An efficient synthesis of dithiocarbamates under ultrasound irradiation in water

Article abstract of DOI:10.1007/s00706-011-0687-z

Multicomponent reactions with ultrasonic activation have been used as a simple, rapid, atom economic, and green method for the synthesis of dithiocarbamate derivatives in water. The one-pot, three-component condensation of primary and secondary amines with carbon disulfide and unsaturated carbonyl compounds or alkyl halides under ultrasonic irradiation was developed as a green and fast protocol for the rapid high-yielding preparation of dithio-carbamates in water.

Full text of DOI:10.1007/s00706-011-0687-z

Monatsh Chem (2012) 143:1171–1174
DOI 10.1007/s00706-011-0687-z
ORIGINAL PAPER
An efficient synthesis of dithiocarbamates under ultrasound
irradiation in water
•
Najmadin Azizi Elahm Gholibeglo
•
Sanaz Dehghan Nayeri
Received: 11 June 2011 / Accepted: 5 November 2011 / Published online: 29 November 2011
Ó Springer-Verlag 2011
Abstract Multicomponent reactions with ultrasonic acti-
vation have been used as a simple, rapid, atom economic, and
green method for the synthesis of dithiocarbamate deriva-
tives in water. The one-pot, three-component condensation
of primary and secondary amines with carbon disulfide and
unsaturated carbonyl compounds or alkyl halides under
ultrasonic irradiation was developed as a green and fast
protocol for the rapid high-yielding preparation of dithio-
carbamates in water.
selectivities, enhancing product recovery, and minimizing
the production of waste at source. On the other hand,
ultrasound is widely used for improving the traditional
reactions that involve expensive reagents, strongly acidic
conditions, long reaction times, high temperatures, unsat-
isfactory yields, and incompatibility with other functional
groups [6–9].
Organic dithiocarbamates are valuable synthetic inter-
mediates which are found in a variety of biologically active
compounds [10]. Functionalization of the carbamate moi-
ety offers an attractive method for the generation of
derivatives, which may have interesting medicinal and
biological properties [11]. For these reasons, the synthesis
of dithiocarbamate derivatives with different substitution
patterns at the thiol chain has become a field of increasing
interest in synthetic organic chemistry during the past few
years.
Keywords Carbon disulfide Á Dithiocarbamate Á
Multicomponent reaction Á Water chemistry Á
Ultrasonic irradiation
Introduction
Most chemical manufacturing industries and chemistry
laboratories use electricity generated from coal for heating
purposes and organic solvents which are responsible for
environmental pollution. In view of this, attempts have
been made to use alternate energy sources and green
reaction media in organic synthesis and industry. In this
context the use of water as an alternate greener reaction
medium [1–5] has gained popularity, offering environ-
mentally clean technology by improving product yields and
Among the numerous methods for the synthesis of
dithiocarbamate derivatives, condensation of amines with
isothiocyanate, thiophosgene, or its derivatives constitutes
the most widely accepted general method [12, 13]. Despite
the toxicity of these reagents, their use remains inevitable
because of the importance of dithiocarbamates in the biolo-
gical field and organic synthesis. Therefore, safer, nontoxic,
and user-friendly one-pot procedures for the synthesis of
dithiocarbamates have been developed recently [14–31].
Results and discussion
N. Azizi (&) Á E. Gholibeglo
Chemistry and Chemical Engineering Research Center of Iran,
P.O. Box 14335-186, Tehran, Iran
e-mail: azizi@ccerci.ac.ir
During the course of our study aimed at improving the eco-
compatibility of certain organic processes, we have been
particularly interested in the synthesis of dithiocarbamates
in water and solvent-free conditions to develop environ-
mentally benign reactions [32–37]. Herein, we wish to
S. D. Nayeri
Department of Chemistry, Islamic Azad University,
Shahr-e-Rey Branch, Tehran, Iran
123

1172
N. Azizi et al.
report an efficient preparation of dithiocarbamate deriva-
tives from the one-pot reaction of amines, carbon disulfide,
and unsaturated enones or alkyl halides in water under
ultrasound irradiation.
First, we embarked upon a series of experiments to
establish the optimum conditions. First findings showed
that the three-component reaction of 2 mmol pyrrolidine
with 2 mmol methyl acrylate and 3 mmol carbon disulfide
in 2 cm3 water under ultrasound irradiation for 10 min was
an excellent reaction condition and dithiocarbamate 3 was
obtained in 90% yield (Scheme 1).
S
O
H
N
With the optimal reaction conditions in hand, we
investigated the generality and scope of the one-pot, three-
component reaction with a variety of aliphatic amines and
various electron-deficient olefins. A variety of a,b-unsatu-
rated compounds such as methyl acrylate, acrylonitrile,
O
CS2, water, )))))
10 min, 90%
+
N
S
OMe
OMe
3
1
2
Scheme 1
Table 1 Ultrasound-assisted, one-pot preparation of dithiocarbamates in water
S
R"
CS2, water
X
X
+
RR'NH
R"
RR'N
S
))))), 10 min
60-95%
1
2
3
X = COOMe, COMe, CN
CH2NH2
NH2
H
N
H
N
H
N
NH2
H2N
NH
1a
1b
1c
1d
1e
1f
1g
1h
Entry
Michael acceptor
Amine
Yielda/%
Ref.
1
Methyl acrylate
Methyl acrylate
Methyl acrylate
Methyl acrylate
Methyl acrylate
Methyl acrylate
Acrylonitrile
1a
1b
1c
1d
1f
88
90
90
80
75
78
90
88
80
75
78
95
88
85
92
74
68
78
76
70
[15]
[15]
[16]
[16]
[18]
[18]
[18]
[18]
[18]
[15]
[20]
[18]
[18]
[15]
[18]
[15]
[18]
[18]
[15]
[18]
2
3
4
5
6
1g
1a
1b
1c
1d
1h
1a
1b
1d
1e
1a
1b
1c
1b
1c
7
8
Acrylonitrile
9
Acrylonitrile
10
11
12
13
14
15
16b
17b
18b
19
20
a
Acrylonitrile
Acrylonitrile
Methyl vinyl ketone
Methyl vinyl ketone
Methyl vinyl ketone
Methyl vinyl ketone
Benzylideneacetone
Benzylideneacetone
Benzylideneacetone
Methyl methacrylate
Methyl methacrylate
Isolated yields
b
Reaction time 15 min
123

An efficient synthesis of dithiocarbamates
1173
methyl vinyl ketone, methyl methacrylate, and benzyli-
deneacetone underwent 1,4-addition with a wide range of
aliphatic amines like n-butylamine, benzylamine, pyrroli-
dine, piperidine, dipropylamine, and diethylamine to give
the corresponding dithiocarbamates in high yields. The
results are summarized in Table 1. In general, all the
syntheses were performed under mild reaction conditions
and showed short reaction times, good selectivity, and the
absence of by-products.
We next examined the feasibility of utilizing the current
strategy for the one-pot synthesis of dithiocarbamates from
amines, carbon disulfide, and alkyl halides under the same
reaction conditions (Scheme 2). In fact, treatment of a wide
variety of alkyl halides with aliphatic amines and carbon
disulfide at room temperature affords satisfactory to good
yields of a variety of dithiocarbamates 5, mainly in very
short reaction times (10 min). The results are summarized
in Table 2. Alkyl chlorides, bromides, and iodides are
equally effective and no marked difference was observed in
terms of reaction time and yield.
S
CS2, water, )))))
+
R"
X
RR'NH
RR'N
R"
S
10 min
1
4
5
Scheme 2
Table 2 Ultrasound-assisted, one-pot reaction of amines, carbon disulfide, and alkyl halides in water
S
R"
CS2, water
+
RR'NH
R"
X
RR'N
NH2
S
5
))))))), 10 min
64-90%
1
4
X = I, Br, Cl
CH2NH2
NH2
H
N
H
N
H
N
H2N
NH
1a
1b
1c
1d
1f
1g
1e
1h
Entry
Alkyl halide
Amine
Yielda/%
Ref.
1
Benzyl chloride
Benzyl chloride
Benzyl chloride
Benzyl chloride
Benzyl chloride
Benzyl chloride
1a
1b
1c
1f
80
84
90
76
72
70
85
80
88
76
68
74
72
80
64
92
80
84
86
80
[15]
[19]
[19]
[15]
[19]
[23]
[23]
[19]
[19]
[14]
[19]
[15]
[15]
[14]
[15]
[30]
[22]
[22]
[19]
[19]
2
3
4
5
1g
1h
1a
1b
1c
1d
1e
1a
1b
1c
1d
1a
1b
1c
1b
1c
6
7
3-Chlorobenzyl chloride
3-Chlorobenzyl chloride
3-Chlorobenzyl chloride
3-Chlorobenzyl chloride
3-Chlorobenzyl chloride
Allyl chloride
8
9
10
11
12
13
14
15
16
17
18
19
20
a
Allyl chloride
Allyl chloride
Allyl chloride
Methyl bromoacetate
Methyl bromoacetate
Methyl bromoacetate
Methyl iodide
Methyl iodide
Isolated yields
123

1174
N. Azizi et al.
References
In summary, we have developed a mild and fast pro-
cedure for the synthesis of various dithiocarbamates with
excellent yields in water under ultrasonic irradiation. This
simple procedure is greener and less laborious in terms of
isolation and purification than those using isothiocyanates.
Furthermore, the ultrasound-assisted procedure requires
short reaction times, is catalyst-free, low cost, and affords
efficient selectivity, which makes this method a useful and
attractive strategy in view of economic and environmental
advantages.
1. Parikh N, Kumar D, Roy SR, Chakraborti AK (2011) Chem
Commun 47:1797
2. Sharma G, Kumar R, Chakraborti AK (2008) Tetrahedron Lett
49:4269
3. Chakraborti AK, Rudrawar S, Jadhav KB, Kaur G, Chankeshwara
SV (2007) Green Chem 9:1335
4. Chankeshwara SV, Chakraborti AK (2006) Org Lett 8:3259
5. Khatik GL, Kumar R, Chakraborti AK (2006) Org Lett 8:2433
6. Rajagopal R, Jarikote DV, Srinivasan KV (2002) Chem Commun 616
7. Song BA, Zhang GP, Yang S, Hu DY, Jin LH (2001) Ultrason
Sonochem 13:139
8. Mason TJ (1997) Chem Soc Rev 26:443
9. Mawson R, Gamage M, Shiferaw Terefe N, Knoerzer K (2011)
Food Eng 369
Experimental
10. Brooks GT (1989) In: Sulfur Containing Drugs and Related
Organic Compounds: Chemistry, Biochemistry, and Toxicology,
vol. 1, part A. Damani LA (ed). Ellis Horwood, Chichester, p 62
11. Aitken RA, Wilson NJ (1998) J Sulfur Chem 21:81
12. Tilles H (1959) J Am Chem Soc 81:714
13. Elgemeie GH, Sayed SH (2001) Synthesis 1747
14. Chaturvedi D, Ray S (2007) Tetrahedron Lett 48:149
15. Ranu BC, Saha A, Banerjee SE (2008) J Org Chem 73:519
16. Azizi N, Ebrahimi F, Aakbari E, Aryanasab F, Saidi MR (2007)
Synlett 2797
17. Xia S, Li RT, Wang X, Ge Z, Cheng T (2009) Tetrahedron 65:1005
18. Azizi N, Aryanasab F, Torkiyan L, Ziyaei A, Saidi MR (2006) J
Org Chem 71:3634
19. Azizi N, Aryanasab F, Saidi MR (2006) Org Lett 8:5275
20. Lal N, Kumar L, Sarswat A, Jangir S, Sharma VL (2011) Org Lett
13:2330
1H NMR spectra (500 MHz) and 13C NMR spectra
(125 MHz) were recorded using CDCl3 or DMSO-d6 as
solvents. Chemical shifts are expressed in ppm downfield
from TMS. Melting points were recorded on a Bu¨chi 535
melting point apparatus. All starting materials are com-
mercially available and were used without further
purification. Water and other solvents were distilled before
used. Sonication was performed in a Hielscher ultrasonic
device (Vial Tweeter at UIS250v) with Sonotrode LS24d5
and Ampitude 80.
General procedure
21. Alizadeh A, Rostamnia S, Zohreh N, Hosseinpour R (2009)
Tetrahedron Lett 50:1533
A mixture of 0.16 cm3 pyrrolidine (2 mmol), 0.18 cm3
carbon disulfide (3 mmol), and 0.18 cm3 methyl propeno-
ate (2 mmol) in 2 cm3 water was sonicated at room
temperature for 10 min in a beaker surrounded by a water
bath for cooling. The reaction mixture was allowed to stand
for 10 min at room temperature and then the solid dithio-
carbamate product was collected, washed with ethanol or
diethyl ether, and dried in air. The reaction products were
obtained in high purity in most cases, and did not require
further purification by recrystallization or column chro-
matography. In a few cases the aqueous mixture was
extracted with 10 cm3 diethyl ether or ethyl acetate, dried
over anhydrous Na2SO4, and the solvent was removed
under reduce pressure to give the desired products. All
22. Azizi N, Aryanasab F, Torkiyan L, Saidi MR (2011) Synth
Commun 41:94
23. Chaturvedi D, Ray S (2006) Tetrahedron Lett 47:1307
24. Chaturvedi D, Ray S (2006) Monatsh Chem 137:311
25. Chaturvedi D, Mishra N, Mishra V (2008) Synthesis 355
26. Chaturvedi D, Ray S (2005) J Sulfur Chem 26:365
27. Chaturvedi D, Mishra N, Mishra V (2007) J Sulfur Chem 28:39
28. Chaturvedi D, Ray S (2007) Tetrahedron Lett 48:149
29. Yadav LDS, Patel R, Srivastava VP (2009) Tetrahedron Lett
50:1335
30. Goubert-Renaudin S, Schneider R, Walcarius A (2007) Tetrahe-
dron Lett 48:2113
31. Salvatore RN, Sahaba S, Junga KW (2001) Tetrahedron Lett
42:2055
32. Azizi N, Saidi MR (2004) Organomet 23:1457
33. Azizi N, Saidi MR (2005) Org Lett 7:3649
34. Azizi N, Aryanasab F, Saidi MR (2006) Org Biomol Chem
4:4275
35. Azizi N, Baghi R, Ghafuri H, Bolourtchian M, Hashemi M (2010)
Synlett 379
1
compounds are known and IR and H NMR spectra were
found to be identical to those described in Refs. [14–31].
36. Azizi N, Torkiyan L, Saidi MR (2006) Org Lett 8:2079
37. Azizi N, Khajeh-Amiri A, Ghafuri H, Bolourtchian M (2011) Mol
Divers 15:157
Acknowledgments Financial support of this work by Chemistry
and Chemical Research Center of Iran is gratefully appreciated.
123