An expedient, fast and competent synthesis of organic dithiocarbamates over nanocrystalline MgO in water at room temperature

Article abstract of DOI:10.1016/j.tetlet.2011.09.131

A new, expeditious, efficient and eco-friendly method for the synthesis of organic dithiocarbamates has been achieved at room temperature using basic nanocrystalline MgO catalyst in aqueous condition. The method has been applied for the synthesis of a range of compounds with variable functionalities in excellent yield and selectivity.

Full text of DOI:10.1016/j.tetlet.2011.09.131

Tetrahedron Letters 52 (2011) 6584–6586
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Tetrahedron Letters
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An expedient, fast and competent synthesis of organic dithiocarbamates
over nanocrystalline MgO in water at room temperature
Bikash Karmakar a, Julie Banerji b,
⇑
a Gobardanga Hindu College, Department of Chemistry, Khantura, North 24 Parganas 743 273, India
b Centre of Advanced Studies on Natural Products including Organic Synthesis, Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata 700 009, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A new, expeditious, efficient and eco-friendly method for the synthesis of organic dithiocarbamates has
been achieved at room temperature using basic nanocrystalline MgO catalyst in aqueous condition. The
method has been applied for the synthesis of a range of compounds with variable functionalities in excel-
lent yield and selectivity.
Received 26 August 2011
Revised 26 September 2011
Accepted 28 September 2011
Available online 5 October 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent synthesis
Dithiocarbamates
Nanocrystalline MgO
Heterogeneous
Water chemistry
In recent times increased attention is being focused on the
development of eco-friendly solid acid/base catalysts for organic
synthesis. Removing organic solvents has become an important
factor towards developing benign chemical technologies due to
their high toxicity. As a result, organic reactions in aqueous media
have gained high priority in view of green methodology.1 The use
of water is also preferred due to its abundance, being economical
and high polarity. It shows higher reactivity and selectivity com-
pared to other conventional organic solvents due to its strong
hydrogen bonding ability.2 The use of water in multicomponent
organic reactions has gained much importance.3
Organic dithiocarbamates have received much attention due to
their interesting chemistry and wide utility. These compounds
have shown wide applications as pesticides, fungicides in agricul-
ture,4 in the vulcanization of rubber,5 and in radical chain transfer
agents in the reversible addition fragmentation chain transfer
(RAFT) polymerizations.6 They have been extensively used as inter-
mediates in organic synthesis,7 for the protection of amino groups
in peptide chemistry,8 as linker in solid phase organic synthesis,9
and recently in the synthesis of ionic liquids.10 Dithiocarbamates
are widely used in the synthesis of trifluoromethylamines, thio-
ureas, aminobenzimidazoles, isothiocyanates, alkoxyamines and
2-imino-1,3-dithiolanes.11 They also have antihistaminic, antibac-
terial and anticancer activities.12
and toxic. Dithiocarbamates can be easily synthesized by coupling
an amine, CS2 and an electrophilic reagent. Several methods have
been developed for the preparations of dithiocarbamates in view
of their importance. Some of the methods involve the use of vari-
ous homogeneous bases and solvents like DMSO, DMF, MeOH to
promote the reaction which are not considered as eco-friendly.14
Several researchers15–17 have developed some green protocol for
the synthesis of these compounds. However, these methods suffer
from the disadvantage that they take a long time for completion.
We have developed the synthesis of dithiocarbamates following
an eco-friendly pathway in very short time, involving Michael
addition as an intermediate step catalysed over nanocrystalline
MgO.
In continuation of our efforts for the developing synthetic meth-
odologies for the production of various biologically important moi-
eties using heterogeneous nanocatalysts,18 we wish to report for
the first time use of nanocrystalline MgO catalysed one-pot three
component synthesis of dithiocarbamates in water under ambient
conditions in high yield (Scheme 1). Recently, we have published
our work for the synthesis of Betti bases over nanocrystalline
MgO at aqueous condition.19 Structural characterization, active
sites and method of synthesis of NP MgO have been discussed in
detail in the earlier work.
A very simple protocol was followed in the reaction process.20
A
The classical synthesis of dithiocarbamates involves the use of
mixture of an amine (1.0 mmol), CS2 (3.0 mmol) and a Michael
acceptor (1.3 mmol) was stirred in water at room temperature over
nano MgO catalyst. The progress was checked by TLC and after
work-up excellent yields of the product was obtained. No other
additive was necessary to promote the reaction.
thiophosgene and its substituted derivatives,13 which are costly
⇑
Corresponding author. Tel.: +91 33 2350 8386; fax: 91 33 2351 9755.
E-mail address: juliebanerji47@gmail.com (J. Banerji).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.131

B. Karmakar, J. Banerji / Tetrahedron Letters 52 (2011) 6584–6586
6585
S
R
R
NP MgO
N
X
+
CS2
S
NH
+
X
rt, Water
R'
R'
Scheme 1. Synthesis of dithiocarbamates over nanocrystalline MgO in water.
Table 1
Screening of catalysts in the synthesis of dithiocarbamates over nano MgOa
Table 3
Synthesis of dithiocarbamates over nanocrystalline MgOa
Entry
Catalyst
Time (h)
Yield (%)
Entry Amines
Michael acceptor
Time (h) Yield (%)
1
2
3
4
5
6
7
CuO nanopowder
Basic Al2O3
Silica gel
SBA 15
TUD-1
6
52
1
2
3
4
5
6
Pyrrolidine
Methyl acrylate
Acrylonitrile
Acrylamide
1.0
1.2
1.5
0.5
1.0
2.0
92
94
88
95
92
73
20
20
12
12
1.0
1.0
9517
8417
73
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
x-Nitro styrene
68
78
92
Benzylidene acetophenone
4-Nitrobenzylidene
acetophenone
Bulk MgO
Nano MgO
7
8
9
10
11
12
13
14
15
16
Piperidine
Piperidine
Piperidine
Piperdine
Acrylonitrile
Acrylamide
Methyl acrylate
Benzylidene acetophenone
x-Nitro styrene
Acrylonitrile
Acrylamide
1.2
2.0
1.5
1.2
0.7
1.0
2.0
1.5
1.5
1.0
88
85
90
91
93
88
82
85
84
86
a
Reagents and conditions: pyrrolidine/methyl acrylate/CS2 = 1.0:1.2:3.0, catalyst
10 mg, room temperature, water, isolated yield, bold entry signifies the best
condition.
Piperdine
Morpholine
Morpholine
Morpholine
Cyclohexylamine Acrylonitrile
Benzylamine Acrylonitrile
Table 2
Screening of solvents in the synthesis of dithiocarbamates over nano MgOa
Methyl acrylate
Entry
Solvent
Time (h)
Yield (%)
1
2
3
4
n-Hexane
THF
MeOH
Water
6
6
3
1
n.r
n.r
76
92
a
Reagents and conditions: amine/Michael acceptor/CS2 = 1.0:1.2:3.0, catalyst
10 mg, room temperature, water, isolated yield.
a
Reagents and conditions: pyrrolidine/methyl acrylate/CS2 = 1.0:1.2:3.0, catalyst
Table 4
Reusability study of MgO
10 mg, room temperature, isolated yield, bold entry signifies the best condition.
Entry
Yielda (%)
During the course of the reaction, standardization of reaction
conditions appeared important. The reaction between pyrrolidine,
carbon disulphide and methyl acrylate as the Michael acceptor was
chosen as a probe. Optimization started with the study of catalyst
variation. A wide range of catalysts viz., CuO nanopowder, basic
Al2O3, silica gel, mesoporous silica, bulk MgO and nanocrystalline
MgO was used in the reaction in aqueous condition at room tem-
perature. Notably, nano MgO afforded the best results amongst
the different kinds of solid media used. These have been shown
in Table 1. It seems interesting to mention that CuO provided the
corresponding aza-Michael product in major amount compared
to the desired dithiocarbamate. Basic alumina, although efficient,
took longer reaction time. With silica gel and mesoporous silica
(SBA-15 and TUD-1) only moderate yields were obtained. How-
ever, with bulk MgO some undetected byproduct was produced
along with the desired compound. So, nanocrystalline MgO proved
to be the best catalyst in water.
Nano MgO worked best in aqueous condition as shown in Table
2. Among the different tested conventional organic solvents like
n-hexane, THF and methanol, none of the solvents proved satisfac-
tory in terms of reaction time and yield. With hexane and THF the
reaction did not proceed at all.
After standardization of the reaction conditions, the scope and
generality of these conditions with other substrates were exam-
ined by using a variety of primary and secondary amines and dif-
1
2
3
4
94
92
88
87
a
Isolated yield after each run.
acrylamide,
x-nitro styrene, benzyledene acetophenone and 4-ni-
tro benzyledene acetophenone (Table 3, entries 1–6). In all the
cases excellent yields were obtained in short time except with
4-nitrobenzyledene acetophenone which afforded comparatively
lower yield due to its lower electrophilicity (entry 6). Similarly,
other aliphatic amines like piperidine, morpholine, cyclohexyl
amine and benzyl amine also reacted with different electrophiles
efficiently generating high yields (Table 3, entries 7–16).
Recyclability of nanocrystalline MgO was examined through the
reaction of pyrrolidine, CS2 and acrylonitrile in water. After com-
pletion of the reaction, the product was extracted with diethyl
ether from the reaction mixture. The aqueous part containing the
MgO catalyst was recovered and reused as such for subsequent
reactions with fresh batch of reactants. It was found that MgO
could be recycled three times without significant loss of yield.
The reusability test has been shown in Table 4.
Nanocrystalline MgO contains large number of basic sites such
as O2À and OÀ and Mg2+ as Lewis acid sites. The initial mechanism
goes through the formation of dithiocarbamic acid where Mg2+ is
involved in activating carbon disulphide. This acid anion then
undergoes Michael addition promoted by Lewis and Bronsted basic
sites with the different acceptors to give the dithiocarbamate as
the final product.
In conclusion, an environmentally benign, highly efficient and
simple protocol for the synthesis of various structurally divergent
dithiocarbamate derivatives has been developed by one-pot
ferent electrophiles (Michael acceptors or
a,b-unsaturated
compounds). The results have been summarized in Table 3. All
the reactions were performed smoothly under optimized condi-
tions by stirring all reagents together in water in the presence of
nanocrystalline MgO and all the reactions were satisfactorily
completed within 1.0–2.0 h at ambient conditions. Using
pyrrolidine as cyclic secondary amine reactions were carried out
with different Michael acceptors like methyl acrylate, acrylonitrile,

6586
B. Karmakar, J. Banerji / Tetrahedron Letters 52 (2011) 6584–6586
Maleki, H.; Saidi, M. R. Tetrahedron Lett. 2009, 50, 2747. and references cited
therein.
reaction of wide range of amines, carbon disulphide and an array of
Michael acceptors with excellent yield in the presence of nanocrys-
talline MgO as catalyst. The reaction is (i) clean, (ii) highly expedi-
tious, (iii) involves water as the green solvent and (iv) occurs at
ambient conditions.
12. (a) Safak, C.; Erdogan, H.; Yesilada, A.; Erol, K.; Cimgi, I. Arzneim. Forsch. 1992,
42, 123; (b) Aboul-Fadl, T.; El-Shorbagi, A. Eur. J. Med. Chem. 1996, 31, 165; (c)
Nagano, R.; Shibata, K.; Naito, T.; Fuse, A.; Asano, K.; Hashizume, T.; Nakagawa,
S. Antimicrob. Agents Chemother. 1997, 41, 2278; (d) Gerhauser, C.; You, M.; Liu,
J.; Moriarty, R. T.; Hawthorne, M.; Mehta, R. G.; Moon, R. C.; Pezzuto, J. M.
Cancer Res. 1997, 57, 272; (e) Ge, Z. M.; Li, R. T.; Cheng, T. M.; Lai, C. S.; Li, R. T.
Bioorg. Med. Chem. Lett. 2006, 16, 4214; (f) Wang, Y. Q.; Ge, Z. M.; Hou, X. L.;
Cheng, T. M.; Li, R. T. Synthesis 2004, 675.
Acknowledgements
13. (a) Burke, J. T. R.; Bajwa, B. S.; Jacobsen, A. E.; Rice, K. C.; Streaty, R. A.; Klee, W.
A. J. Med. Chem. 1984, 27, 1570; (b) Walter, W.; Bode, K. D. Angew. Chem., Int. Ed.
1967, 6, 281.
14. (a) Salvatore, R. N.; Sahab, S.; Jung, K. W. Tetrahedron Lett. 2001, 42, 2055; (b)
Chaturvedi, D.; Ray, S. Tetrahedron Lett. 2006, 47, 1307; (c) Wang, Y.-Q.; Ge, Z.-
M.; Hou, X.-L.; Cheng, T.-M.; Li, R.-T. Synthesis 2004, 5, 675.
Thanks are accorded to Sri S. Chatterjee and Sri S. Bhowmick,
Organic Instrumentation Laboratory, Department of Chemistry,
University of Calcutta, for technical assistance. B.K. acknowledges
UGC for the financial assistance under minor research project.
15. (a) Ranu, B. C.; Saha, A.; Banerjee, S. Eur. J. Org. Chem. 2008, 519; (b) Bhadra, S.;
Saha, A.; Ranu, B. C. Green Chem. 2008, 10, 1224.
Reference and notes
16. (a) Ziyaei-Halimajani, A.; Saidi, M. R. Can. J. Chem. 2006, 84, 1515; (b) Saidi, M.
R.; Azizi, N.; Aryanasab, F.; Torkiyan, L.; Ziyaei, A. J. Org. Chem. 2006, 71, 3634;
(c) Saidi, M. R.; Azizi, N.; Aryanasab, F. Org. Lett. 2006, 8, 5275; (d) Saidi, M. R.;
Azizi, N.; Ebrahimi, F.; Aakbari, E.; Aryanasab, F. Synlett 2007, 2797.
17. Xia, S.; Wang, X.; Ge, Z.; Cheng, T.; Li, R. Tetrahedron 2009, 65, 1005.
18. (a) Karmakar, B.; Nayak, A.; Chowdhury, B.; Banerji, J. ARKIVOC 2009, XII, 209;
(b) Postole, G.; Chowdhury, B.; Karmakar, B.; Pinki, K.; Banerji, J.; Auroux, A. J.
Catal. 2010, 269, 110; (c) Karmakar, B.; Chowdhury, B.; Banerji, J. Catal.
Commun. 2010, 11, 601; (d) Karmakar, B.; Banerji, J. Tetrahedron Lett. 2010, 51,
3855; (e) Karmakar, B.; Sinhamahapatra, A.; Panda, A. B.; Banerji, J.;
Chowdhury, B. Appl. Catal. A: Gen. 2010, 392, 111.
1. (a) Li, C.-J. Chem. Rev. 2005, 105, 3095; (b) Li, C.-J.; Chan, T.-H. Organic Reactions
in Aqueous Media; Wiley: NewYork, 1997.
2. Ranu, B. C.; Banerjee, S. Tetrahedron Lett. 2007, 48, 141.
3. (a) Pirrung, M. C.; Das Sharma, K. J. Am. Chem. Soc. 2004, 126, 444; (b)
Kandhasamy, K.; Gnanasambandam, V. Curr. Org. Chem. 2009, 13, 1820.
4. (a) Marinovich, M.; Viviani, B.; Capra, V.; Corsini, E.; Anselmi, L.; D’Agostino, G.;
Nucci, A. D.; Binaglia, M.; Tonini, M.; Galli, C. L. Chem. Res. Toxicol. 2002, 15, 26;
(b) Len, C.; Boulogne-Merlot, A. S.; Postel, D.; Ronco, G.; Villa, P.; Goubert, C.;
Jeufrault, E.; Mathon, B.; Simon, H. J. Agric. Food Chem. 1996, 44, 2856.
5. Bergendorff, O.; Hansson, C. J. Agric. Food Chem. 2002, 50, 1092.
6. Lai, J. T.; Shea, R. J. Polym. Sci., Part A Polym. Chem. 2006, 44, 4298; (b) Dureaault,
A.; Gnanou, Y.; Taton, D.; Destarac, M.; Leising, F. Angew. Chem., Int. Ed. 2003,
42, 2869; (c) Bathfield, M.; D’Agosto, F.; Spitz, R.; Charreyre, M. T.; Delair, T. J.
Am. Chem. Soc. 2006, 128, 2546.
7. (a) Tsuboi, S.; Takeda, S.; Yamasaki, Y.; Sakai, T.; Utka, M.; Ishida, S.; Yamada, E.;
Hirano, J. Chem. Lett. 1992, 1417; (b) Katrizsky, A. R.; Singh, S.; Mahapatra, P. P.;
Clemense, N.; Kirichenko, K. ARKIVOC 2005, 9, 63.
8. Greene, T. W.; Wuts, P. G. M. Protecting Groups in Organic synthesis, 3rd ed.;
Wiley Interscience: NewYork, 1999. p 484.
19. Karmakar, B.; Banerji, J. Tetrahedron Lett. 2011, 52, 4957.
20. A mixture of an amine (1.0 equiv), a Michael acceptor (1.2 equiv), and CS2
(3.0 equiv) was stirred at room temperature in aqueous (just moist) condition
in the presence of 10 mg of nano MgO catalyst. After completion of the reaction
(indicated by TLC), the reaction mixture was extracted with diethyl ether. The
extract was concentrated under reduced pressure and purified by column
chromatography using 100–200 mesh silica gel with ethyl acetate/hexane (6–
10%) as eluent. The isolated compounds were characterized from mp, IR, 1H
NMR, 13C NMR spectrometry and spectral analysis (C, H, and N). Spectroscopic
data for one of the characteristic compound has been provided below.
Pyrrolidine-1-carbodithioic acid-3-oxo-1,3-diphenylpropyl ester (entry 5, Table 3):
Yield 460 mg; white solid; mp 125 °C; IR (KBr): 2956.5, 2366.9, 1677.9, 1432.4,
9. Bongar, B. P.; Sadavarte, V. S.; Uppalla, L. S. J. Chem. Res. (S) 2004, 9, 450.
10. (a) Blanrue, A.; Wilhelm, R. Synthesis 2009, 583; (b) Zhang, D.; Chen, J.; Liang,
Y.; Zhou, H. Synth. Commun. 2005, 35, 521.
1228.0, 1113.7, 978.7, 685.8 cmÀ1 1H NMR (CDCl3, 300 MHz): d 1.91–2.06 (m,
;
11. (a) Kanie, K.; Mizuno, K.; Kuroboshi, M.; Hiyama, T. Bull. Chem. Soc. Jpn. 1998,
71, 1973; (b) Halimehjani, A. Z.; Porshojaei, Y.; Saidi, M. R. Tetrahedron Lett.
2009, 50, 32; (c) Das, P.; Kumar, C. K.; Kumar, K. N.; Innus, M. D.; Iqbal, J.;
Srinivas, N. Tetrahedron Lett. 2008, 49, 992; (d) Wong, R.; Dolman, S. J. J. Org.
Chem. 2007, 72, 3969; (e) Guillaneuf, Y.; Couturier, J. L.; Gigmes, D.; Marque, S.
R. A.; Tordo, P.; Bertin, D. J. Org. Chem. 2008, 73, 4728; (f) Halimehjani, A. Z.;
4H), 3.56–3.62 (m, 2H), 3.70–3.79 (m, 1H), 3.92 (t, J = 6.75 Hz, 2H), 4.13 (dd,
J1 = 4.5 Hz and J2 = 4.5, 1H), 5.72–5.77 (m, 1H), 7.19–7.31 (m, 3H), 7.4–7.56 (m,
5H); 13C NMR (CDCl3, 75.5 MHz): d 24.2, 26.04, 45.1, 50.52, 50.61, 54.81,
127.59, 128.17, 128.35, 128.51, 128.55, 133.08, 136.6, 139.47, 191.20, 197.0;
Anal. Calcd for C20H21NOS2: C, 67.60; H, 5.91; N, 3.94. Found: C, 67.51; H, 6.02;
N, 3.88.