An efficient transesterification of β-oxodithioesters catalyzed by stannous chloride under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2013.01.001

Transesterification of β-oxodithioesters catalyzed by stannous chloride under solvent-free condition has been reported for the first time. The short reaction time and good to excellent yields using inexpensive catalysts are attractive features of this synthetic protocol. Copyright

Full text of DOI:10.1016/j.tetlet.2013.01.001

Tetrahedron Letters 54 (2013) 1432–1435
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An efficient transesterification of b-oxodithioesters catalyzed by stannous
chloride under solvent-free conditions
⇑
Nepram Sushuma Devi , Sarangthem Joychandra Singh, Okram Mukherjee Singh
Department of Chemistry, Manipur University, Canchipur 795003, Manipur, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Transesterification of b-oxodithioesters catalyzed by stannous chloride under solvent-free condition has
been reported for the first time. The short reaction time and good to excellent yields using inexpensive
catalysts are attractive features of this synthetic protocol.
Received 2 October 2012
Revised 29 December 2012
Accepted 1 January 2013
Available online 9 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Alcohols
b-Oxodithioesters
Transesterification
Solvent-free
Stannous chloride
S
The toxicity and volatile nature of many organic solvents, par-
ticularly chlorinated hydrocarbons that are widely used in huge
amounts for organic reactions have posed a serious threat to the
environment. Designing of efficient chemical transformation in a
single operation by a catalytic process avoiding stoichiometric
toxic reagents, large amounts of solvents, and expensive
purification techniques represents a fundamental target of the
green chemistry.1 Thus, the design of solvent-less catalytic reaction
has received tremendous attention in recent times in the area of
green synthesis.2,3 This prompted us to initiate a systematic inves-
tigation to look into the feasibility of solvent-free reactions toward
the development of green methodology for biologically useful
molecules.
r.t.
3-4h
Na2S
CS2
(CH3)2SO4
+
+
MeS
CH3
SMe
2
1
4
3
O
NaH
DMF/Hexane
R1/Ar
5a-f
O
S
R1/Ar
SMe
6a-f
Scheme 1. Synthesis of b-oxodithioesters.
The transesterification is an important synthetic process used as
an alternative method to synthesize various carboxylic esters. The
transesterification of b-ketoesters has been found to be a very use-
ful tool in organic synthesis having wide applications in academic
as well as industrial research. b-Ketoesters are employed widely as
chemical intermediates in the pharmaceutical, agrichemical,
chemical, and polymer industries.4 The electrophilic and nucleo-
philic sites of b-ketoesters make them a valuable tool for the syn-
thesis of complex natural products,5a such as paclitaxel,5b
podophyllotoxin,5c serricornine,5d trichodiene,5e karrikinolide
(KAR1), and tetrahydrozerumbone.5f The chelate complex of b-
ketoesters suppresses the activity of some pathogenic viruses
through the formation of a coordinate bond to metal ions at the
active site of the virus enzyme responsible for virus replication.6
The transesterification is an important organic transformation
and provides essential synthons for pheromones and additives
for paints.7 In addition, this reaction is an essential part of the man-
ufacturing process of polyethylene terephthalate.8
A number of useful and reliable esterification methods cata-
lyzed by a variety of reagents such as DMAP,9a DBU,9b titanium tet-
raalkoxide,9c tetrabutyl distannoxanes,9d,e p-TSA,9f indium
triiodide,9g iodotrimethylsilane/I2,9h iodine,9i BiCl3,9j zeolite H-
FER,9k and Yb(OTf)39l have been well documented for transesterifi-
cation. Recent developments include variation and improvements
of well established procedures and the discovery and application
of new reagents.9j–l
A careful literature survey reveals that there have been no re-
ports on the transesterification of b-oxodithioesters. The existing
⇑
Corresponding author. Tel./fax: +91 0385 2435145.
E-mail address: nsushuma@gmail.com (N.S. Devi).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.01.001

N. S. Devi et al. / Tetrahedron Letters 54 (2013) 1432–1435
1433
Table 1
Synthesis of b-oxodithioesters
The desired b-oxodithioesters 6a–f are obtained by treating ac-
tive methylene compounds 5 with (S,S)-dimethyl trithiocarbonate
411 in the presence of NaH (Scheme 1, Table 1).
Entry
1
Ar/R1
Dithioesters
Yielda (%)
72
The transesterification reaction of easily accessible b-oxodithio-
esters 6a (1 mmol) with benzyl alcohol 7a (1 mmol) was studied in
the presence of 5 mol % SnCl2 as a model reaction (Table 2, entry 1).
After completion of the reaction (monitored by TLC), the catalysts
were filtered, and the filtrate was concentrated to get a crude prod-
uct which was purified by column chromatography using ethyl
acetate and petroleum ether to give the desired transesterified
product 8a as a viscous pale yellow liquid (Scheme 2). The reaction
smoothly proceeded in the solvent-free condition to give transe-
sterified product 8a in 80% yield in 1 h. The formation of compound
8a was confirmed by the spectral and analytical data.
The model reaction was also tried with different catalysts such
as CuCl2, ZnCl2, AlCl3, and FeCl3 (Table 2). However, the use of these
catalysts cannot improve the yield of the reaction. An increase in
the catalyst showed no substantial improvement in the yield,
though a slight improvement in the reaction time was observed.
Thus, the reaction was optimized with the use of 5 mol % of
SnCl2Á2H2O.
O
S
(6a)
SMe
S
O
CH3
OCH3
Cl
(6b)
SMe
2
75
H3C
H3CO
Cl
O
S
SMe
3
4
(6c) 73
O
S
SMe
71
(6d)
O
S
5
6
CH3
50
61
(6e)
H3C
S
SMe
Under these optimized conditions, various b-oxodithioesters
6b–f underwent a smooth transesterification with various alcohols
like benzyl alcohol, n-butanol, isopropanol, and tertiary butyl alco-
hol giving good yields of transesterification products (Table 3).
A noteworthy merit of the present protocol is that a variety of
structurally different alkyl/aryl/heteroaryl b-oxodithioesters
underwent the smooth transesterification with various alcohols.
In all the cases, 5 mol % of the catalyst can effectively catalyze
the reaction to completion. The role of the catalyst is probably to
increase the electrophilicity of thiocarbonyl carbon to facilitate
the nucleophilic attack of the alcoholic OH group.
S
O
S
SMe
(6f)
a
Yield of isolated product.
Table 2
Optimization of catalyst on model reactiona
Entry
Catalyst
Mol %b
Time (min)
Yieldc (%)
As seen from Table 3, the esterification reaction proceeds
smoothly with primary, secondary, and tertiary alcohols with the
reactivity of the alcohols decreasing in the order primary > second-
ary > tertiary. The yields of the products also showed a trend in the
same order as that of the reactivity. Esters of tertiary alcohols
which are difficult to prepare are obtained in moderate yields
due to steric hindrance. It is noteworthy to mention that phenol,
p-cresol, and m-chlorophenol failed to undergo transesterification
due to low reactivity.
1
2
3
4
5
6
7
8
SnCl2
SnCl2
SnCl2
FeCl3
ZnCl2
CuCl2
AlCl3
None
5
10
15
15
25
20
15
—
60
40
35
30
40
50
30
30
80
75
73
55
61
57
62
Nil
a
Reaction conditions: acetophenone dithioester (1 mmol), benzyl alcohol
(1 mmol) under neat condition at 110 °C.
The structure of all the products was characterized by IR, 1H
b
Amount of catalyst used based on 7a.
Isolated yield based on 7a.
NMR, 13C NMR, CHN analysis, and mass spectrometry.12
c
In conclusion, we have successfully demonstrated the transe-
sterification of b-oxodithioesters in the presence of a catalytic
amount of stannous chloride under solvent-free condition. The
short reaction time, mild reaction condition, and good to excellent
yields using inexpensive catalysts are attractive features of this
protocol. We believe that transesterification products of b-oxodi-
thioesters will provide an essential synthons for asymmetric Man-
nich reactions with acyl imines. Further, the products from the
Mannich reaction will be of use in the synthesis of highly biologi-
cally active enantioenriched dihydropyrimidones and b-amino
alcohols. Besides this, they may be employed for the production
of chiral alcohols by reduction.
methods involve the esterification of only b-ketoesters such as
methyl acetoacetate and ethyl acetoacetate and variations de-
signed in the structures of alcohol yielding an esterification
product either in improved yield or by the application of new
methodologies are always reported. During the course of our stud-
ies on the synthetic application of b-oxodithioesters in various or-
ganic transformations,10a–d we report herein a novel and efficient
method for facile transesterification of b-oxodithioesters using
stannous chloride under solvent-free conditions.
O
S
O
S
110oC
SnCl2.2H2O
HO
O
SMe
+
6a
8a
7a
Scheme 2. Esterification of acetophenone dithioester with benzyl alcohol as model reaction.

1434
N. S. Devi et al. / Tetrahedron Letters 54 (2013) 1432–1435
Table 3
Transesterification of b-oxodithioesters with various alcohols
O
R1/Ar
S
O
S
SnCl2.2H2O
110oC,1-2 h
R2OH
7a-d
SMe
R1/Ar
OR2
+
6a-f
8a-m
Entry
1
Dithioesters
Alcohols
Product
Yielda (%)
80
O
S
O
S
OH
SMe
S
O
8a
O
O
S
OH
OH
SMe
O
2
3
83
85
H3C
H3C
8b
S
O
S
O
SMe
O
H3CO
H3CO
8c
O
S
O
S
OH
OH
OH
SMe
O
4
5
6
77
75
79
Cl
Cl
8d
O
S
O
S
H3C
S
SMe
S
H3C
O
8e
S
O
O
S
O
SMe
8f
O
S
O
S
OH
OH
O
SMe
7
8
75
79
8g
O
O
S
S
O
SMe
H3C
H3C
8h
O
S
O
S
OH
OH
SMe
O
9
80
77
H3CO
Cl
H3CO
Cl
8i
S
O
S
O
O
S
SMe
10
8j
O
O
S
O
O
S
OH
OH
SMe
O
11
73
8k
O
S
O
SMe
O
12
13
69
51
H3CO
H3CO
8l
S
S
OH
O
SMe
8m
a
Yield of isolated product.

N. S. Devi et al. / Tetrahedron Letters 54 (2013) 1432–1435
1435
10. (a) Singh, O. M.; Devi, N. S. J. Org. Chem. 2009, 74, 3141–3144; (b) Singh, O. M.;
Devi, N. S.; Thokchom, D. S.; Sharma, G. J. Eur. J. Med. Chem. 2010, 45, 2250–
2257; (c) Singh, O. M.; Devi, N. S.; Devi, L. R.; Lim, K. B.; Yoon, Y. J.; Lee, S-G. Bull.
Korean Chem. Soc. 2011, 32, 175–178; (d) Devi, N. S.; Singh, S. J.; Devi, L. R.;
Singh, O. M. Tetrahedron Lett. 2013, 54, 183–187.
Acknowledgments
The authors are thankful to SAIF, NEHU, Shillong and SAIF, CDRI
Lucknow for spectral recording. OMS is grateful to CSIR (New Del-
hi) for financial assistance. S.J.S. is also thankful to UGC, New Delhi
for D. S. Kothari Post Doctoral Fellowship.
11. Wood, M. R.; Duncalf, D. J.; Rannard, S. P.; Perrier, N. S. Org. Lett. 2006, 8, 553–
556.
12. General procedure for the synthesis of propanethioate (5a–m): a mixture of b-
oxodithioesters (1 mmol), alcohol (1 mmol), and 5 mol% SnCl2Á2H2O was
heated at 110 °C in
a round bottom flask provided with a distillation
References and notes
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O-Benzyl 3-oxo-3-phenylpropanethioate (8a): viscous pale yellow liquid, 1H
NMR (CDCl3, 400 MHz): d 4.09 (s, 2H), 5.25 (s, 2H), 7.29–7.31 (m, 5H), 7.85 (m,
3H), 7.31 (d, J = 8 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d 46.2, 69.7, 128.1, 128.3,
128.5, 129.7, 129.9, 135.6, 136.5, 145.5, 167.9, 192.3; IR (KBr) (m
max, cmÀ1):
1715, 1687; EI MS (m/z): 270 (M+). Anal. Calcd for C16H14O2S: C, 71.08; H, 5.22;
S, 11.86. Found: C, 71.15; H, 5.17; S, 11.83.
O-Benzyl 3-oxo-3-p-tolylpropanethioate (8b): viscous pale yellow liquid, 1H
NMR (CDCl3, 400 MHz): d 2.41 (s, 3H), 4.05 (s, 2H), 5.20 (s, 2H), 7.25 (d, J = 8 Hz,
2H), 7.33–7.35 (m, 5H), 7.82 (d, J = 8 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d 25.3,
46.1, 69.9, 128.2, 128.5, 128.7, 129.5, 129.9, 135.5, 136.9, 145.7, 167.7, 192.7;
IR (KBr) (m
max, cmÀ1): 1717, 1690; EI MS (m/z): 284 (M+). Anal. Calcd for
C
17H16O2S: C, 71.80; H, 5.67; S, 11.28. Found: C, 71.87; H, 5.63; S, 11.25.
O-Butyl 3-oxo-3-phenylpropanethioate (8g): viscous pale yellow liquid, 1H NMR
(CDCl3, 400 MHz): d 0.88 (t, J = 7.4 Hz, 3H), 1.28–1.34 (m, 2H), 1.55–1.60 (m,
2H), 3.99 (s, 2H), 4.14 (t, J = 6.6 Hz, 2H), 7.39–7.94 (m, 5H). 13C NMR (CDCl3,
75 MHz): d 13.5, 19.1, 30.7, 46.3, 69.1, 128.2, 128.5, 128.8, 133.6, 167.6, 192.5.;
EI MS (m/z): 236 (M+). Anal. Calcd for C13H16O2S: C, 66.07; H, 6.82; S, 13.57.
Found: C, 66.25; H, 6.73; S, 13.53.
O-Isopropyl 3-oxo-3-phenylpropanethioate (8k): viscous pale yellow liquid, 1H
NMR (CDCl3, 400 MHz): d 1.20 (d, J = 6.6 Hz, 6H), 3.93 (s, 2H), 5.04–5.07 (m,
1H), 7.42–7.57 (m, 3H), 7.91–7.95 (m, 2H);13C NMR (CDCl3, 75 MHz): d 21.6,
46.3, 69.1, 128.3, 128.5, 128.7, 133.6, 167.1, 192.7; EI MS (m/z): 222 (M+). Anal.
Calcd for C12H14O2S: C, 64.83; H, 6.35; S, 14.42. Found: C, 64.73; H, 6.45; S,
14.39.
O-tert-Butyl 3-oxo-3-phenylpropanethioate (8m): viscous pale yellow liquid, 1H
NMR (CDCl3, 400 MHz): d 1.25(s, 9H), 3.95(s, 2H), 7.45–7.58 (m, 3H), 7.91–7.94
(m, 2H); 13C NMR (CDCl3, 75 MHz): 26.1, 46.5, 69.9, 128.5, 128.7, 128.9, 133.7,
167.3, 192.9; EI MS (m/z): 236 (M+). Anal. Calcd for C13H16O2S: C, 66.07; H,
6.82; S, 13.57. Found: C, 66.15; H, 6.75; S, 13.49.