H. Gertz, J. B. Christensen, P. M. H. Heegaard, Tetrahedron
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Grainger, Chem. Eur. J. 2014, 20, 6505-6517.
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residue was purified by flash chromatography on silica gel (EtOAc/ PE=
:20) to give the target compound 3n (119.5mg, 81%) as brown oil, 1
[2]
C. N. Kapanda, J. Masquelier, G. Labar, G. G. Muccioli, J. H. Poupaert,
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H
3
NMR (400 MHz, CDCl ): δ = 7.31 (d, J = 4.0 Hz, 2 H), 7.19 (d, J = 8.0
Hz, 2 H), 3.89 (t, J = 4.0 Hz, 2 H), 3.71 (t, J = 8.0 Hz, 2 H), 2.35 (s, 3H),
[
3]
R. Bessho, K. Matsubara, M. Kubota, K. Kuwakado, H. Hirota, Y.
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1
.76-1.68 (m, 4 H), 1.41-1.27 (m, 4 H), 0.96 (t, J = 8.0 Hz, 3 H), 0.89 (t,
J = 8.0 Hz, 3 H). 3C NMR (100 MHz, CDCl
1
3
): δ = 196.8, 140.1, 136.9,
[
[
4]
5]
J. T. Wolfe, D. ROSS, G. M. Cohen, FEBS Lett. 1994, 352, 58-62.
a) L. Ronconi, C. Marzano, P. Zanello, M. Corsini, G. Miolo, C. Macca`,
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129.9, 128.3, 55.4, 53.0, 29.6, 28.4, 21.5, 20.2, 13.9, 13.8. HRMS (ESI)
calcd for C16 (295.1428), found: 295.1435.
H25NS
2
2, 5-Dmethylphenyl dibutylcarbamodithioate (3o). According to TP, the
residue was purified by flash chromatography on silica gel (EtOAc/ PE=
[
6]
a) N. G. Urlyapova, A. A. Yushchenko, A. D. Daudova, V. A. Makarov,
Bull. Exp. Biol. Med. 2007, 143, 327-329; b) R. Nagano, K. Shibata, T.
Naito, A. Fuse, K. Asano, T. Hashizume, S. Nakagawa, Antimicrob.
Agents. Chemother. 1997, 41, 2278-2281.
1
:30) to give the target compound 3o (115.9mg, 75%) as colorless oil,
1
3
H NMR (400 MHz, CDCl ): δ = 7.17 (s, 1 H), 7.13-7.08 (m, 2 H), 3.86 (t,
J = 8.0 Hz, 2 H), 3.69 (t, J = 4.0 Hz, 2 H), 2.44 (d, J = 4.0 Hz, 6 H), 1.73-
1
8
1
1
.63 (m, 4 H), 1.37-1.23 (m, 4 H), 0.92 (t, J = 4.0 Hz, 3 H), 0.85 (t, J =
.0 Hz, 3 H). 13C NMR (100 MHz, CDCl
): δ = 195.3, 140.6, 138.2,
36.1, 131.4, 130.8, 130.5, 55.1, 53.0, 29.7, 28.5, 20.8, 20.4, 20.1, 13.9,
3.8. HRMS (ESI) calcd for C17 (309.1585), found: 309.1582.
[
[
[
7] C. Rafin, E. Veignie, M. Sancholle, D. Postel, C. Len, P. Villa, G. Ronco,
J. Agric. Food Chem. 2000, 48, 5283-5287.
3
8] C. Len, D. Postel, G. Ronco, P. Villa, J. Agric. Food Chem. 1997, 45, 3-
H27NS
2
6.
9]
a) S. Gronowitz, A. B. Hornfeldt, M.Temciuc, Synthesis 1993, 5, 483-
2, 4, 6-Trimethylphenyl dibutylcarbamodithioate (3p). According to TP,
484; b) A. Krasovskiy, A. Gavryushin, P. Knochel. Synlett. 2005, 17,
the residue was purified by flash chromatography on silica gel (EtOAc/
2691-2693; c) A. Krasovskiy, V. Malakhov, A. Gavryushin, P. Knochel,
PE= 1:30) to give the target compound 3p (130.8mg, 81%) as colorless
Angew. Chem. Int. Ed. 2006, 45, 6040-6044.
oil, 1H NMR (400 MHz, CDCl
3
): δ = 6.94 (s, 2 H), 3.90 (t, J = 8.0 Hz, 2
[
[
[
[
[
10] Z. C. Chen, Y. Y. Jin, P. J. Stang, J. Org. Chem. 1987, 52, 4117-4118.
11] Y. Y Liu , W. L. Bao, Tetrahedron Lett. 2007, 48, 4785-4788.
H), 3.75 (t, J = 8.0 Hz, 2 H), 2.30 (s, 6 H), 2.25(s, 3 H), 1.76 (d, J = 8.0
Hz, 2 H), 1.65 (d, J = 8.0 Hz, 2 H), 1.42-1.36 (m, 2 H), 1.31-1.26 (m, 2
H), 0.96 (t, J = 4.0 Hz, 3 H), 0.89 (t, J = 8.0 Hz, 3 H). 13C NMR (100
12] N. Azizi, F. Aryanasab, M. R. Saidi, Org. Lett. 2006, 8, 5275-5277.
13] S. Bhadra, A. Saha, B. C. Ranu, Green Chem. 2008, 10, 1224-1230.
14] T. Chatterjee, S. Bhadra, B. C. Ranu, Green Chem. 2011, 13, 1837-
MHz, CDCl
8.6, 21.7, 21.4, 20.2, 13.9, 13.9. HRMS (ESI) calcd for C18
323.1741), found: 323.1746.
3
): δ = 194.7, 140.6, 143.8, 140.2, 129.2, 55.0, 52.9, 29.8,
2
(
H29NS
2
1
842.
15] X. G. Yin, Y. M. Guo, C. B. Liu, Z. F. Wang, B. Zhang. Tetrahedron Lett.
015, 56, 5135-5139.
[
2
4
-Methoxy phenyl dibutylcarbamodithioate (3q). According to TP, the
[16] C. R. Qi, T. Z. Guo, W. F. Xiong, Synlett. 2016, 27, 2626-2630.
[17] D. Chaturvedi, S. Ray, Tetrahedron Lett. 2006, 47, 1307-1309.
[18] a) C. Z. Chang, W. Xu, M. T. Zeng, M. Liu, X. Liu, H. Zhu, Z. B. Dong,
Synthetic. Commun. 2017, 47, 1262-1267; b) W. Xu, M. T. Zeng, M.
residue was purified by flash chromatography on silica gel (EtOAc/ PE=
:20) to give the target compound 3q (135.3mg, 87%) as yellow oil, 1
NMR (400 MHz, CDCl ): δ = 7 .29 (d, J = 8.0 Hz, 2 H), 6.87 (d, J = 12.0
1
H
3
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European Journal of Organic Chemistry
10.1002/ejoc.201701056
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Liu, X. Liu, C. Z. Chang, H. Zhu, Y. S. Li, Z. B. Dong, Chem. Lett.
Zeng, M. Liu, S. S. Liu, Y. S. Li, Z. B. Dong, Synthesis 2017, 49, 3084-
2017, 46, 641-643; c) M. T. Zeng, W. Xu, M. Liu, X. Liu, C. Z. Chang,
3090.
H. Zhu, Z. B. Dong, SynOpen 2017, 1, 1-7; d) Q. Cao, F. Liu, M. Wang,
W. Xu, M. T. Zeng, M. Liu, Y. S. Li, Z. B. Dong, J. Chem. Res. 2017,
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European Journal of Organic Chemistry
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Entry for the Table of Contents (Please choose one layout)
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Text for Table of Contents
Key Topic*
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
((Insert TOC Graphic here: max.
width: 5.5 cm; max. height: 5.0 cm;
NOTE: the final letter height should
not be less than 2 mm.))
*one or two words that highlight the emphasis of the paper or the field of the study
Layout 2:
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S-arylation of disulfides*
Meng-Tian Zeng, Wan Xu, Xing Liu, Cai-
Zhu Chang, Hui Zhu, Zhi-Bing Dong*
S
R3
N
S-arylation of disulfides
R3
N
R3
N
I
R3
S
S
S
R1
R2
CuI(30%), KOt-Bu(2.0eq)
DMF, 110oC, 4-6h
R3
+
N
S
R3
R3
R1
R2
+
X
R3
S
S
S
R3=Me, Et, nBu
Page No. – Page No.
X=OTf, Cl, NO3, OTs
Yields: 61-89%, 22 examples
Copper-catalyzed S-arylation
of tetraalkylthiuram disulfides
by using diaryliodonium salts
An efficient and convenient procedure for the S-arylation of tetraalkylthiuram
disulfides by using diaryliodonium salts was explored. In the presence of CuI/KOt-
Bu, two kinds of S-aryl dithiocarbamates could be obtained with good to excellent
yields at one time, showing no obvious selectivity. The methodology has
advantages of efficiency, good atomic economy and broad substrate scope.
*one or two words that highlight the emphasis of the paper or the field of the study
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