Chemoselective C–S/S–S Formation between Diaryl Disulfides and Tetraalkylthiuram Disulfides

Article abstract of DOI:10.1002/ejoc.201901401

An efficient C–S/S–S formation for the chemoselective synthesis of aryl dithiocarbamate (C–S formation) and aryl dialkylcarbamo(dithioperoxo)thioate (S–S formation) was studied. The chemoselectivity could be controlled by modulating the reaction temperature, base, and catalyst. The transformation features a simple reaction, easily available starting materials, high selectivity and easy performance, showing its practical synthetic value for the preparation of some potential biologically or pharmaceutically active compounds.

Full text of DOI:10.1002/ejoc.201901401

A Journal of
Accepted Article
Title: Chemo-selective C-S/S-S Formation between Diaryl Disulfides
and Tetraalkylthiuram Disulfides
Authors: Kang Peng, Hui Zhu, Xing Liu, Han-Ying Peng, Jin-Quan
Chen, and Zhi-Bing Dong
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901401
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901401
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10.1002/ejoc.201901401
European Journal of Organic Chemistry
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Chemo-selective C-S/S-S Formation between Diaryl Disulfides
and Tetraalkylthiuram Disulfides
Kang Peng,[a] Hui Zhu,[a] Xing Liu,[a] Han-Ying Peng, [a] Jin-Quan Chen,[a] and Zhi-Bing Dong* [a],[b],[c]
Abstract: An efficient C-S/S-S formation for the chemo-selective
synthesis of aryl dithiocarbamate (C-S formation) and aryl
dialkylcarbamo(dithioperoxo)thioate (S-S formation) was studied.
The chemo-selectivity could be controlled by modulating the reaction
temperature, base, and catalyst. The transformation features simple
performance, easily available starting material, high selectivity and
easy performance, showing its practical synthetic value for the
preparation of some potential biologically or pharmaceutically active
compounds.
reports
for
the
synthesis
of
dialkylcarbamo(dithioperoxo)thioate.[13] Typical approaches to
aryl dithiocarbamates involve the coupling reaction of one-pot
three-component reactions using amines and carbon disulfide
with electrophiles, including alkyl[14] or aryl halides,[15]
arenediazonium fluoroborates,[16] N-(phenylthio)phthalimide[17]
and arylboronic acids.[18] Although remarkable progress has
been made, these methods are still limited by tedious operation
steps, flammable and explosive substrates or reagents, and high
substrate molar ratios. Therefore, it would be still attractive to
explore more effective and mild methods, especially the ones
starting from easily available materials and inexpensive
catalysts. As part of our longstanding interest in developing
Introduction
organosulfur
chemistry
and
exploring
their
relevant
Organosulfur compounds are widely used in medicines,
pesticides and biological study.[1] Among these, dithiocarbamate
derivatives have become the focus of research interest due to
their significant biological activity.[2] Many compounds containing
this skeleton have been reported to be biologically active, such
as monoacylglycerol lipase inhibitors (a, c),[3] leukemic cells
inhibitors,[4] thymocytes inhibitors,[5] antitumor agents,[6] and
antibacterial agents (Figure 1).[7] In addition, they are an
important class of versatile synthetic intermediates in organic
synthesis,[8] they have also been used as linkers in solid-phase
organic synthesis,[9] as protection groups in peptide synthesis,[10]
and recently in the synthesis of ionic liquids.[11] Moreover,
dialkylcarbamo(dithioperoxo)thioates are reported to show anti-
filarial activities (b) (Figure 1).[12]
applications,[19] we report here a protocol for the selective
synthesis of dithiocarbamates (C-S formation) and aryl
dialkylcarbamo(dithioperoxo)thioates (S-S formation) starting
from diaryl disulfides and tetraalkylthiuram disulfides (TATD).
The synthesis selectivity could be controlled by modulating the
reaction temperature, base, and catalyst. It is worthy to note that
the efficiency and easy performance make the protocol attractive
for the selective preparation of S-arylated or S-S-arylated
dithiocarbamates.
Results and Discussion
Diphenyl disulfide (1a) and tetramethylthiuram disulfide (TMTD,
2a) were selected as the starting materials to explore the
possible C-S/S-S formation, the isolated yields were calculated
based on PhS group since both substrates are symmetrical
disulfides. Gratifyingly, the desired product aryl dithiocarbamates
(3a) was obtained in 42% yield when the reaction was
conducted in the presence of K2CO3 in DMF at 120 oC (Table 1,
entry 1). To optimize the synthesis conditions of S-aryl
dithiocarbamate (C-S formation), the effect of bases were
evaluated (entries 2−4), and K2CO3 was proved to be the
optimal. The examination of solvents (entries 1, 5-7) and
reaction temperature (entries 1, 8-10) showed that N, N-
o
dimethylformamide (DMF) was the best solvent, 120 C was the
optimal reaction temperature. By increasing the base loading did
not promote the yield (entry 11-12), and the addition of a catalyst
showed a slight yield increase (entry 13). Encouraged by these
results, several transition metal catalysts were surveyed (entries
14-26), and the best one was CuI (10 mol% yields in 65%).
Thus, the optimized reaction conditions were summarized as
follows, diphenyl disulfide (1a, 1 mmol) and tetramethylthiuram
disulfide (2a, 1.2 mmol), CuI (10 mol %) and K2CO3 (2.0 eq.) in
DMF (2 mL) at 120 °C for 24 hours (entry 25).
Figure 1. Representative organic dithiocarbamates with biological activity.
So far, a variety of methods are successfully employed for the
synthesis of aryl dithiocarbamates, while there are very few
[a]
[b]
[c]
School of Chemistry and Environmental Engineering, Wuhan
Institute of Technology, Wuhan 430205, China.
Key Laboratory of Green Chemical Process, Ministry of Education,
Wuhan Institute of Technology, Wuhan 430205, China
Ministry-of-Education Key Laboratory for the Synthesis and
Application of Organic Functional Molecules, Hubei University,
Wuhan 430062, China.
Table 1. Optimization of reaction conditions for the synthesis of 3a[a]
Email: dzb04982@wit.edu.cn
https://cee.wit.edu.cn/info/1052/1538.htm
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10.1002/ejoc.201901401
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Entry
Catalyst
(mol%)
Base
Solvent
Temp[°C]
Yield
(%)[b]
42
31
27
36
Less
31
N.R.
24
35
41
40
41
48
40
29
27
52
64
53
42
53
54
37
39
65
1
2
3
4
5
6
7
8
9
10
11[c]
12[d]
13
14
15
16
17
18
19
20
21
22
23
24
25
26
-
-
-
-
-
-
-
-
-
K2CO3
Cs2CO3
Na2CO3
t-BuOK
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMF
DMF
DMF
DMF
DMAc
DMSO
Toluene
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
120
120
120
120
120
120
120
80
100
130
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
2
3
4
5
6
7
8
3b：66%
2a
2a
2a
2b
2b
2b
2b
1b
1c
3c：52%
3d：49%
-
-
-
PdCl2(20)
PdBr2(20)
NiCl2(20)
CuCl2(20)
Cu2O(20)
CuI(20)
CuBr(20)
PdCl2(10)
NiBr2(10)
CoBr2(10)
Pd(OAc)2(10)
Cu2O(10)
CuI(10)
CuBr(10)
1d
1a
3e：57%
3f：59%
3g：55%
42
[a] Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), catalyst (mol%), base
(2.0 equiv), solvent (2 mL), stirred for 24 hours. [b] Isolated yields based on
PhS group. [c] Base (3.0 equiv). [d] Base (4.0 equiv).
1b
1c
With the optimal reaction conditions in hand, the substrate
scope was investigated. As shown in Table 2, a variety of
substituted diphenyl disulfides reacted with tetraalkylthiuram
disulfides (2, TATD), giving the desired products with moderate
to good yields (Table 2, entries 1-8). Electron-donating groups
attached to the aryl ring of diphenyl disulfides promoted the
reaction slightly (entry 2). Electron-withdrawing groups
deactivated the diphenyl disulfides, providing the products in
lower yields (entries 3-4). In addition, tetraethylthiuram disulfide
(2b, TETD) was also suitable for C-S formation under standard
reaction conditions. The corresponding products were obtained
in slightly lower yields due to the possible steric hindrance from
the alkyl group of the tetraethylthiuram disulfides (entries 5-8).
The yields of aryl dithiocarbamates obtained by using this
protocol are lower than our previous ones,[18d-18h] while it might
offer an alternative way for the construction of these important
compounds.
3h：47%
1d
[a] Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), CuI (10 mmol%), K2CO3
(2.0 equiv), DMF (2 mL), stirred at 120℃ for 24 hours. [b] Isolated yields
based on PhS group.
To our delight, when the temperature dropped to 60 °C, the S-S
bond formation product dimethylcarbamo(dithioperoxo)thioate
(4a) was produced (Table 3, entry 1) under the above standard
reaction conditions, and the yield could be increased to 40%
when the model reaction was conducted at room temperature
(entry 2). Several different catalysts were subsequently tried，
and no significant yields increase were found (entries 3-6). With
no addition of catalyst or base, the yield dropped slightly (entries
7−8), which indicated that the base or catalyst was not crucial for
the reaction. The solvents screening showed that DMF afforded
the best result (entries 9-15). Lastly, the substrate ratio of 1a to
2a was examined (entries 5, 16-17), and it turned out that the
optimal ratio (1a:2a) was 1:1.2 (entry 16). The optimal reaction
Table 2. Substrate scope for the synthesis of aryl dithiocarbamates 3[a]
Tetraalkylthiuram
disulfide
Product
Entry
Diphenyl disulfide
Yield(%)[b]
conditions
for
the
synthesis
of
aryl
1
dialkylcarbamo(dithioperoxo)thioate are summarized in entry 16.
3a：65%
2a
1a
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Table 3. Optimization of reaction conditions for the synthesis of 4a[a]
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2b
2b
2b
2b
4b：67%
4c：73%
4d：75%
4e：53%
1b
1c
Entry
Catalyst
Base
Solvent
Temp[°C]
Yield
(%)[b]
31
40
52
51
41
48
47
48
54
N.R.
Less
53
1
2
3
4
5
6
7
8
9
10
11
12
13
CuI
CuI
PdCl2
Cu(OAc)2
NiBr2
CoBr2
-
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
-
-
-
-
-
-
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH2Cl2
MeCN
DMSO
1,4-
Dioxane
Toluene
Acetone
DMF
60
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
PdCl2
1d
-
-
-
-
-
N.R.
1e
1a
14
15
16[c]
17[d]
-
-
-
-
-
-
-
-
r. t.
r. t.
r. t.
r. t.
N.R.
Mess
66
DMF
61
[a] Reaction conditions (for entries 1–12): 1a (1 mmol), 2a (1 mmol), catalyst
(10 mol%), base (2.0 equiv),solvent(2 mL), stirred for 24 hours. [b] Isolated
yields based on PhS group. [c]: 1a (1 mmol), 2a (1.2 mmol). [d]: 1a (1 mmol),
2a (1.5 mmol).
4f：64%
4g：70%
Under the optimized reaction conditions, the scope of the
substrates
dialkylcarbamo(dithioperoxo)thioates was investigated (Table 4).
In general, the substituted diphenyl disulfides reacted well with
tetraalkylthiuram
dialkylcarbamo(dithioperoxo)thioates in moderate to good yields.
To our delight, diphenyl disulfides bearing electron-withdrawing
groups such as F gave the products in good yields (entry 3-4).
Diphenyl disulfides bearing multiple electron-withdrawing groups
such as Cl gave the products in moderate yields (entries 5 and
9). Generally, due to the possible steric hindrance from the alkyl
group of the tetraethylthiuram disulfides, the corresponding
products were obtained in slightly lower yields (entries 6-9).
for
the
synthesis
of
aryl
1b
1c
disulfides,
furnishing
aryl
4h：55%
4i：52%
1e
[a] Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), DMF (2 mL), stirred at r. t.
Table
4.
Substrate
scope
for
the
synthesis
of
aryl
for 24 hours. [b] Isolated yields based on PhS group.
dimethylcarbamo(dithioperoxo)thioates 4[a]
Tetraalkylthiuram
disulfide
Product
Entry
Diphenyl disulfide
Yield (%)[b]
Figure 2. X-ray crystallography of S-S bond formation product 4b.
To further confirm the S-S bond formation, the product 4b was
characterized by X-ray crystallography (Figure 2, CCDC
1962450).
1
2a
4a：66%
1a
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7.55-7.48 (m, 5H), 3.54 (s, 3H), 3.45 (s, 3H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 197.2, 137.1, 131.9, 130.1, 129.2, 45.8, 42.2 ppm. HRMS
(ESI) m/z [M+H]+ Calcd for C9H12NS2 (198.0406); found: 198.0409.
Conclusions
In summary, an efficient C-S/S-S formation for the chemo-
selective synthesis of aryl dithiocarbamates and aryl
dialkylcarbamo(dithioperoxo)thioates
approach uses inexpensive and readily available diphenyl
disulfides and tetramethyl thiuram disulfides as starting materials,
4-Methylphenyl dimethylcarbamodithioate (3b)[19f]: According to TP1,
the residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 5:1) to give the target compound 3b 279 mg (yield:
was
reported.
The
1
66 %), a white solid. M.p.: 110-112 ℃. H NMR (400 MHz, CDCl3 ): δ =
a
series
of
17
aryl
dithiocarbamates
and
aryl
7.39 (d, J = 8.0 Hz, 2H), 7.29 (d, J =8.0 Hz, 2H), 3.58 (s, 3H), 3.52 (s,
3H), 2.44 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 198.1, 140.4,
131.9, 136.8, 128.3, 45.7, 42.0, 21.5 ppm. HRMS (ESI) m/z [M+H]+ Calcd
for C10H14NS2 (212.0562); found: 212.0567.
dimethylcarbamo(dithioperoxo)thioates could be furnished
smoothly in moderate to good yields by modulating the reaction
temperature, base, and catalyst. The protocol features easily
available starting materials, high selectivity and easy
performance, showing its practical synthetic value for the
preparation of some potential biologically or pharmaceutically
active compounds. The reaction mechanism and the related
applications of this protocol are under investigation in our
laboratory.
2-Fluorophenyl dimethylcarbamodithioate (3c)[20a]: According to TP1,
the residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give the target compound 3c 224 mg (yield:
1
52 %), a white solid. M.p.: 150-152 ℃. H NMR (400 MHz, CDCl3 ): δ =
7.55-7.46 (m, 2H), 7.27-7.20 (m, 2H), 3.56 (s, 3H), 3.53 (s, 3H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 195.0, 163.2 (d, JC-F = 249Hz), 138.6, 133.0
(d, JC-F = 9.0 Hz), 127.8 (d, JC-F = 4.0 Hz), 119.3 (d, JC-F = 17.0 Hz),
116.3 (d, JC-F = 22.0 Hz), 45.8, 42.4 ppm. 19F NMR (400 MHz, CDCl3 ): δ
= -105.5 (s, 1F). HRMS (ESI) m/z [M+H]+ Calcd for C9H11FNS2
(216.0312); found: 216.0315.
Experimental Section
General remarks: All starting materials were purchased from
commercial suppliers and used without further purification unless
otherwise stated. Yields refer to isolated compounds estimated to be
>95% pure as determined by 1H NMR and capillary GC analysis. NMR
spectra were recorded on a Bruker AM400 NMR instrument in CDCl3
using TMS as an internal standard. Chemical shifts are given in ppm, and
coupling constants (J) are given in Hz. All melting points were
determined on an RY-1G melting point instrument without correction.
High-resolution mass spectra (HRMS) were recorded on a Finnigan MAT
95Q or Finnigan 90 mass instrument (ESI). TLC was performed using
aluminum plates coated with SiO2 (Merck 60, F-254) and visualized with
UV light at 254 nm. Column chromatography was performed on silica gel
(200−300 mesh) with PE (petroleum ether)/EtOAc as an eluent.
3-Fluorophenyl dimethylcarbamodithioate (3d)[20a]: According to TP1,
the residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 5:1) to give the target compound 3d 211 mg (yield:
49 %), a pale yellow solid. M.p.: 52-56 ℃. 1H NMR (400 MHz, CDCl3 ): δ
= 7.45-7.40 (m, 1H), 7.30-7.17 (m, 3H), 3.57 (s, 3H), 3.50 (s, 3H) ppm.
13C NMR (100 MHz, CDCl3): δ = 196.4, 162.5 (d, JC-F = 247.0 Hz), 133.3,
132.7 (d, JC-F = 3.0 Hz), 130.2 (d, JC-F = 8.0 Hz), 123.9 (d, JC-F = 22.0 Hz),
117.2 (d, JC-F = 21.0 Hz), 45.7, 42.1 ppm. 19F NMR (400 MHz, CDCl3 ): δ
= -111.8 (s, 1F). HRMS (ESI) m/z [M+H]+ Calcd for C9H11FNS2
(216.0312); found: 216.0309.
Phenyl diethylcarbamodithioate (3e)[19f]: According to TP1, the residue
was purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 10:1) to give the target compound 3e 257 mg (yield: 57 %), a
pale yellow oil. 1H NMR (400 MHz, CDCl3): δ: 7.48 (d, J = 9.0 Hz, 5H),
4.06 (d, J = 6.0 Hz, 2H), 3.89 (d, J = 3.0 Hz, 2H), 1.43 (t, J = 3.0 Hz, 3H),
1.32 (t, J = 4.0 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.0,
137.1, 131.6, 130.0, 129.0, 49.9, 47.3, 12.7, 11.6 ppm. HRMS (ESI) m/z
[M+H]+ Calcd for C11H16NS2 (226.0719); found: 226.0723.
Typical procedure for the preparation of aryl dithiocarbamate (TP1):
diphenyl disulfide (1 mmol), tetraalkylthiuram disulfide (1.2 mmol), CuI
(10 mmol %) and K2CO3 (2.0 mmol) were added in a dried sealed tube
equipped with a septum and magnetic stirring bar, DMF (2.0 mL) was
then added. The mixture was stirred at 120 ℃ and checked by TLC until
the starting material was finished (about 24 h). The reaction was
quenched with sat. NH4Cl solution (3.0 mL) and then extracted with ethyl
acetate. The crude solution was dried over anhydrous Na2SO4 and
evaporated under vacuum. The residue was purified by flash column
chromatography to afford the desired product.
4-Methylphenyl diethylcarbamodithioate (3f)[19f]: According to TP1,
the residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 15:1) to give the target compound 3f 282 mg (yield:
1
59 %), a white solid. M.p.: 73-75 ℃. H NMR (400 MHz, CDCl3): δ: 7.39
(d, J = 2.0 Hz, 2 H), 7.28 (d, J = 2.0 Hz, 2H), 4.09-4.03 (m, 2H), 3.91-
3.96 (m, 2H), 2.43 (s, 3H), 1.43 (t, J = 4.0 Hz, 3H), 1.31 (t, J = 3.0 Hz,
3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.5, 140.3, 137.0, 129.9,
128.2, 49.9, 47.2, 21.5, 12.7, 11.6 ppm. HRMS (ESI) m/z [M+H]+ Calcd
for C11H18NS2 (240.0875); found: 240.0879.
Typical
procedure
for
the
preparation
of
dimethylcarbamo(dithioperoxo)thioate (TP2): diphenyl disulfide (1
mmol) and tetraalkylthiuram disulfide (1.2 mmol) were added in a dried
sealed tube equipped with a septum and magnetic stirring bar, DMF (2.0
mL) was then added. The mixture was stirred at room temperature and
checked by TLC until the starting material was finished (about 24 h). The
reaction was quenched with sat. NH4Cl solution (3.0 mL) and then
extracted with ethyl acetate. The crude solution was dried over
anhydrous Na2SO4 and evaporated under vacuum. The residue was
purified by flash column chromatography to afford the desired product.
2-Fluorophenyl diethylcarbamodithioate (3g)[18]: According to TP1,
the residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give the target compound 3g 267 mg (yield:
55 %), a yellow oil. 1H NMR (400 MHz, CDCl3 ): δ = 7.55-7.47 (m, 2H),
7.29-7.19 (m, 2H), 4.07-4.02 (, 2H), 3.93-3.88 (m, 2H), 1.45 (t, J = 4.0 Hz,
3H), 1.31 (t, J = 3.0 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 193.6,
Phenyl dimethylcarbamodithioate (3a)[19f]
: According to TP1, the
163.2 (d, JC-F = 249.0 Hz), 138.8, 133.8 (d, JC-F = 9.0 Hz), 124.6 (d, JC-F
=
residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 5:1) to give the target compound 3a 256 mg (yield:
65 %), a white solid. M.p.: 90-92 ℃. 1H NMR (400 MHz, CDCl3): δ =
4.0 Hz), 119.2 (d, JC-F = 18.0 Hz), 116.3 (d, JC-F = 22.0 Hz), 50.1, 47.1,
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12.8, 11.6 ppm. 19F NMR (400 MHz, CDCl3 ): δ = -105.3 (s, 1F). HRMS
(ESI) m/z [M+H]+ Calcd for C11H15FNS2 (244.0625); found: 244.0621.
(s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.7, 162.7 (d, JC-F
=
247.0 Hz), 138.2 (d, JC-F = 8.0 Hz), 130.2 (d, JC-F = 8.0 Hz), 124.2 (d, JC-F
= 3.0 Hz), 115.4 (d, JC-F = 24.0 Hz), 114.7 (d, JC-F = 22.0 Hz), 45.6, 41.7
ppm. Anal. calcd for C9H8Cl3FNS3: C, 32.49; H, 2.42; N, 4.21; found: C,
32.35; H, 42.58; N, 4.33%.
3-Fluorophenyl diethylcarbamodithioate (3h): According to TP1, the
residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 15:1) to give the target compound 3h 228 mg (yield:
47 %), a brown oil. 1H NMR (400 MHz, CDCl3 ): δ = 7.48-7.40 (m, 1H),
7.32-7.18 (m, 3H), 4.08-4.03 (m, 2H), 3.90-3.85 (m, 2H), 1.43 (t, J = 5.0
Hz, 3H), 1.32 (t, J = 3.0 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ =
Phenyl diethylcarbamo(dithioperoxo)thioate (4f)[17]: According to TP2,
the residue was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give the target compound 4f 329 mg (yield:
64 %), a yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.59-7.56 (m, 2H),
7.34-7.25 (m, 3H), 4.10-4.04 (m, 2H), 3.88-3.82 (m, 2 H), 1.39-1.31 (m, 6
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.2, 136.1, 128.9, 127.8,
52.0, 47.1, 13.3, 11.5 ppm. Anal. calcd for C11H15NS3: C, 51.32; H, 5.87;
N, 5.44; found: C, 51.15; H, 5.98; N, 5.35%.
194.8, 162.4 (d, JC-F = 247.0 Hz), 133.2 (d, JC-F = 8.0 Hz), 132.9 (d, JC-F
=
3.0 Hz), 130.1 (d, JC-F = 8.0 Hz), 124.1 (d, JC-F = 22.0 Hz), 117.2 (d, JC-F
= 21.0 Hz), 49.9, 47.5, 12.8, 11.6 ppm. 19F NMR (400 MHz, CDCl3 ): δ = -
120.0 (s, 1F). HRMS (ESI) m/z [M+H]+ Calcd for C11H15FNS2
(244.0625); found: 244.0627.
Phenyl dimethylcarbamo(dithioperoxo)thioate (4a)[17]: According to
TP2, the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 5:1) to give the target compound 4a 302
mg (yield: 66 %), a white solid. M.p.: 68-70 ℃. 1H NMR (400 MHz,
CDCl3): δ = 7.58-7.25 (m, 5H), 3.58 (s, 3H), 3.45 (s, 3H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 195.7, 135.9, 129.3, 128.9, 128.0, 47.5, 41.8 ppm.
Anal. calcd for C9H11NS3: C, 47.13; H, 4.83; N, 6.11; found: C, 47.01; H,
4.95; N, 6.02%.
4-Methylphenyl
diethylcarbamo(dithioperoxo)thioate
(4g)[20c]
:
According to TP2, the residue was purified by flash chromatography on
silica gel (petroleum ether/ethyl acetate = 15:1) to give the target
compound 4g 379 mg (yield: 70 %), a yellow oil. 1H NMR (400 MHz,
CDCl3 ): δ = 7.52 (d, J = 2.0 Hz, 2H), 7.13 (d, J =2.0 Hz, 2H), 4.10-4.05
(m, 2H), 3.87-3.81 (m, 2H), 2.34 (s, 3H), 1.38-1.31 (m, 6H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 194.7, 138.3, 132.7, 130.1, 129.7, 51.9,
47.1, 21.2, 13.2 11.5 ppm. Anal. calcd for C12H17NS3: C, 51.30; H, 6.31;
N, 5.16; found: C, 51.18; H, 6.42; N, 5.27%.
4-Methylphenyl
dimethylcarbamo(dithioperoxo)thioate
(4b)[20b]
:
According to TP2, the residue was purified by flash chromatography on
silica gel (petroleum ether/ethyl acetate = 5:1) to give the target
compound 4b 327 mg (yield: 67 %), a white solid. M.p.: 79-81 ℃. 1H
NMR (400 MHz, CDCl3 ): δ = 7.51 (d, J = 2.0 Hz, 2H), 7.10 (d, J =2.0 Hz,
2H), 3.56 (s, 3H), 3.41 (s, 3H), 2.31 (s, 3H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 196.0, 138.4, 132.5, 130.2, 129.7, 47.4, 41.7, 21.7 ppm. Anal.
calcd for C10H13NS3: C, 49.35; H, 5.38; N, 5.75; found: C, 49.21; H, 5.47;
N, 5.68%.
2-Fluorophenyl diethylcarbamo(dithioperoxo)thioate (4h): According
to TP2, the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) to give the target compound 4h
303 mg (yield: 55 %), a yellow oil. H NMR (400 MHz, CDCl3 ): δ = 7.66-
7.64 (m, 1H), 7.27-7.24 (m, 1H), 7.14-7.04 (m, 2H), 4.08-4.02 (m, 2H),
3.87-3.82 (m, 2H), 1.38-1.30 (m, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ
1
= 193.5, 160.5 (d, JC-F = 245 Hz), 132.7 (d, JC-F = 1.0 Hz), 129.8 (d, JC-F
=
8.0 Hz), 124.5 (d, JC-F = 4.0 Hz), 123.0 (d, JC-F = 17.0 Hz), 115.6 (d, JC-F
= 22.0 Hz), 51.9, 47.7, 13.3, 11.4 ppm. 19F NMR (400 MHz, CDCl3 ): δ = -
105.5 (s, 1F). Anal. calcd for C11H14FNS3: C, 47.97; H, 5.12; N, 5.09;
found: C, 47.85; H, 5.25; N, 4.98%.
2-Fluorophenyl
dimethylcarbamo(dithioperoxo)thioate
(4c):
According to TP2, the residue was purified by flash chromatography on
silica gel (petroleum ether/ethyl acetate = 10:1) to give the target
compound 4c 361 mg (yield: 73 %), a yellow solid. M.p.: 50-52 ℃. 1H
NMR (400 MHz, CDCl3 ): δ = 7.69-7.53 (m, 1H), 7.27-7.25 (m, 1H), 7.14-
7.03 (m, 2H), 3.59 (s, 3H), 3.47 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 195.0, 160.6 (d, JC-F = 246 Hz), 132.0 (d, JC-F = 1.0 Hz), 130.0 (d, JC-F
= 7.0 Hz), 124.5 (d, JC-F = 4.0 Hz), 122.7, 115.6 (d, JC-F = 21.0 Hz), 47.4,
41.7 ppm. 19F NMR (400 MHz, CDCl3 ): δ = -109.9 (s, 1F). Anal. calcd
for C9H10NS3: C, 43.70; H, 4.07; N, 5.66; found: C, 43.54; H, 4.19; N,
5.55%.
2,4,5-Trichlorophenyl
diethylcarbamo(dithioperoxo)thioate
(4i):
According to TP2, the residue was purified by flash chromatography on
silica gel (petroleum ether/ethyl acetate = 10:1) to give the target
compound 4i 373 mg (yield: 52 %), a white solid. M.p.: 68-72 ℃. 1H NMR
(400 MHz, CDCl3 ): δ = 7.50 (s, 1H), 7.43 (s, 1H), 4.03 (s, 2H), 3.87 (s,
2H), 1.40 (s, 3H), 1.30 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ =
191.2, 135.1, 131.7, 131.4, 130.9, 130.5, 129.3, 52.2, 47.5, 13.5, 11.4
ppm. Anal. calcd for C11H12Cl3NS3: C, 36.62; H, 3.35; N, 3.88; found: C,
36.48; H, 3.46; N, 3.96%.
3-Fluorophenyl
dimethylcarbamo(dithioperoxo)thioate
(4d):
According to TP2, the residue was purified by flash chromatography on
silica gel (petroleum ether/ethyl acetate = 5:1) to give the target
compound 4d 371 mg (yield: 75 %), a yellow oil. 1H NMR (400 MHz,
CDCl3 ): δ = 7.31-7.24 (m, 3H), 6.95-6.90 (m, 1H), 3.58 (s, 3H), 3.47 (s,
3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.7, 162.7 (d, JC-F = 247.0
Hz), 138.2 (d, JC-F = 8.0 Hz), 130.2 (d, JC-F = 8.0 Hz), 124.2 (d, JC-F = 3.0
Hz), 115.4 (d, JC-F = 24.0 Hz), 114.7 (d, JC-F = 22.0 Hz), 45.6, 41.7 ppm.
19F NMR (400 MHz, CDCl3 ): δ = -111.1 (s, 1F). Anal. calcd for
C9H10FNS3: C, 43.70; H, 4.07; N, 5.66; found: C, 43.51; H, 4.19; N,
5.72%.
Acknowledgments
The foundation support from National Natural Science
Foundation of China (21302150), Hubei Provincial Science and
Technology (2019CFB596), Chen-Guang program from Hubei
Association for Science and Technology, Ministry-of-Education
Key Laboratory for the Synthesis and Application of Organic
Functional Molecules, Hubei University (KLSAOFM1810) are all
greatly appreciated. K. P. thanks the support of Postgraduate
Innovation Foundation from Wuhan Institute of Technology.
2,4,5-Trichlorophenyl dimethylcarbamo(dithioperoxo)thioate (4e):
According to TP2, the residue was purified by flash chromatography on
silica gel (petroleum ether/ethyl acetate = 10:1) to give the target
compound 4e 351 mg (yield: 53 %), a white solid. M.p.: 150-154 ℃. 1H
NMR (400 MHz, CDCl3 ): δ = 7.57 (s, 1H), 7.48 (s, 1H), 3.64 (s, 3H), 3.57
Keywords: dithiocarbamates
selective synthesis • C-S/S-S formation
• tetraalkylthiuram disulfide •
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10.1002/ejoc.201901401
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Key Topic*
Author(s), Corresponding Author(s)*
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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
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Key Topic*: Chemo-selective C-S/S-S
Formation
Kang Peng, Hui Zhu, Xing Liu, Han-Ying
Peng, Jin-Quan Chen, and Zhi-Bing
Dong *
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Chemo-selective C-S/S-S Formation
between Diphenyl Disulfides and
Tetraalkylthiuram Disulfides
*one or two words that highlight the emphasis of the paper or the field of the study
An efficient C-S/S-S formation for the chemo-selective synthesis of aryl dithiocarbamate (C-S formation) and aryl
dialkylcarbamo(dithioperoxo)thioate (S-S formation) was studied. The chemo-selectivity could be controlled by modulating the
reaction temperature, base, and catalyst. The transformation features simple performance, easily available starting material,
high selectivity and easy performance, showing its practical synthetic value for the preparation of some potential biologically
or pharmaceutically active compounds.
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