A high yielding, one-pot synthesis of S,S-dialkyl dithiocarbonates through the corresponding thiols using Mitsunobu's reagent

Article abstract of DOI:10.1007/BF03246060

A novel Mitsunobu-based technique has been developed for the synthesis of a variety of symmetrical and unsymmetrical S,Sdialkyl dithiocarbonates from various corresponding primary, secondary and tertiary thiols using gaseous carbon dioxide, in good to excellent yields.

Full text of DOI:10.1007/BF03246060

J. Iran. Chem. Soc., Vol. 7, No. 3, September 2010, pp. 702-706.
JOURNAL OF THE
Iranian
Chemical Society
A High Yielding, One-Pot Synthesis of S,S-Dialkyl Dithiocarbonates Through the
Corresponding Thiols Using Mitsunobu’s Reagent
A.K. Chaturvedia, D. Chaturvedib,*, N. Mishraa and V. Mishraa
aSynthetic Research Laboratory, Department of Chemistry, B. S. A. P. G. College, Mathura-281004, U. P., India
bBio-Organic Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi-180001, J. & K.,
India
(Received 9 August 2009, Accepted 29 October 2009)
A novel Mitsunobu-based technique has been developed for the synthesis of a variety of symmetrical and unsymmetrical S,S-
dialkyl dithiocarbonates from various corresponding primary, secondary and tertiary thiols using gaseous carbon dioxide, in good
to excellent yields.
Keywords: Synthesis, Dialkyl dithiocarbonates, Thiols, Carbon dioxide, Mitsunobu’s reagent
INTRODUCTION
associated with several drawbacks such as use of the costly,
toxic and corrosive reagents. Alternative routes for their
synthesis involves thermal [18], acid [19] or base [20]
catalyzed rearrangement of O,S-dialkyl dithiocarbonates to
S,S-dialkyl dithiocarbonates. Furthermore, various kinds of
Lewis acids [21] and phase transfer catalysts [22] were
Symmetrical
and
unsymmetrical
S,S-dialkyl
dithiocarbonates constitute an important and versatile class of
compounds for a variety of industrial, synthetic and medicinal
applications [1]. They have extensively been used as
pharmaceuticals [2], agrochemicals [3], intermediates in
organic synthesis [4] and in free radical polymerization
reactions [5] as solvent for rechargeable lithium ion batteries
[6] etc. Furthermore, their utility as a useful synthon for the
synthesis of various kinds of compounds such as ketones [7],
substituted ureas [8], alkane thiols [9], organic sulfides [10],
thiocarboxylic acids [11], alkane-sulfonyl chlorides [12],
thiolenes [13] and as coupling agent for esterification of
carboxylic acids [14] etc. all warrant their preparation through
a convenient and safe methodology.
employed
for
the
rearrangement
of
O,S-dialkyl
dithiocarbonates to S,S-dialkyl dithiocarbonates. Most of these
methods suffer from drawbacks such as long reaction times,
use of expensive strongly basic reagents, tedious work-up and
low yields. Consequently, there is continued interest in
developing new and convenient methods for the synthesis of
S,S-dialkyl dithiocarbonates using mild reaction conditions.
Our group [23] has been engaged for over several years on
the development of new, efficient and safer methods for the
synthesis of carbamates, dithiocarbamates, dithiocarbonates
(xanthates) using cheap and abundantly avaliable reagents like
CO2 and CS2. Recently, we reported [24] the synthesis of
carbamates, dithiocarbamates, carbonates, O,S-dialkyl
dithiocarbonates (xanthates), S-alkyl thiocarbamates and
trithiocarbonates from a variety of starting materials using
Classical synthesis of S,S-dialkyl dithiocarbonates involves
the reaction of thiols with phosgene [15], or its derivatives
[16], and carbon monoxide [17]. These reactions are
*Corresponding author. E-mail: ddchaturvedi002@yahoo.co.in

Chaturvedi et al.
Mitsunobu’s reagent. We report herein a chemoselective,
highly efficient and mild synthesis of symmetrical and
unsymmetrical S,S-dialkyl dithiocarbonates from a variety of
primary secondary, and tertiary thiols using Mitsunobu’s
reagent. We carried out the synthesis of S,S-dialkyl
dithiocarbonates by mild thiocarbonation of thiols with
gaseous carbon dioxide using various primary, secondary and
tertiary thiols mediated by Mitsunobu’s reagent at room
temperature. To the best of our knowledge, this is the first
report for the efficient and mild synthesis of S,S-dialkyl
dithiocarbonates starting from corresponding thiols using
Mitsunobu’s reagent.
S,S-Di-4-Methoxybenzyl dithiocarbonate (Entry 2): Oil;
1
IR (neat, cm-1): 2 = 1638, 878; H NMR ( 400 MHz, CDCl3):
1 = 3.83(s, 6H, OMe) 4.22 (s, 4H, SCH2Ph ), 7.07–7.25 (m,
10H, Ar-H); 13C NMR (100 MHz, CDCl3): 1 = 37.4, 56.2,
127.5, 128.5, 142.5, 202.2 (C=O) ppm; MS (m/z): 334;
HRMS: calcd. for C17H18O3S2: 334.07; found: 334.15.
RESULTS AND DISCUSSION
We assume that the unstable thiocarbonic acid 1, generated
from the reaction of thiol with carbon dioxide, reacts with
Mitsunobu’s zwitterion 2, formed from the Ph3P and diethyl
azadicarboxylate, to furnish the unstable ionic species 3
which, in turn, would undergo a self-rearrangement to form a
more stabilized ionic species 4. The nucleophilic attack of
sulfur atom of other thiols followed by intra-molecular
electronic rearrangement leads to the formation of the S,S-
dialkyl dithiocarbonate of the general formula I (see Schemes
1 and 2).
Thus, various primary, secondary and tertiary thiols were
made to react with Mitsunobu’s reagent/CO2 system to afford
S,S-dialkyl thiocarbonates in very good to excellent yields (82-
98%) at room temperature in 2-4 h. We tried many solvents
like DMSO, DMF, benzene, acetonirile, dichloromethane,
hexane, heptane, methanol, chloroform and acetone, whereby
dry DMSO was proved to be the most suitable solvent for
carring out this transformation.
In conclusion, we have developed a convenient and
efficient technique for one-pot, three-component coupling of
various thiols with a variety of primary, secondary and tertiary
thiols via Mitsunobu’s reagent/CO2 system. This reaction
generates the corresponding S,S-dialkyl dithiocarbonates in
excellent yields at room temperature. Furthermore, this
method exhibits substrate versatility, mild reaction conditions
and experimental convenience. This synthetic technique is
believed to offer a more general method for the formation of
C-S bonds essential for numerous organic syntheses.
EXPERIMENTAL
Chemicals were procured from Merck, Aldrich and Fluka
chemical companies. Reactions were carried out under Argon.
IR spectra 4000-200 cm-1 were recorded on Bomem MB-104-
FTIR spectrophotometer using neat technique, whereas NMRs
were scanned on an AC-300F, NMR (300 MHz), instrument
using CDCl3 and TMS as internal standard. Elemental analyses
were conducted by means of a Carlo-Erba EA 1110-CNNO-S
analyzer and agreed favorably with the calculated values.
General Experimental Procedure
Thiol (7.56 mmol) was taken in dry DMSO (25 ml) and
gaseous CO2 was bubbled through it for 30 min at room
temperature. To this, a mixture of triphenylphosphine (7.56
mmol) and diethyl azodicarboxylate (7.56 mmol) was added
slowly in 2-3 small portions. Next, the corresponding thiol
(7.56 mmol) was added with constant stirring at rt. The
reaction continued until completion (cf Table 1) as confirmed
by TLC. The reaction mixture was then poured into distilled
water (50 ml) and extracted with ethyl acetate thrice. The
organic layer was separated and dried over anhydrous sodium
sulphate and then concentrated to afford the desired S,S-
dialkyl dithiocarbonate.
S,S-Dibenzyl dithiocarbonate (Entry 1): Oil; IR (neat,
cm-1): 2 = 1640, 880; 1H NMR (400 MHz, CDCl3) 1 = 4.21 (s,
4H, SCH2Ph ), 7.06–7.24 (m, 10H, Ar-H); 13C NMR (100
MHz, CDCl3): 1 = 36.2, 126.9, 127.9, 128.5, 142.3, 200.5
(C=O) ppm; MS (m/z): 274; HRMS: calcd. for C15H14OS2:
274.05; found: 274.15.
ACKNOWLEDGENTS
The authors wish to thank SIAF division of the Indian
Institute of Integrative Medicine for providing spectroscopic
and analytical data.
703

A High Yielding, One-Pot Synthesis of S,S-Dialkyl Dithiocarbonates
O
R1
R3
R4
R6
R1
R3
R4
R6
Ph3P/DEAD, CO2, dry DMSO
R2
SH
R
SH
5
R2
S
+
S
R5
82-98%
RT, 2-4h,
I
Scheme 1
O
R1
R3
R1
R3
R2
SH
CO2
R2
S
1
+
OH
COOEt
Ph3P
N
N
2
3
COOEt
Ph3P
EtOOC N N COOEt
+
COOEt
H
Ph3P
R1
N
N
COOEt
1 + 2
O
R2
S
O
R3
H
H
EtOOC N N COOEt
O
O
R1
R1
COOEt
H
R4
R2
S
N
N
COOEt
O
PPh3
Ph PO
R2
S
S
R5
+
3
R3
R5
R3
R4
R6
I
4
SH
S, S-Dialkyl dithiocarbonate
R6
Scheme 2. Proposed mechanism of formation of S,S-dialkyl dithiocarbonates
Table 1. Conversion of Various Thiols into S,S-Dialkyl dithiocarbonates of General Formula Ia
Entry R1
R2
H
H
H
H
H
H
R3
R4
R5
H
H
H
H
H
H
R6
H
H
H
H
H
H
Time Yield
(h)
2.5
(%)b
91
1
2
3
4
5
6
Phenyl
H
Phenyl
H
4-Methoxyphenyl
4-Chlorophenyl
n-Butyl
4-Methoxyphenyl
2.5
3
93
86
94
95
96
H
H
H
H
4-Chlorophenyl
n-Butyl
n-Propyl
n-Octyl
2.5
2
n-Heptyl
n-Octyl
2
704

Chaturvedi et al.
Table 1. Continued
7
Phenyl
Methyl
n-Butyl
n-Butyl
H
H
H
n-Hexyl
4-Methoxyphenyl
H
H
2.5
3
91
86
83
94
94
90
91
82
86
9
n-Butyl
H
H
10
11
12
13
14
15
16
n-Butyl
n-Butyl n-Octyl
H
H
3.5
2.5
2
n-Hexyl
H
H
H
H
Benzyl
H
H
n-Heptyl
n-Octyl
Me
n-Heptyl
Phenethyl
n-Butyl
H
H
H
H
H
2.5
2.5
4
n-Heptyl
n-Pentyl
H
n-Butyl
n-Butyl
H
H
Methyl
H
n-Butyl n-Butyl
n-Butyl
2-Naphthyloxyethyl
H
n-Octyl
H
2.5
17
18
3-(2-Naphthyloxy)prop-1-yl
H
H
n-Dodecyl
H
H
H
H
2
3
95
88
n-Hexyl
Me
Me
Benzyl
19
n-Decyl
H
H
n-Heptyl
H
H
2
98
aAll the products were characterized by IR, NMR and mass spectral data. bIsolated yields.
REFERENCES
[4] a) J. Crosby, K.J. Grant, D.J. Greig, R.M. Paton, R.G.
Rankin, J.F. Ross, ARKIVOC (2002) 121; b) M.
Barbero, S. Cadamuro, I. Degani, R. Fochi, V. Regondi,
Synthesis (1989) 957; c) D. Witt, R. Klajn, P. Barski,
B.A. Grzybowski, Curr. Org. Chem. 8 (2004) 1763.
[5] a) L. Benati, R. Learndini, M. Minozzi, D. Nanni, R.
Scialpi, P. Spagnolo, S. Strazzari, G. Zanardi, Angew.
Chem. Int. Ed. 116 (2004) 3682; b) B. Quiclet-Sire,
S.Z. Zard, Top. Current Chem. (2006) 201.
[1] a) K. Yoshida, K. Kosegaki, Makromol. Chem. 161
(1972) 267; b) E. Reid, Organic Chemistry of Bivalent
Sulfur, Vol. 4, Chemical Publishing Co. New York,
1962, p. 170 and references cited therein.
[2] a) H. Foks, J. Mieczkowska, M. Janowiec, Z. Zwolska,
Z. Andrzejczyk, Chemistry of Heterocyclic Compounds
38 (2002) 810; b) F. Dehmel, T. Ciossek, T. Maier, S.
Weinbrenner, B. Schmidt, M. Zoche, T. Beckers, Bio-
Org. Med. Chem. Lett. 17 (2007) 4746.
[6] a) Y. Ein-Eli, S.F. McDevitt,
J. Solid State
Electrochem. 1 (1997) 227; b) S.J. Santner, K.C.
Moller, M.G. Ramsey, F.P. Netzer, S. Yamaguchi, J.O.
Besenhard, W. Winter, J. Power Sources 119-121
(2003) 368.
[3] H. Elster, W. Hahn, K. Goliasch, W. Behrenz, German
Patent (DOS) a) 1207140, 1965; b) H. Jindal, A.
Fischer, German Patent (DOS) 1950433, 1971.
705

A High Yielding, One-Pot Synthesis of S,S-Dialkyl Dithiocarbonates
[7] a) C.D. Chen, J.W. Huang, M.K. Leung, H.S. Li,
576.
Tetrahedron 54 (1998) 9067; b) C. Cardilliccio, V.
Fiandanese, G. Marchese, L. Ronzini, Tetrahedron Lett.
26 (1988) 3595; c) B.F. Bonini, C.M. Capperuci, A.
Degllnnocent, G. Mazzanti, A. Ricci, P. Zani, Synlett
(1993) 937.
M.K. Leung, J.L. Lai, K.H. Lan, Y.H. Yu, H.J. Hsiao,
J. Org. Chem. 61 (1996) 4179.
a) I. Degani, R. Fochi, V. Regondi, Synthesis (1983)
630; b) I. Degani, R. Fochi, V. Regondi, Chem. Ind.
(1986) 671; c) S. Cacamuro, I. Degani, R. Fochi, V.
Regondi, Synthesis (1986) 1073.
[22] I. Degani, R. Fochi, V. Regondi, Synthesis (1980) 375;
b) I. Degani, R. Fochi, V. Regondi, Synthesis (1981)
149.
[23] For reviews see: a) D. Chaturvedi, S. Ray, Curr. Org.
Chem. 11 (2007) 987; b) D. Chaturvedi, N. Mishra, V.
Mishra, Curr. Org. Synthesis 3 (2007) 308; For our
research work see: c) D. Chaturvedi, A. Kumar, S. Ray,
Synth. Commun. 32 (2002) 2651; d) D. Chaturvedi, S.
Ray, Lett. Org. Chem. 2 (2005) 742; e) D. Chaturvedi,
S. Ray, J. Sulfur Chem. 26 (2005) 365; f) D.
Chaturvedi, S. Ray, J. Sulfur Chem. 27 (2006) 265; g)
D. Chaturvedi, S. Ray, Monatsh. Chem. 137 (2006)
201; h) D. Chaturvedi, S. Ray, Monatsh. Chem. 137
(2006) 311; i) D. Chaturvedi, S. Ray, Monatsh. Chem.
137 (2006) 459; j) D. Chaturvedi, S. Ray, Monatsh.
Chem. 137 (2006) 465; k) D. Chaturvedi, S. Ray,
Monatsh. Chem. 137 (2006) 1219 ; l) D. Chaturvedi, N.
Mishra, V. Mishra, J. Sulfur Chem. 28 (2007) 39; m) D.
Chaturvedi, N. Mishra, V. Mishra, J. Sulfur Chem. 28
(2007) 607; n) D. Chaturvedi, N. Mishra, V. Mishra,
Monatsh. Chem. 139 (2008) 267; o) D. Chaturvedi,
A.K. Chaturvedi, N. Mishra, V. Mishra, Synth.
Commun. 38 (2008) 4013; p) D. Chaturvedi, N. Mishra,
A.K. Chaturvedi, V. Mishra, Synth. Commun. 39
(2009) 1273; q) D. Chaturvedi, A.K. Chaturvedi, N.
Mishra, V. Mishra, J. Iran. Chem. Soc. 6 (2009) 510.
[24] a) D. Chaturvedi, A. Kumar, S. Ray, Tetrahedron Lett.
44 (2003) 7637; b) D. Chaturvedi, S. Ray, Tetrahedron
Lett. 47 (2006) 1307; c) D. Chaturvedi, S. Ray,
Tetrahedron Lett. 48 (2007) 149; d) D. Chaturvedi, N.
Mishra, V. Mishra, Tetrahedron Lett. 48 (2007) 5043;
e) D. Chaturvedi, N. Mishra, V. Mishra, Synthesis
(2008) 355; f) D. Chaturvedi, A.K. Chaturvedi, N.
Mishra, V. Mishra, Tetrahedron Lett. 49 (2008) 4886.
[8]
[9]
[10] I. Degani, R. Fochi, V. Regondi, Synthesis (1979) 178.
[11] S. Cadzurao, I. Degani, R. Fochi, V. Regondi, Synthesis
(1986) 1070.
[12] M. Barbero, S. Cadamuro, I. Degani, R. Fochi, V.
Regondi, Synthesis (1989) 957.
[13] a) X. Yang, G.K.W. Freeman, T.B. Rauchfuss, S.R.
Wilson, Inorg. Chem. 30 (1991) 3034; b) S.B. Wilkes,
I.R. Butler, A.E. Underhill, A. Kobayashi, H.
Kobayashi, J. Chem. Soc. Chem. Commun. (1994) 53.
[14] S. Kim, S. S. Kim, Synthesis (1986) 1017.
[15] I. Degani, R. Fochi, V. Regondi, Synthesis (1975) 375.
[16] H. Ester, E. Muhlbauer, German Patent (DBP)
1181205, (1965).
[17] T. Mizuno, T. Yamaguchi, I. Nishiguchi, T. Okushi, T.
Hirashima, Chem. Lett. (1990) 811.
[18] K. Harano, T. Taguchi, Chem. Pharm. Bull. 20 (1972)
2357.
[19] T. Kirata, K. Harano, Yakugaku Zasshi. 76 (1976) 832.
[20] Y. Yoshida, Bull. Chem. Soc. Jpn. 42 (1969) 1948.
[21] a) K. Komaki, T. Kowata, K. Harano, T. Taguchi,
Chem. Pharm. Bull. 26 (1978) 3807; b) T. Kowata, K.
Harano, T. Taguchi, Chem. Pharm. Bull. 21 (1973)
604; c) K. Harano, I. Shinohara, S.I. Sugumoto, T.
Matsuoka, T. Hisano, Chem. Pharm. Bull. 37 (1989)
706