Reduced graphene oxide as recyclable catalyst for synthesis of Bis(aminothiocarbonyl)disulfides from secondary amines and carbon disulfide

Article abstract of DOI:10.1007/s10562-014-1257-x

The reaction of secondary amines with CS₂ under mild conditions using reduced graphene oxide (rGO) as a green catalyst was reported, which provided an efficient access to the one-pot synthesis of bis(aminothiocarbonyl) disulfides. The rGO can be recycled at least four times without any loss of catalytic activity. A plausible mechanism was proposed.

Full text of DOI:10.1007/s10562-014-1257-x

Catal Lett
DOI 10.1007/s10562-014-1257-x
Reduced Graphene Oxide as Recyclable Catalyst for Synthesis
of Bis(aminothiocarbonyl)disulfides from Secondary Amines
and Carbon Disulfide
•
Meishuang Wang Xianghai Song
•
Ning Ma
Received: 23 March 2014 / Accepted: 6 April 2014
Ó Springer Science+Business Media New York 2014
Abstract The reaction of secondary amines with CS2
under mild conditions using reduced graphene oxide (rGO)
as a green catalyst was reported, which provided an effi-
cient access to the one-pot synthesis of bis(aminothiocar-
bonyl)disulfides. The rGO can be recycled at least four
times without any loss of catalytic activity. A plausible
mechanism was proposed.
products of the dithiocarbamic acids, bis(aminothiocar-
bonyl)disulfides are generally produced by the reaction of
dithiocarbamic salts (often generated in situ from amines
and CS2) with large excess of oxidants, such as NaNO2 [4],
I2 [5], NaClO [6]. Recently, equimolecular CBr4 has been
reported to promote this transformation [7]; Mn(OAc)2 has
been involved as a catalyst under 1.7 bar of O2 at 50 °C
[8]. However, most of these oxidants are not clean, pro-
ducing unrecyclable wastes after the redox process.
Moreover, the yields of the some products are also unsat-
isfactory. Although H2O2 can oxidize dithiocarbamates to
synthesize thiram analogues, corrosive strong bases such as
NaOH and irritative acetic acid were often involved [9].
Therefore, more efficient and environmentally benign
method for synthesis of bis(aminothiocarbonyl)disulfides is
still of great importance.
Keywords Bis(aminothiocarbonyl)disulfides Á Reduced
graphene oxide Á Carbocatalyst Á Aerobic oxidation
1 Introduction
Bis(aminothiocarbonyl)disulfides play important role in
pharmaceutical therapy, crop protection and rubber man-
ufacture [1–3]. For example, disulfiram and thiram have
been involved in the treatment of chronic alcohol depen-
dence (Scheme 1). Thiram has also been used as an agro-
chemical to prevent fungal diseases in seeds and crops.
Furthermore, a variety of thiram analogues have been
synthesized and their monoglyceride lipase and aldehyde
dehydrogenase (ALDH) inhibitory activities have been
investigated [4, 5]. As the dehydrogenative coupling
Graphene (GP) and GP-related materials have been
focused on by numerous scientists from material, physics
and chemistry communities in the past decade [10–13].
Although various preparative methods for GP have been
established, many chemists tend to choose chemical
reduction of graphene oxide (GO, or graphite oxide), the
strongly oxidized product of graphite [14, 15]. GP prepared
through this route is also called reduced graphene oxide
(rGO) to distinguish from the others. GO and GP have been
widely investigated as catalyst supports in recent years
[16–19]. Besides, GO have been introduced into various
organic transformations as catalyst and oxidant by others
and us [20–35]. However, organic reactions catalyzed only
by rGO (or unmodified GP) have been rarely reported. The
catalytic activity of rGO has been demonstrated in reduc-
tion of nitrobenzene by hydrazine hydrate [36] and oxi-
dative degradation of phenols and methylene blue in water
by peroxymonosulfate [37]. GP nanofibers also served as
catalyst on hydrogen release of sodium alanate [38].
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1257-x) contains supplementary
material, which is available to authorized users.
M. Wang Á X. Song Á N. Ma
Department of Chemistry, School of Science, Tianjin University,
Tianjin 300072, China
N. Ma (&)
Collaborative Innovation Center of Chemical Science and
Engineering (Tianjin), Tianjin 300072, China
e-mail: mntju@tju.edu.cn
123

M. Wang et.al
Then KMnO4 (9.0 g) was added slowly in portions with the
reaction temperature below 20 °C. The ice bath was
removed and the reaction mixture was warmed by water
bath to keep the temperature at 35 °C for 30 min, at which
time deionized water (138 mL) was added slowly. External
heating was introduced to maintain the reaction tempera-
ture at 98 °C for 15 min, then the heat was removed and
the reaction was cooled to room temperature and poured
into ice water (420 mL). Then 30 % H2O2 (3 mL) was
added, the suspension was filtered and the solid was stirred
with 30 % HCl (200 mL). The mixture was filtered,
washed by deionized water and filtered repeatedly until the
pH of the filtrate was neutral. Finally, GO was dried in a
desiccator with P2O5 under vacuum until its weight was
constant.
S
S
S
S
N
N
N
S
N
S
S
S
Scheme 1 Disulfiram (left) and thiram (right)
As the continuation of our investigations on the reac-
tions of dithiocarbamates [39–41], the coupling of dith-
iocarbamic acids with themselves or other radical acceptors
has attracted our attention. Considering air (or oxygen) is a
clean oxidant [42–44], we attempted to conduct coupling
reaction of dithiocarbamates under air atmosphere. By
using some transition metal catalysts, such as Fe, Cu and
Mn salts, the reaction was accelerated. Unsatisfactorily,
byproducts often appeared which made careful column
separation inevitable. From the literatures, we learn that
GP-like materials might help to activate oxygen and per-
oxymonosulfate and produce active radicals [32, 37].
Hence, rGO was added into the reaction instead of transi-
tion metal salts. We were glad to find that rGO could
catalyze the reaction and lead to excellent selectivity.
Therefore, we describe herein a new synthetic method to
thiram analogues, in which rGO serves as a recyclable
carbocatalyst and air acts as the oxidant.
2.2.2 Preparation of rGO
The rGO was prepared according to the method described in
the literature [46]. GO power (100 mg) was added into a flask
containing deionized water (100 mL), yielding an inhomo-
geneous yellow–brown dispersion. This dispersion was son-
icatedusingaKQ3200DEultrasonicbathcleaner (100 W)for
1 h. Then hydrazine hydrate (1.0 mL) was added and the
solution was refluxed with stirring for 24 h. The reaction was
cooled to room temperature, and the product was isolated by
filtration, washed copiously with deionized water
(5 9 100 mL) and methanol (5 9 100 mL), and dried in a
desiccator with P2O5 under vacuum until its weight was
constant.
2 Experimental
2.1 Materials and Methods
All reagents were purchased from commercial sources and
used without any further purification. The melting points
were obtained on a Laboratory Devices X-4 melting
apparatus and were uncorrected. FT-IR spectra (KBr) were
recorded on a Bruker ALPHA spectrophotometer in the
2.3 Typical Procedure for the Synthesis of Thiuram
Disulfides 2a–2l
Amine (1 or 2 mmol of 1a, 1c–1d, 1f–1j; 15 mmol of 1b;
2 mmol of 1e, 1i and 2.4 mmol of Et3N), CS2 (2 equiv. of
1) and rGO (10 wt% of 1) was added to 5 mL (20 mL for
1b) of ethanol. The reaction mixture was stirred under
ambient temperature under open-air for 14 h. After com-
pletion of the reaction, the catalyst was filtered and washed
with CH2Cl2 (3 9 5 mL). The first filtrate (ethanol solu-
tion) was condensed under vacuum and the residue was
combined with the other filtrates (CH2Cl2 solutions). The
combined solutions were washed with 0.2 M HCl
(3 9 5 mL) and dried over MgSO4. The solvent was
removed under vacuum and the residue solid was dissolved
in least volume of CH2Cl2. After ca. 5 mL of MeOH
(10 mL of EtOH for 2b) was added, the appeared precip-
itate was filtered and dried to give the desired product
(silica gel column chromatography for 2c).
1
range of 400–4,000 cm-1. H and 13C NMR spectra were
recorded in CDCl3 using TMS as an internal standard on a
Bruker AVANCE III 400 spectrometer at 400 and
100 MHz, respectively. X-ray diffraction (XRD) mea-
surements were performed using a BDX-3300 X-ray dif-
fractometer operated with Cu Ka radiation. TEM images
were carried out on a JEOL 2100F microscope.
2.2 Preparation of Catalyst
2.2.1 Preparation of GO
GO was prepared by oxidation of natural graphite powder
(325 mesh, Alfa Aesar) according to the Hummers method
[45]. Graphite powder (3.0 g) and NaNO3 (1.5 g) was
slowly added into concentrated H2SO4 (69 mL) with stir-
ring in a 500 mL flask, and the mixture was cooled to 0 °C.
Synthesis of 2k Amine 1k (2 mmol), DABCO (4 mmol)
and CS2 (4 mmol) was added to ethanol (5 mL) in an ice
123

Reduced Graphene Oxide as Recyclable Catalyst
bath, then the mixture was stirred for 1 h. The ice bath was
removed and the reaction mixture was stirred at room
temperature for 5 h. After that, rGO (10 wt % of 1k) was
added and the reaction mixture was stirred under open-air
for 14 h. The isolation of 2k was same as the above typical
procedure.
3 Results and Discussion
3.1 Characterization of rGO
Figure 1 shows the typical FT-IR spectra of GO and pris-
tine rGO. For GO, the characteristic peaks appear for
carbonyl C=O (1,725 cm-1), epoxy C–O (1,234 cm-1) and
hydroxy C–O (1,053 cm-1). After chemical reduction, the
peak at 1,725 cm-1 for carbonyl C=O vanished, and the
peaks for other oxygen-functional groups were reduced
dramatically. The peaks at 1,567 cm-1 is attributed to the
aromatic C=C group.
Fig. 2 XRD patterns of GO (A), pristine rGO (B), rGO after being
used five times (C) and graphite (D)
Figure 2 shows the X-ray diffraction (XRD) patterns of
graphite, GO and pristine rGO. Graphite showed a sharp
and intensive peak at 2h = 26.38, corresponding to an
interlayer d-spacing of 0.339 nm. After oxidation, this 002
diffraction peak of graphite disappeared. The GO exhibited
a sharp diffraction peak at 2h = 11.88, corresponding to an
interlayer d-spacing of 0.749 nm. The increase in the
interlayer spacing is attributed to the oxygen-functional
groups located on the graphene sheets. After being reduced
by hydrazine hydrate, no apparent peaks were detected in
the pattern of rGO, indicating that the oxygen-functional
groups were removed during the reduction process.
Figure 3 shows the TG curve of pristine rGO. Slight loss
of mass below 600 °C indicates the efficient removal of
Fig. 3 TG analysis of pristine rGO (A), rGO after being used five
times (B)
thermally labile oxygen-functional groups by the reduction
of GO.
Figure 4 shows the TEM image of the pristine rGO. It
revealed that rGO material consisted of outspread or
aggregated sheets with numerous wrinkles.
3.2 Reaction Conditions and Scope
We chose the reaction of dibenzylamine (1a) with CS2 as
the model reaction. The reaction took place readily when
mixing 1a, CS2 and rGO (10 wt% of 1a) under open-air at
room temperature (entry 1, Table 1). The yield of 2a was
poor in nitrogen atmosphere, which indicated that oxygen
in air was the final oxidant (entry 2, Table 1). The appro-
priate solvents were screened to be methanol, ethanol,
dichloromethane, acetonitrile (entries 1, 3–8, Table 1).
Fig. 1 FT-IR of GO (A), pristine rGO (B), rGO after being used five
times (C)
123

M. Wang et.al
obtained in good yields (entries 2-4, Table 2). The HCl salt
of dimethylamine reacted with CS2 to afford thiram 2e in
the presence of rGO and base (entries 5, Table 2). Cyclic
secondary amines were also converted to corresponding
bis(aminothiocarbonyl)disulfides in satisfactory yields
(entries 6–8, Table 2). Morpholine was treated with CS2 to
give 2i in moderate yields both in EtOH and in DCM due to
the poor solubility of the corresponding dithiocarbamate.
Although using water as solvent did not increase the yield,
the reaction in a mixed solvent of EtOH-H2O underwent
smoothly (entry 9, Table 2). Cyclohexylmethylamine was
transformed to 2j in good yield (entry 10, Table 2). In
contrast, aromatic secondary amine was less active and
addition of strong base such as DABCO facilitated the
reaction (entry 11, Table 2). Interestingly, N,O-dim-
ethylhydroxylamine hydrochloride was converted to the
corresponding product 2l in the presence of Et3N in a good
yield (entry 12, Table 2). Notably, all solid products pre-
cipitated in a mixed solvent of DCM–MeOH (or DCM–
EtOH) and were isolated by filtration, and no further
purification was needed.
Fig. 4 TEM image of pristine rGO
3.3 Reuse of rGO
Table 1 Reactions of dibenzylamine and CS2 in different solvents
Ph
S
The recycling of rGO was examined in the preparation of
disulfiram 2b. The catalyst was filtered off after the com-
pletion of the reaction. It was washed thoroughly with
dichloromethane and reused in the reaction system. As
shown in Table 3, rGO remained high catalytic activity at
the fifth run. IR (Fig. 1), XRD (Fig. 2) and TG (Fig. 3)
data of the recovered rGO were well consistent with those
of pristine rGO.
10 wt% catalyst
rt, 14 h, open-air
S
N
Ph
+
Ph
CS2
Ph
N
S
Ph
N
H
S
Ph
2a
1a
Entry
Solvent
Catalyst
Yield (%)a
1
EtOH
rGO
rGO
rGO
rGO
rGO
rGO
rGO
rGO
Graphite
GO
92
12b
2
EtOH
3
MeOH
THF
90
4
79
3.4 Catalytic Mechanism
5
CH2Cl2
CH3CN
Toluene
Acetone
EtOH
92
6
91
The existence of unpaired electrons at the edges of
graphene has been well documented [32, 37, 47]. More
recently, Loh et al. discovered that nanovoids formed
during base-acid treatment of GO and unpaired electrons
generated in these structure defects. These electrons,
together with the unpaired electrons at the edges of GO,
could activate O2 to form ÁO2- and led to aerobic oxidative
coupling of benzylamines. Enlightened by their pioneering
mechanism study, we suggest that an unpaired electron at
the edge of rGO can reduce O2 to form ÁO2- similarly and
initiate the coupling reaction of dithiocarbamic acids. The
7
81
8
72
9
Trace
10
11
a
EtOH
20
22c
EtOH
None
Isolated yield
b
c
Under N2 atmosphere
Reaction time was 72 h
Ethanol was preferred because of its safety and cheapness.
Interestingly, graphite did not show catalytic activity in the
reaction (entry 9, Table 1), and GO also showed low aci-
tivity (entry 10, Table 1). Without rGO, 2a was obtained
only in 22 % yield when the reaction time was extended to
72 h (entry 11, Table 1).
-
ÁO2 abstracts hydrogen atom of compound I to form
HOO- and radical II. In the meantime, HOO- reacts with
I to form H2O2 and dithiocarbamate ion III. The rGO
cation accepts an electron from III, generating another
radical II and the rGO with unpaired electron. Then the
coupling of II took place to get the coupling product
(Scheme 2). Although graphite and rGO have the same sp2
Then the scope of the reaction was investigated. In the
cases of dialkylamines, the corresponding products were
123

Reduced Graphene Oxide as Recyclable Catalyst
Table 2 Scope of the substrates
Enty
1
Substrate
Product
Yield (%)a
92
Ph
S
N
Ph
S
Ph
N
Ph
1a
2a
Ph
N
N
S
H
S
Ph
S
S
N
S
S
NH
2
3
1b
1c
2b
2c
84
83
S
S
S
S
N
NH
N
S
H
N
S
4
1d
2d
73
N
N
S
S
S
S
N
N
S
S
NH·HCl
NH
5
6
1e
1f
2e
2f
84
88
N
N
S
S
S
S
S
S
S
S
NH
N
N
N
N
7
8
1g
1h
1i
S
S
S
S
2g
2h
2i
91
67
N
N
N
N
S
S
S
S
S
S
S
S
NH
49, 41b,
44c, 78d
O
NH
O
9
O
H
N
10
1j
2j
75
H
N
S
S
N
N
11
12
1k
1l
S
S
2k
2l
40
78
N
N
S
S
S
S
O
NH
H
l
C
O
O
a
Unless otherwise indicated, the reaction conditions were: molar ratio of 1/CS2 = 1:2, rGO (10 wt% of 1), EtOH as solvent, rt, under open-air,
14 h
b
CH2Cl2 as solvent
c
H2O as solvent
d
EtOH–H2O (5:1) as solvent
123

M. Wang et.al
Table 3 Reuse of the catalyst
S
N
S
10 wt% rGO
N
S
+
N
H
CS2
EtOH, rt,14h
open-air
S
Run
1
2
3
4
5
Isolated yield (%)
84
87
83
84
88
Scheme 2 Plausible
mechanism for the formation of
thiuram disulfides
S
R1
N
R2
S
e−
II
R1
N
S
O2
R1
R2
S−
N
R2
III
S
H
2O2
S
S
e−
S
N R2
R1
I
−
H
OO
IV
R2
R1
−
O2
N
H
S
S
R1
R1
N
S
+
N
R2
H
S
R2
II
CS2
I
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