Transition-Metal-Free C(sp3)–S Coupling in Water: Synthesis of Benzyl Dithiocarbamates Using Thiuram Disulfides as an Organosulfur Source

Article abstract of DOI:10.1002/ejoc.201801520

A simple, highly efficient and environmentally benign method for the synthesis of benzyl dithiocarbamates was reported. Without addition of metal catalyst, a series of 34 benzyl dithiocarbamates were obtained in good to excellent yields by treating benzyl halides with tetraalkylthiuram disulfides in water. The protocol allows easy access to C(sp³)–S bond formation, features the advantages of easy performance, environmental friendliness, good to excellent yields, and good functional tolerance, showing potential value for the preparation of some biologically active compounds.

Full text of DOI:10.1002/ejoc.201801520

A Journal of
Accepted Article
Title: Transition-metal-free C(sp3)−S coupling in water: synthesis of
benzyl dithiocarbamates using thiuram disulfides as organosulfur
source
Authors: Han-Ying Peng and Zhi-Bing Dong
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801520
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801520
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Transition-metal-free C(sp3)−S coupling in water: synthesis of
benzyl dithiocarbamates using thiuram disulfides as organosulfur
source
Han-Ying Peng[a] and Zhi-Bing Dong*[a][b]
Abstract: A simple, highly efficient and environmentally benign
method for the synthesis of benzyl dithiocarbamates was reported.
Without addition of metal catalyst, series of 34 benzyl
Generally, a portion of these compounds are prepared through
the reactions of benzyl halides, amines, and carbon disulfide.[8-11]
Some methods for their synthesis involve the reaction of benzyl
alcohols and dithiocarbamates.[12-14] There are also reactions in
a
dithiocarbamates were obtained in good to excellent yields by
treating benzyl halides with tetraalkylthiuram disulfides in water. The
protocol allows easy access to C(sp3)-S bond formation, features the
advantages of easy performance, environmental friendliness, good
to excellent yields, and good functional tolerance, showing potential
value for the preparation of some biologically active compounds
which benzaldehydes or organometallic reagents are used
16]
(Figure 2).[15,
However, these methods require using large
amounts of organic solvents, toxic and foul smelling reagents, or
organometallic reagents sensitivity to air and moisture, which
limit their application in pharmaceutical synthesis.
Introduction
Benzyl dithiocarbamates are important molecules in organic
chemistry. They play an important role in the pharmaceutical
synthesis.[1] Benzyl dithiocarbamates containing tetrazole blocks
are universal in medicinal molecules which are used for treating
cardiovascular diseases.[2] They are likewise necessary
intermediates for the synthesis of anticoagulants.[3] In addition,
studies have shown that benzyl dithiocarbamates have
biological activity.[4] They are useful as radiolabelling reagents
which contain the 11C isotope.[5] Furthermoere, benzyl
dithiocarbamates could be applied in material modified flame
retardant after polymerization,[6] and their diazo salts can be
used for nanocomposites synthesis (Figure 1).[7] Therefore, the
study of the preparation of these important molecules has
attracted much attention in the last decades.
Figure 2. Existing strategies towards the synthesis of benzyl dithiocarbamates.
Over the past decades, organic green synthesis has developed
rapidly,[17] and organic reactions in water have attracted much
attention. Among these, several methods are available for the
synthesis of benzyl dithiocarbamates in water, but they still have
some drawbacks, such as long reaction time, and use of
ultrasound irradiation that limit their utility and applicability.[18, 19]
Thus, more convenient and practical synthetic methods for these
important compounds are still highly desirable. As part of our
longstanding focus on developing dithiocarbamates (mostly on
the C(sp2)-S bond formation)[20] and relevant applications,[21] as
well as our efforts on organic reactions in water,[22] we hereby
wish to report an efficient and practical method for the easy
synthesis of benzyl dithiocarbamates by treating cheap and
environmentally benign tetraalkylthiuram disulfides with
substituted benzyl halides in water.
Results and Discussion
Initially, benzyl chloride and tetramethylthiuram disulfide (TMTD)
were chosen as model substrates for the reaction in water, and
the results are summarized in Table 1. At the outset, the
reaction occured in water to give the desired product 3a in 31%
yield. Thus 10 mol% of phase transfer catalyst (PTC), such as
TEAB (tetraethylammonium bromide) was added to improve the
yield (entries 1-2), however, the yield of 3a did not improve
much. The reaction temperature screening showed that 100 °C
was the optimal (entries 2-5). Gratifyingly, the yield of 3a
Figure 1. Applications of benzyl dithiocarbamates.
[a]
[b]
School of Chemistry and Environmental Engineering, Wuhan
Institute of Technology, Wuhan 430205, China.
E-mail: dzb04982@wit.edu.cn
http://cee.wit.edu.cn/info/1052/1538.htm
Department of Chemistry, Ludwig-Maximilians-Universität,
Butenandtstrasse 5-13, 81377 München, Germany.
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increased significantly when base was added to the reaction
system (entry 6). Thus, different bases were screened and
K2CO3 was chosen as the best one (entries 6-8). To our delight,
(entries 12-13). For the electron-donating methyl and methoxyl
groups, good yields were obtained (entries 5, 10). When 2-
methylbenzyl bromide 1k was used, product 3k was obtained in
3a was obtained in good yield (entry 9) even without adding PTC, 84% yield (entry 11). It is noteworthy that 1-chloromethyl
which demonstrated that the PTC was not crucial for the model
reaction (entries 9-10). The optimal reaction conditions were
summarized in entry 9 and the subsequent control experiments
(entries 11-12) revealed that 100 °C was the most suitable
temperature for benzyl bromide. In addition, an experiment on a
20 mmol scale gave 3a in 70% yield, showing the efficiency of
this protocol in the potential application in industry.
naphthalene 1n was also suitable to react with TMTD, giving
product 3n with excellent yield (93%, entry 14). Subsequently,
substituted benzyl halides were reacted with tetraethylthiuram
disulfide (TETD) under the standard reaction conditions. As for
benzyl bromides, substituents ranging from weak electron-
withdrawing groups, such as Br and methyl ester, to strong
electron-withdrawing groups, such as NO2, along with electron-
donating methoxyl groups, all furnished the desired benzyl
diethyldithiocarbamates in good yields (entries 15-20). Due to
the possible low reactivity of benzyl chloride, compounds 3u-3zb
were obtained in moderate yields (entries 21-28). As expected,
some electron-withdrawing group such as F and CN gave
slightly lower yields (entries 26, 27), while substrate 2-
methylbenzyl bromide gave a higher yield (entry 25). Similarly,
tetrabutylthiuram disulfide (TBTD) was also tested and the
desired products were successfully obtained in good yields
(entries 29-33). For 1-chloromethyl group, the isolation yield of
product 3zh was 49% (entry 34). It is worthy to note that ester
groups could be tolerated well, giving the desired products in
good to excellent yields (entries 6, 20, 33).
Table 1. Optimization of the reaction conditions for the model reactiona
Entry
1
1a
PTC
Base
Temp (°C)
80
Yieldb (%)
31
X=Cl
X=Cl
X=Cl
X=Cl
X=Cl
X=Cl
X=Cl
X=Cl
X=Cl
X=Cl
X=Br
X=Br
-
-
-
2
TEAB
80
46
3
TEAB
-
100
120
120
100
100
100
100
100
100
80
54
Table 2. Synthesis of benzyl dithiocarbamate starting from substituted benzyl
halides and tetraalkylthiuram disulfides (TMTD, TETD and TBTD)a
4
TEAB
-
53
5
-
-
53
6
TEAB
K2CO3
Cs2CO3
KOH
K2CO3
Cs2CO3
K2CO3
K2CO3
70
7
TEAB
68
8
TEAB
57
Entry
1
Benzyl halide
thiuram
reagent
product
Yieldb
(%)
9
-
-
-
-
72/70c
71
10
11
12
84
2a
2a
84
1a
1b
3a
68
2
3
4
85
[a] Reaction conditions: benzyl chloride (1.0 mmol), tetramethylthiuram
disulfide (1.0 mmol), PTC (10% eq.), base (1.0 eq.) and H2O as solvent (2.0
mL), stirred for 3 h. [b] Isolated yields based on benzyl halide after column
chromatography.[c] Performed on a 20 mmol scale.
3b
3c
With the above mentioned optimized conditions in hand, we
conducted the investigation by reacting tetraalkylthiuram
disulfides with different benzyl halides, and the results are
summarized in Table 2. As for tetramethylthiuram disulfide
(TMTD), the reaction activity of benzyl bromide is better than
benzyl chloride (entries 1, 7). In general, substituents ranging
from weak electron-withdrawing groups, such as Cl, Br and
methyl ester, to strong electron-withdrawing groups, such as
NO2, all generated the corresponding benzyl dithiocarbamates in
satisfactory yields (entries 2-4, 6, 8, 9). Some electron-
withdrawing groups such as F and CN gave slightly lower yields
87
90
2a
2a
1c
1d
3d
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5
79
89
16
17
92
2a
2b
2b
1e
1b
3e
3p
6
90
2a
1f
3q
1c
1d
3f
18
19
20
94
7
72
88
2b
2b
2b
2a
3r
1g
3g
80
8
2a
1e
1f
3s
3h
3i
1h
90
9
80
2a
1i
3t
21
22
45
10
69
84
66
2b
2b
2a
1g
3u
1j
3j
69
11
2a
3v
1h
1i
1k
3k
23
24
25
26
65
12
2b
2b
2b
2b
2a
3w
1l
3l
44
13
69
93
84
2a
3x
1j
1m
3m
3n
69
14
3y
2a
1k
1l
1n
48
15
2b
3z
1a
3o
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27
51
77
69
83
84
products could be obtained in good to excellent yields. The
protocol features advantages including experimental simplicity,
water as solvent, transition-metal-free, good functional
compatibility, and good to excellent yields, illustrating its
potential synthetic value in the convenient preparation of some
potential biologically active compounds.
2b
1m
3za
3zb
3zc
3zd
28
2b
1n
29
Experimental Section
Gerneral 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%
2c
1a
1
pure as determined by H 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 a
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 eluent.
30
2c
1b
31
2c
Typical procedure for the preparation of benzyl dithiocarbamate:
Benzyl halide (1; 1.0 mmol), tetraalkylthiuram disulfide (2; 1.0 mmol), and
K2CO3 (1.0 mmol) were added to a dried sealed tube equipped with a
septum and magnetic stirring bar. H2O (2 mL) was then added. The
mixture was stirred at 100 °C, and the reaction progress was checked by
TLC until the starting material had been completely consumed (benzyl
bromide: 0.5 h, benzyl chloride: 3 h). The mixture was then cooled to
room temperature, quenched with satd. NH4Cl solution (5 mL), and then
extracted with ethyl acetate. The organic phase was dried with
anhydrous Na2SO4, and the solvents were evaporated under vacuum.
The residue was purified by flash column chromatography to give the
desired product.
3ze
3zf
1c
32
87
74
2c
1d
33
2c
1f
3zg
3zh
Benzyl dimethylcarbamodithioate (3a): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 10:1) to give compound 3a (84 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.42 (d, J=8.0 Hz, 2H) 7.37-7.25 (m,
3H), 4.59 (s, 2H), 3.57 (s, 3H), 3.35 (s, 3H) ppm. 13C NMR (100
MHz, CDCl3): δ = 196.7, 136.2, 129.3, 128.6, 127.5, 45.4, 42.6,
41.4 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C10H14NS2 212.0562;
found 212.0564.
34
2c
1n
49
[a] Reaction conditions: benzyl halide (1.0 mmol), tetraalkylthiuram disulfide
(1.0 mmol), H2O (2.0 mL), heated at 100 oC for 0.5-3 h (0.5 h for benzyl
bromide, 3 h for benzyl chloride). [b] Isolated yields.
4-Bromobenzyl dimethylcarbamodithioate (3b): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3b (85 %) as a white
solid. m.p. 65-67 °C. 1H NMR (400 MHz, CDCl3): δ = 7.48-7.39 (m,
2H), 7.28 (d, J=8.0 Hz, 2H), 4.52 (s, 2H), 3.55 (s, 3H), 3.35 (s, 3H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 196.2, 135.7, 131.6, 131.0,
121.3, 45.5, 41.6, 41.5 ppm. HRMS (ESI) m/z [M+H]+ Calcd for
C10H13BrNS2 289.9668; found 289.9674.
The proposed reaction pathway is the SN2 process. Firstly,
the cleavage of the S-S bond yields a dithiocarbamte anion,
which is ready to react as nucleopile with the benzyl halide;
secondly,
the
dithiocarbamte
anion
attacks
benzyl
dithiocarbamate via SN2 manner to give the desired product and
dithiocarbamate halide as byproduct which is easily
decomposed in the work-up step under basic conditions.
Conclusions
2-Bromobenzyl dimethylcarbamodithioate (3c): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3c (87 %) as a white
solid. m.p. 62-64 °C. 1H NMR (400 MHz, CDCl3): δ = 7.63-7.50 (m,
In summary, we have developed a simple, highly efficient
method for the synthesis of benzyl dithiocarbamates. By the
treatment of benzyl halides with tetraalkylthiuram disulfides
(TMTD, TETD and TBTD), the desired C(sp3)-S coupling
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2H), 7.25 (t, J=8.0 Hz, 1H), 7.12 (t, J=8.0 Hz, 1H), 4.71 (s, 2H), 3.52
(s, 3H), 3.32 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.2,
136.2, 132.9, 131.6, 129.4, 127.7, 125.0, 45.7, 42.7, 41.6 ppm.
HRMS (ESI) m/z [M+H]+ Calcd for C10H13BrNS2 289.9668; found
289.9663.
ppm. 13C NMR (100 MHz, CDCl3): δ = 196.3, 135.1, 133.2, 130.7,
128.7, 45.5, 41.6, 41,4 ppm. HRMS (ESI) m/z [M+H]+ Calcd for
C10H13ClNS2 246.0173; found 246.0176.
4-Methylbenzyl dimethylcarbamodithioate (3j): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3j (69 %) as a white
4-Nitrobenzyl dimethylcarbamodithioate (3d): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 10:1) to give compound 3d (90 %) as a yellow solid. m.p.
105-107 °C. 1H NMR (400 MHz, CDCl3): δ = 8.20-8.14 (m, 2H), 7.59
(d, J=8.0 Hz, 2H), 4.70 (s, 2H), 3.59 (s, 3H), 3.40 (s, 3H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 196.5, 147.2, 144.9, 130.1, 123.7, 45.8,
41.5, 41.0 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C10H13N2O2S2
257.0413; found 257.0411.
1
solid. m.p. 49-51 °C. H NMR (400 MHz, CDCl3): δ = 7.31 (d,
J=8.00 Hz, 2H), 7.15 (d, J=8.0 Hz, 2H), 4.54 (s, 2H), 3.58 (s, 3H),
3.36 (s, 3H), 2.36 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ =
197.0, 137.2, 132.9, 129.3, 129.2, 45.3, 42.5, 41.4, 21.2 ppm.
HRMS (ESI) m/z [M+H]+ Calcd for C11H16NS2 226.0719; found
226.0716.
2-Methylbenzyl dimethylcarbamodithioate (3k): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3k (84 %) as a white
solid. m.p. 94-96 °C. 1H NMR (400 MHz, CDCl3): δ = 7.39 (d, J=8.0
Hz, 1H), 7.27-7.13 (m, 3H), 4.54 (s, 2H), 3.59 (s, 3H), 3.35 (s, 3H),
2.43 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 197.0, 137.4,
133.4, 130.5, 130.4, 128.0, 126.3, 45.2, 41.4, 41.3, 19.4 ppm.
HRMS (ESI) m/z [M+H]+ Calcd for C11H16NS2 226.0719; found
226.0717.
3-Methoxybenzyl dimethylcarbamodithioate (3e): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3e (79 %) as a yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 7.25 (t, J=8.0 Hz, 1H), 6.98 (t,
J=8.0 Hz, 2H), 6.88-6.78 (m, 1H), 4.55 (s, 2H), 3.82 (s, 3H), 3.58 (s,
3H), 3.37 (3, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.8,
159.7, 137.7, 129.6 121.6, 114.8, 113.2, 55.2, 45.4, 42.6, 41.4 ppm.
HRMS (ESI) m/z [M+H]+ Calcd for C11H16NOS2 242.0668; found
242.0661.
4-Fluorobenzyl dimethylcarbamodithioate (3l): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3l (66 %) as a yellow
solid. m.p. 47-49 °C. 1H NMR (400 MHz, CDCl3): δ = 7.43-7.32 (m,
2H), 7.07-6.95 (m, 2H), 4.55 (s, 2H), 3.57 (s, 3H), 3.36 (s, 3H) ppm.
13C NMR (100 MHz, CDCl3): δ = 196.5, 162.1 (d, J=245.0 Hz),
132.2 (d, J=4.0 Hz), 131.0 (d, J=9.0 Hz), 115.4 (d, J=21.0 Hz), 45.4,
41.6, 41.4 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C10H13FNS2
230.0468; found 230.0466.
Methyl 4-(((dimethylcarbamothioyl)thio)methyl)benzoate (3f):
The synthesis was carried out according to the typical procedure,
and the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) to give compound 3f (89 %)
as a yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J=8.0 Hz,
2H), 7.46 (d, J=8.0 Hz, 2H), 4.62 (s, 2H), 3.90 (s, 3H), 3.56 (s, 3H),
3.36 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.1, 166.8,
142.0, 129.8, 129.3, 129.2, 52.1, 45.6, 41.9, 41.4 ppm. HRMS (ESI)
m/z [M+H]+ Calcd for C12H16NO2S2 270.0617; found 270.0621.
Benzyl dimethylcarbamodithioate (3g): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
4-Cyanobenzyl dimethylcarbamodithioate (3m): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3m (69 %) as a white
solid. m.p. 112-114 °C. 1H NMR (400 MHz, CDCl3): δ = 7.60 (d,
J=8.0 Hz, 2H), 7.52 (d, J=8.0 Hz, 2H), 4.64 (s, 2H), 3.58 (s, 3H),
3.39 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.6, 142.7,
132.2, 130.0, 118.8, 111.1, 45.7, 41.5, 41.4 ppm. HRMS (ESI) m/z
[M+H]+ Calcd for C11H13N2S2 237.0515; found 237.0518.
1
acetate = 10:1) to give compound 3g (72 %) as a yellow oil. H
NMR (400 MHz, CDCl3): δ = 7.42 (d, J=8.0 Hz, 2H), 7.35-7.07 (m,
3H), 4.60 (s, 2H), 3.58 (s, 3H), 3.36 (s, 3H) ppm. 13C NMR (100
MHz, CDCl3): δ = 196.8, 136.2, 129.3, 128.6, 127.5, 45.4, 42.6,
41.4 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C10H14NS2 212.0562;
found 212.0563.
2-Chlorobenzyl dimethylcarbamodithioate (3h): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3h (88 %) as a white
solid. m.p. 72-74 °C. 1H NMR (400 MHz, CDCl3): δ = 7.63-7.55 (m,
1H), 7.42-7.35 (m, 1H), 7.26-7.18 (m, 2H), 4.72 (s, 2H), 3.57 (s, 3H),
3.36 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.5, 134.5,
134.4, 131.5, 129.6, 129.0, 127.0, 45.5, 41.4, 40.1 ppm. HRMS
(ESI) m/z [M+H]+ Calcd for C10H13ClNS2 246.0173; found 246.0174.
Naphthalen-1-ylmethyl dimethylcarbamodithioate (3n): The
synthesis was carried out according to the typical procedure, and
the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 100:1) to give compound 3n (93 %)
as a yellow oil. 1H NMR (400 MHz, CDCl3): δ = 8.15 (d, J=8.0 Hz,
1H), 7.90 (d, J=8.0 Hz, 1H), 7.84 (d, J=12.00 Hz, 1H), 7.67-7.51 (m,
3H), 7.45 (t, J=8.00 Hz, 1H), 5.06 (s, 2H), 3.57 (s, 3H), 3.24 (s, 3H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 196.7, 133.9, 131.9, 131.5,
128.9, 128.7, 128.3, 126.5, 126.1, 125.6, 124.1, 45.3, 41.4, 41.0
ppm. HRMS (ESI) m/z [M+H]+ Calcd for C14H16NS2 262.0719; found
262.0724.
4-Chlorobenzyl dimethylcarbamodithioate (3i): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) to give compound 3i (80 %) as a white
solid. m.p. 54-56 °C. 1H NMR (400 MHz, CDCl3): δ = 7.34 (d, J=8.0
Hz, 2H), 7.31-7.24 (m, 2H), 4.54 (s, 2H), 3.56 (s, 3H), 3.36 (s, 3H)
Benzyl diethylcarbamodithioate (3o): The synthesis was carried
out according to the typical procedure, and the residue was purified
by flash chromatography on silica gel (petroleum ether/ethyl acetate
= 100:1) to give compound 3o (84 %) as a yellow oil. 1H NMR (400
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MHz, CDCl3): δ = 7.42 (d, J=8.0 Hz, 2H), 7.38-7.25 (m, 3H), 4.58 (s,
2H), 4.15-3.99 (m, 2H), 3.83-3.68 (m, 2H), 1.36-1.27 (m, 6H) ppm.
13C NMR (100 MHz, CDCl3): δ = 195.3, 136.1, 129.4, 128.6, 127.5,
49.5, 46.8, 42.2, 12.5, 11.6 ppm. HRMS (ESI) m/z [M+H]+ Calcd for
C12H18NS2 240.0875; found 240.0874.
by flash chromatography on silica gel (petroleum ether/ethyl acetate
= 100:1) to give compound 3u (45 %) as a yellow oil. 1H NMR (400
MHz, CDCl3): δ = 7.42 (d, J=8.0 Hz, 2H), 7.38-7.25 (m, 3H), 4.58 (s,
2H), 4.17-3.98 (m, 2H), 3.86-3.65 (m, 2H), 1.37-1.25 (m, 6H) ppm.
13C NMR (100 MHz, CDCl3): δ = 195.3, 136.1, 129.4, 128.6, 127.5,
49.5, 46.8, 42.2, 12.5, 11.6 ppm. HRMS (ESI) m/z [M+H]+ Calcd for
C12H18NS2 240.0875; found 240.0872.
4-Bromobenzyl diethylcarbamodithioate (3p): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3p (92 %) as a yellow solid. m.p.
50-52 °C. 1H NMR (400 MHz, CDCl3): δ = 7.44 (d, J=8.0 Hz, 2H),
7.28 (d, J=8.0 Hz, 2H), 4.53 (s, 2H), 4.12-3.99 (m, 2H), 3.83-3.65
(m, 2H), 1.29 (t, J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 194.7, 135.6, 131.6, 131.0, 121.3, 49.7, 46.8, 41.2, 12.6, 11.6
ppm. HRMS (ESI) m/z [M+H]+ Calcd for C12H17BrNS2 317.9981;
found 317.9985.
2-Chlorobenzyl diethylcarbamodithioate (3v): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3v (69 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.61-7.54 (m, 1H), 7.42-7.34 (m, 1H),
7.27-7.18 (m, 2H), 4.72 (s, 2H), 4.12-3.99 (m, 2H), 3.83-3.66 (m,
2H), 1.29 (t, J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ =
194.9, 134.5, 134.4, 131.6, 129.5, 128.9, 127.0, 49.7, 46.8, 39.6,
12.6, 11.6 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C12H17ClNS2
274.0486; found 274.0485.
2-Bromobenzyl diethylcarbamodithioate (3q): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3q (90 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.58 (t, J=8.0 Hz, 2H), 7.28 (t, J=8.0
Hz, 1H), 7.14 (t, J=8.00 Hz, 1H), 4.73 (s, 2H), 4.13-3.99 (m, 2H),
3.82-3.69 (m, 2H), 1.30 (t, J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 194.9, 136.2, 132.9, 131.6, 129.1, 127.6, 125.0, 49.7,
46.8, 42.2, 12.5, 11.6 ppm. HRMS (ESI) m/z [M+H]+ Calcd for
C12H17BrNS2 317.9981; found 317.9979.
4-Chlorobenzyl diethylcarbamodithioate (3w): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 100:1) to give compound 3w (65 %) as a
yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.34 (d, J=8.0 Hz, 2H),
7.28 (d, J=8.0 Hz, 2H), 4.54 (s, 2H), 4.15-3.96 (m, 2H), 3.84-3.64
(m, 2H), 1.29 (t, J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 194.7, 135.1, 133.2, 130.7, 128.7, 49.7, 46.8, 41.2, 12.6, 11.6
ppm. HRMS (ESI) m/z [M+H]+ Calcd for C12H17ClNS2 274.0486;
found 274.0488.
4-Nitrobenzyl diethylcarbamodithioate (3r): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3r (94 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 8.17 (d, J=8.0 Hz, 2H), 7.58 (d, J=8.0
Hz, 2H), 4.70 (s, 2H), 4.11-3.99 (m, 2H), 3.83-3.70 (m, 2H), 1.31 (t,
J=8.00 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ = 193.9, 147.1,
145.0, 130.1, 123.7, 50.0, 46.9, 40.6, 12.6, 11.5 ppm. HRMS (ESI)
m/z [M+H]+ Calcd for C12H17N2O2S2 285.0726; found 285.0720.
4-Methylbenzyl diethylcarbamodithioate (3x): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3x (44 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.32 (d, J=8.0 Hz, 2H), 7.16 (d, J=8.0
Hz, 2H), 4.55 (s, 2H), 4.08 (d, J=8.0 Hz, 2H), 3.76 (d, J=4.00 Hz,
2H), 2.37 (s, 3H) 1.32 (d, J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 195.4, 137.2, 132.9, 129.4, 129.3, 49.4, 46.8, 42.1, 21.2,
12.6, 11.7 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C13H20NS2
254.1032; found 254.1039.
3-Methoxybenzyl diethylcarbamodithioate (3s): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 100:1) to give compound 3s (80 %) as a
yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.23 (t, J=8.0 Hz, 1H),
6.99 (d, J=4.00 Hz, 2H), 6.81 (d, J=8.0 Hz, 1H), 4.55 (s, 2H), 4.12-
3.99 (m, 2H), 3.79 (s, 3H), 3.77-3.66 (m, 2H), 1.29 (d, J=4.00 Hz,
6H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.1, 159.7, 137.7,
129.6, 121.7, 114.9, 113.1, 55.2, 49.5, 46.8, 42.2, 12.6, 11.7 ppm.
HRMS (ESI) m/z [M+H]+ Calcd for C13H20NOS2 270.0981; found
270.0982.
2-Methylbenzyl diethylcarbamodithioate (3y): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3y (69 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.39 (d, J=8.0 Hz, 1H), 7.26-7.15 (m,
3H), 4.54 (s, 2H), 4.18-3.92 (m, 2H), 3.88-3.60 (m, 2H), 2.43 (s, 3H),
1.37-1.25 (m, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.5,
137.4, 133.4, 130.6, 130.5, 127.9, 126.2, 49.3, 46.7, 40.9, 19.4,
12.5, 11.7 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C13H20NS2
254.1032; found 254.1029.
Methyl 4-(((diethylcarbamothioyl)thio)methyl)benzoate (3t): The
synthesis was carried out according to the typical procedure, and
the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 100:1) to give compound 3t (90 %)
as a yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J=8.0 Hz,
2H), 7.45 (d, J=8.0 Hz, 2H), 4.60 (s, 2H), 4.03 (d, J=8.00 Hz, 2H),
4-Fluorobenzyl diethylcarbamodithioate (3z): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3z (48 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.43-7.33 (m, 2H), 7.01 (t, J=8.0 Hz,
2H), 4.55 (s, 2H), 4.15-3.98 (m, 2H), 3.84-3.66 (m, 2H), 1.30 (t,
J=8.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.0, 162.1
(d, J=245.0 Hz), 132.1 (d, J=3.0 Hz), 131.0 (d, J=8.0 Hz), 115.4 (d,
J=21.0 Hz), 49.6, 46.8, 41.2, 12.5, 11.6 ppm. HRMS (ESI) m/z
[M+H]+ Calcd for C12H17FNS2 258.0781; found 258.0778.
3.89 (s, 3H), 3.72 (d, J=8.0 Hz, 2H), 1.27 (t, J=8.0 Hz, 6H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 194.5, 166.8, 142.1, 129.8, 129.3,
129.1, 52.1, 49.8, 46.8, 41.4, 12.5, 11.6 ppm. HRMS (ESI) m/z
[M+H]+ Calcd for C14H20NO2S2 298.0930; found 298.0933.
Benzyl diethylcarbamodithioate (3u): The synthesis was carried
out according to the typical procedure, and the residue was purified
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10.1002/ejoc.201801520
European Journal of Organic Chemistry
FULL PAPER
4-Cyanobenzyl diethylcarbamodithioate (3za): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 100:1) to give compound 3za (51 %) as a
yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.61 (d, J=8.0 Hz, 2H),
7.52 (d, J=8.0 Hz, 2H), 4.65 (s, 2H), 4.12-3.99 (m, 2H), 3.83-3.69
(m, 2H), 1.31 (t, J=8.00 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 194.0, 142.8, 132.2, 130.0, 118.8, 111.1, 50.0, 46.9, 41.0, 12.6,
11.5 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C13H17N2S2 265.0828;
found 265.0826.
1.79-1.66 (m, 4H), 1.44-1.33 (m, 4H), 0.98 (t, J=8.0 Hz, 6H) ppm.
13C NMR (100 MHz, CDCl3): δ = 194.2, 147.2, 145.0, 130.1, 123.6,
55.6, 52.6, 40.7, 29.7, 29.5, 28.4, 20.1, 13.8, 13.7 ppm. HRMS (ESI)
m/z [M+H]+ Calcd for C16H25N2O2S2 341.1352; found 341.1355.
Methyl 4-(((dibutylcarbamothioyl)thio)methyl)benzoate (3zg):
The synthesis was carried out according to the typical procedure,
and the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 100:1) to give compound 3zg
1
(74 %) as a yellow oil. H NMR (400 MHz, CDCl3): δ = 7.99 (d,
J=8.0 Hz, 2H), 7.47 (d, J=8.0 Hz, 2H), 4.63 (s, 2H), 3.98 (t, J=8.0
Hz, 2H), 3.92 (s, 3H), 3.66 (t, J=8.0 Hz, 2H), 1.78-1.64 (m, 4H),
1.43-1.30 (m, 4H), 1.01-0.92 (m, 6H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 194.9, 166.8, 142.1, 129.8, 129.3, 129.2, 55.3, 52.6,
52.1, 41.6, 29.4, 28.4, 20.2, 20.1, 13.8, 13.7 ppm. HRMS (ESI) m/z
[M+H]+ Calcd for C18H28NO2S2 354.1556; found 354.1551.
Naphthalen-1-ylmethyl diethylcarbamodithioate (3zb): The
synthesis was carried out according to the typical procedure, and
the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 100:1) to give compound 3zb
(77 %) as a white solid. m.p. 71-73 °C. 1H NMR (400 MHz, CDCl3):
δ = 8.15 (d, J=8.0 Hz, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.84 (d, J=8.0 Hz,
1H), 7.67-7.51 (m, 3H), 7.45 (t, J=8.0 Hz, 1H), 5.04 (s, 2H), 4.21-
4.01 (m, 2H), 3.82-3.63 (m, 2H), 1.35 (t, J=8.0 Hz, 3H), 1.25 (t,
J=8.0 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.3, 133.9,
132.0, 131.5, 128.8, 128.7, 128.3, 126.4, 126.0, 125.5, 124.1, 49.4,
46.8, 40.5, 12.5, 11.7 ppm. HRMS (ESI) m/z [M+H]+ Calcd for
C16H20NS2 290.1032; found 290.1026.
Naphthalen-1-ylmethyl dibutylcarbamodithioate (3zh): The
synthesis was carried out according to the typical procedure, and
the residue was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate = 100:1) to give compound 3zh
1
(49 %) as a yellow oil. H NMR (400 MHz, CDCl3): δ = 8.14 (d,
J=8.0 Hz, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.65-
7.50 (m, 3H), 7.44 (t, J=8.0 Hz, 1H), 5.02 (s, 2H), 4.03 (t, J=8.0 Hz,
2H), 3.63 (t, J=8.0 Hz, 2H), 1.84-1.62 (m, 4H), 1.48-1.24 (m, 4H),
1.02 (t, J=8.0 Hz, 3H), 0.91 (t, J=8.0 Hz, 3H) ppm. 13C NMR (100
MHz, CDCl3): δ = 195.7, 133.9, 132.0, 131.5, 128.7, 128.6, 128.3,
126.4, 125.9, 125.5, 124.2, 55.0, 52.5, 40.7, 29.3, 28.5, 20.2, 20.1,
13.9, 13.7 ppm. HRMS (ESI) m/z [M+H]+ Calcd for C20H28NS2
346.1658; found 346.1661.
Benzyl dibutylcarbamodithioate (3zc): The synthesis was carried
out according to the typical procedure, and the residue was purified
by flash chromatography on silica gel (petroleum ether/ethyl acetate
= 100:1) to give compound 3zc (69 %) as a yellow oil. 1H NMR (400
MHz, CDCl3): δ = 7.42 (d, J=8.0 Hz, 2H), 7.37-7.27 (m, 3H), 4.57 (s,
2H), 3.99 (t, J=8.0 Hz, 2H), 3.67 (t, J=8.0 Hz, 2H), 1.81-1.66 (m,
4H), 1.44-1.31 (m, 4H), 1.04-0.92 (m, 6H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 195.7, 136.2, 129.4, 128.6, 127.4, 55.1, 52.5, 42.4, 29.4,
28.4, 20.2, 20.1, 13.9, 13.7 ppm. HRMS (ESI) m/z [M+H]+ Calcd for
C16H26NS2 296.1501; found 296.1505.
Acknowledgements
We thank the foundation support from National Natural Science
Foundation of China (21302150), foundation of Chen-Guang
program from Hubei Association for Science and Technology,
foundation of Chutian distinguished fellow from Hubei Provincial
Department of Education, foundation of Highend Talent
Cultivation Program from Wuhan Institute of Technology. Z.-B. D.
acknowledges the Humboldt Foundation and China Scholarship
Council for a fellowship.
4-Bromobenzyl dibutylcarbamodithioate (3zd): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 100:1) to give compound 3zd (83 %) as a
yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.49-7.41 (m, 2H), 7.33-
7.25 (m, 2H), 4.53 (s, 2H), 3.98 (t, J=8.00 Hz, 2H), 3.66 (t, J=8.0 Hz,
2H), 1.81-1.63 (m, 4H), 1.45-1.30 (m, 4H), 1.04-0.92 (m, 6H) ppm.
13C NMR (100 MHz, CDCl3): δ = 195.1, 135.7, 131.6, 131.0, 121.3,
55.2, 52.6, 41.3, 29.4, 28.4, 20.2, 20.1, 13.8, 13.7 ppm. HRMS (ESI)
m/z [M+H]+ Calcd for C16H25BrNS2 374.0607; found 374.0611.
Keywords: metal-free • coupling • water • dithiocarbamate •
2-Bromobenzyl dibutylcarbamodithioate (3ze): The synthesis
was carried out according to the typical procedure, and the residue
was purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate = 100:1) to give compound 3ze (84 %) as a
yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.57 (t, J=8.0 Hz, 2H),
7.26 (t, J=8.00 Hz, 1H), 7.12 (t, J=8.0 Hz, 1H), 4.73 (s, 2H), 3.98 (t,
J=8.0 Hz, 2H), 3.66 (t, J=8.0 Hz, 2H), 1.79-1.64 (m, 4H), 1.45-1.29
(m, 4H), 1.04-0.89 (m, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ =
195.2, 136.3, 132.8, 131.6, 129.1, 127.6, 125.0, 55.2, 52.6, 42.3,
29.4, 28.4, 20.2, 20.1, 13.9, 13.8 ppm. HRMS (ESI) m/z [M+H]+
Calcd for C16H25BrNS2 374.0607; found 374.0609.
synthesis
[1]
[2]
[3]
[4]
V. Vindigni, R. Cortivo, L. Iacobellis, G. Abatangelo, B. Zavan, Int. J.
Mol. Sci., 2009, 10, 2972-2985.
A. Kamble, R. Kamble, S. Dodamani, S. Jalalpure, V. Rasal, M. Kumbar,
S. Joshi, S. Dixit, Arch. Pharm. Res., 2017, 40, 444-457.
T. Magoshi, H. Z. Cherif, S. Ohya, Y. Nakayama, T. Matsuda, Langmuir,
2002, 18, 4862-4872.
G. Brahemi, F. R. Kona, A. Fiasella, D. Buac, J. Soukupova, A.
Brancale,A. M. Burger, A. D. Westwell, J. Med. Chem., 2010, 53, 2757-
2765.
4-Nitrobenzyl dibutylcarbamodithioate (3zf): The synthesis was
carried out according to the typical procedure, and the residue was
purified by flash chromatography on silica gel (petroleum ether/ethyl
acetate = 100:1) to give compound 3zf (87 %) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 8.18 (d, J=8.0 Hz, 2H), 7.58 (d, J=8.0
Hz, 2H), 4.70 (s, 2H), 3.98 (t, J=8.0 Hz, 2H), 3.67 (d, J=8.0 Hz, 2H),
[5]
[6]
[7]
P. W. Miller, D. Bender, Chem. Eur. J., 2012, 18, 433-436.
I. Kaur, S. K. Verma, Surf. Coat. Tech., 2010, 205, 2082-2090.
H. S. Mani, Z. A. Touchente, A. Lamouri, B. Carbonnier, J. F. Caron, K.
Benzarti, M. M. Chehimi, RSC Adv., 2016, 6, 88126-88134.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801520
European Journal of Organic Chemistry
FULL PAPER
[8]
[9]
A. Z. Halimehjani, M. H. Shayegan, M. M. Hashemi, B. Notash, Org.
Synthesis, 2017, 49, 5211-5216; d) M. Liu, M. T. Zeng, W. Xu, L. Wu, Z.
B. Dong, Tetrahedron Lett., 2017, 58, 4352-4356; e) W. Xu, M. T. Zeng,
M. Liu, S. S. Liu, Y. S. Li, Z. B. Dong, Synthesis, 2017, 49, 3084-3090; f)
X. Liu, Q. Cao, W. Xu, M. T. Zeng, Z. B. Dong, Eur. J. Org. Chem.,
2017, 5795-5799; g) Q. Cao, H. Y. Peng, Y. Cheng, Z. B. Dong,
Synthesis, 2018, 50, 1527-1534; h) W. Xu, F. Gao, Z. B. Dong, Eur. J.
Org. Chem., 2018, 821-828; i) M. T. Zeng, M. Wang, H. Y. Peng, Y.
Cheng, Z. B. Dong, Synthesis, 2018, 50, 644-650; j) Z. B. Dong, M.
Wang, H. Zhu, X. Liu, C. Z. Chang, Synthesis, 2017, 49, 5258-5262; k)
M. T. Zeng, W. Xu, M. Liu, X. Liu, C. Z. Chang, H. Zhu, Z. B. Dong, Syn.
Comm., 2017, 47, 1434-1440.
Lett., 2012, 14, 3838-3841.
T. Guntreddi, R. Vanjari, K. N. Singh, Tetrahedron, 2014, 70, 3887-
3892.
[10] N. Azizi, F. Aryanasab, M. R. Saidi, Org. Lett., 2006, 8, 5275-5277.
[11] N. Azizi, E. Gholibeglo, RSC Advances, 2012, 2, 7413-7416.
[12] P. Rollin, Tetrahedron Lett., 1986, 27, 4169-4170.
[13] B. P. Bandgar, V. S. Sadavarte, L. S. Uppalla, J. Chem. Research (S),
2000, 450-451.
[14] V. K. Tiwari, A. Singh, H. A. Hussain, B. B. Mishra, V. Tripathi, Monatsh.
Chem., 2007, 138, 653-658.
[15] D. Enders, A. Rembiak, J. X. Liebich, Synthesis, 2011, 2, 281-286.
[16] A. Krasovskiy, A. Gavryushin, P. Knochel, Synlett, 2006, 5, 792-794.
[17] M. Carril, R. SanMartin, E. Dominguez, Chem. Soc. Rev., 2008, 37,
639-647.
[21] a) Q. Cao, Q. Yin, Q. Chen, Z. B. Dong, B. H. Han, Chem. Eur. J., 2017,
41, 9831-9837; b) W. Xu, M. T. Zeng, S. S. Liu, Y. S. Li, Z. B. Dong,
Tetrahedron Lett., 2017, 58, 4289-4292; c) Y. Cheng, X. Liu, Z. B. Dong,
Eur. J. Org. Chem., 2018, 815-820; d) H. Zhu, X. Liu, Y. Cheng, H. Y.
Peng, Y. S. Li, Z. B. Dong, Synthesis, 2018, 50, 2247-2254; e) X. Liu,
W. Xu, M. T. Zeng, M. Liu, C. Z. Chang, H. Zhu, Z. B. Dong, J. Chem.
Res., 2017, 41, 484-486.
[18] N. Azizi, F. Aryanasab, L. Tourkian, M. R. Saidi, Synthetic Commun.,
2011, 41, 94-99.
[19] N. Azizi, E. Gholibeglo, S. D. Nayeri, Monatsh Chem., 2012, 143, 1171-
1174.
[22] a) X. Liu, M. Liu, W. Xu, M. T. Zeng, H. Zhu, C. Z. Chang, Z. B. Dong,
Green Chem., 2017, 19, 5591-5598; b) X. Liu, H. Zhu, S. B. Zhang, Y.
Cheng, H. Y. Peng, Z. B. Dong, Tetrahedron Lett., 2018, 59, 3165-3170.
[20] a) Z. B. Dong, X. Liu, C. Bolm, Org. Lett., 2017, 19, 5916-5919; b) M. T.
Zeng, W. Xu, X. Liu, C. Z. Chang, H. Zhu, Z. B. Dong, Eur. J. Org.
Chem., 2017, 6060-6066; c) H. Zhu, X. Liu, C. Z. Chang, Z. B. Dong,
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Key Topic*: C(sp3)−S coupling
H.-Y. Peng and Z.-B. Dong*
Page No. – Page No.
Transition-metal-free
C(sp3)−S
coupling in water: synthesis of benzyl
dithiocarbamates
disulfides as organosulfur source
using
thiuram
Text for Table of Contents
*one or two words that highlight the emphasis of the paper or the field of the study
By the treatment of benzyl halides with tetraalkylthiuram disulfides (TMTD, TETD and TBTD), the desired C(sp3)-S coupling
products (benzyl dithiocarbamates) could be obtained in good to excellent yields. The protocol features advantages of
experimental simplicity, water as solvent, metal-free, good functional compatibility, good to excellent yields, illustrating its
potential synthetic value in the convenient preparation of some potentially biologically active compounds.
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