A rapid and efficient method for 1,3-dithiolane synthesis

Article abstract of DOI:10.1016/j.tetlet.2006.05.057

A mild, efficient and solvent-free protocol for conversion of aldehydes and ketones into their corresponding 1,3-dithiolanes using 1,2-ethanedithiol in the presence of a catalytic amount of SnCl₂·2H₂O is reported.

Full text of DOI:10.1016/j.tetlet.2006.05.057

Tetrahedron Letters 47 (2006) 5155–5157
A rapid and efficient method for 1,3-dithiolane synthesis
*
Ghanashyam Bez and Dipankoj Gogoi
Department of Chemistry, Dibrugarh University, Dibrugarh 786004, Assam, India
Received 25 February 2006; revised 5 May 2006; accepted 11 May 2006
Available online 6 June 2006
Abstract—A mild, efficient and solvent-free protocol for conversion of aldehydes and ketones into their corresponding 1,3-dithiol-
anes using 1,2-ethanedithiol in the presence of a catalytic amount of SnCl Æ2H O is reported.
2 2
Ó 2006 Elsevier Ltd. All rights reserved.
Protection and deprotection of reactive functional
groups in organic compounds is very important in
multistep organic synthesis. Besides choosing the right
protecting group with optimum stability, the selection
of a mild and efficient catalyst to affect these protection
and deprotection processes also play a pivotal role in
dictating the efficiency.
We set out to explore the possibility of using a catalytic
amount of SnCl Æ2H O, an extremely mild Lewis acid
2
2
1
for protection of aldehydes and ketones as 1,3-dithiol-
anes, by reaction with 1,2-ethanedithiol. To establish
the catalytic activity, SnCl Æ2H O (0.05 mmol) was
2
2
ground with p-methylbenzaldehyde (1 mmol) and then
stirred with 2 equiv of 1,2-ethanedithiol at room temper-
ature. Monitoring the progress of the reaction by TLC,
we found that the reaction did indeed take place under
these conditions and the rate of conversion was very
good (75% yield, after 2.5 h). The use of 1 mL of diethyl
ether in the reaction mixture resulted in complete con-
version within 45 min. Next, the rate of conversion for
the same reaction was studied in various solvents (Table
1, entry 1), at rt and at reflux temperature ultimately.
Diethyl ether was the best solvent affecting this conver-
sion within 11 min. However, the fact that the reaction
took place under solvent-free conditions prompted us
to investigate the effect of microwave (MW) irradiation.
When p-methylbenzaldehyde and 1,2-ethanedithiol were
irradiated with microwaves at 100 W in the presence of
5 mol % SnCl Æ2H O, the reaction went to completion
1
Protection of carbonyl compounds as 1,3-dithiolanes is
an important protocol in organic synthesis because of
their easy introduction, stability towards acidic media
and a wide range of homogeneous and heterogeneous
2
reagents are available to deprotect thioacetals. Thioace-
tals and oxathioacetals find applications as important
starting materials for stereoselective synthesis, where
they can act as acyl anion equivalents in carbon–carbon
3
bond forming reactions. The protection of carbonyls as
4
1
,3-dithiolanes can be accomplished using BF ÆEt O,
3 2
8
5
6
7
InCl3, TiCl , Sc(OTf) , Mg and Zn triflates, and
4
3
9
Ni(BO3)3 in homogeneous reaction conditions, silica
1
0
11
12
gel treated with SOCl , Amberlyst-15, zeolites,
2
1
3
3+
14
Nafion-H, Fe -montmorillonite, CoBr2 on silica
2
2
1
5
16
17
18
gel, ZrCl4, Envirocat EPZG, Cu(OTf) -silica gel
and heteropoly acids
conditions.
within three minutes giving the corresponding protected
2
1
9
22
in heterogeneous reaction
aldehyde in 89% yield. The reaction was then general-
ised as shown in Table 1 (Scheme 1).
Organic reactions under solvent-free conditions20 have
become increasingly popular because of their opera-
tional simplicity. Moreover, recent years have witnessed
a phenomenal growth in the application of microwave
The substrate catalyst ratio was then optimised (Table
2). An increase of reaction time from 3 to 5 min did
not change the yield considerably, when 2 mol % cata-
lyst was used (Table 2, entry 1). Increase in the catalyst
ratio from 5 to 7 mol % and 10 mol % did not change
the yield and the reactions (Table 2, entries 3–5) went
to completion in only 3 min. Therefore, 5 mol %
SnCl Æ2H O was the optimum catalyst ratio for this
(
MW) irradiation21 in organic transformations.
*
Corresponding author. Tel.: +91 373 2370210/094353 31739; fax:
91 373 2370323; e-mail: ghanashyambez@yahoo.com
2
2
+
conversion.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.057

5156
G. Bez, D. Gogoi / Tetrahedron Letters 47 (2006) 5155–5157
a
2 2
Table 1. SnCl Æ2H O catalysed formation of 1,3-dithiolanes via Scheme 1
b
c
Entry
1
Substrate
p-CH
Conditions
Time (min)
Yield (%)
3
C
6
H
4
CHO
Solvent free, rt
Diethyl ether, rt
Diethyl ether, reflux
Methylene chloride, reflux
Chloroform, reflux
150
45
11
75
30
25
145
3
3
3
3
4
3
5
3
4
4
5
4
4
75
80
90
75
83
85
80
89
92
75
86
81
82
Tetrahydrofuran, reflux
Acetonitrile, reflux
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
Solvent free, lW, 180 W
Solvent free, lW, 100 W
Solvent free, lW, 100 W
2
3
4
5
6
7
8
9
p-ClC
CHO
p-NO
p-OH C
6
H
4
CHO
C
6
H
5
2
C
6
H
4
CHO
CHO
CHO
6
H
4
p-OMeC
6
H
4
d
Citral
68
n-Octanal
m-(CO Me)C
86
91
90
89
93
92
85
75
75
96
83
84
2
6
H
4
CHO
10
11
12
13
14
15
16
17
18
19
p-Bromo acetophenone
Acetophenone
Cyclohexanone
Cyclopentanone
Menthone
4
3
15
12
4
Carvone
Benzophenone
Benzophenone
Methyl acetoacetate
Cholestanone
5
O
O
2
0
1
O
Solvent free, lW, 100 W
Solvent free, lW, 100 W
30
5
No reaction
81
O
O
O
2
Vanillin
a
b
c
2 2
Substrate–1,2-ethanedithiol–SnCl Æ2H O = 1:1:0.05.
Microwave irradiation using a Samsung microwave oven, Model-1630N.
Yield of the isolated pure product which was characterised by H NMR, IR and mass spectroscopy.
Another unidentified by-product was observed.
1
d
R1
HS
HS
R1
S
S
unidentified by-products was formed besides the desired
product. Interestingly, citral (entry 7) gave a 68% yield
as against a 55% yield (13% increase in % of yield) when
the amount of 1,2-ethanedithiol was reduced to 1 equiv
from 2 equiv. Both cyclic and acyclic ketones (Table 1,
entries 10–19) gave very good yields of the desired 1,3-
dithiolanes. Even benzophenone (entry 16) also gave
SnCl ·2H O (5 mol%), μW
2
2
O +
R2
solvent-free
R2
Scheme 1.
7
5% of its 1,3-dithiolane derivative when treated with
Table 2. Optimisation of the amount of SnCl
of 1,3-dithiolanes of p-methylbenzaldehyde
2
Æ2H
2
O in the formation
1 equiv of 1,2-ethanedithiol for 15 min. Changing the
power to 180 W (entry 17) gave an even better result.
The reaction went to completion within 12 min giving
a 96% yield. Shi’s Ketone (entry 20) was recovered intact
even after microwave irradiation for 30 min.
a
b
Entry
Substrate
Mol %
catalyst
Time
(min)
Yield
(%)
1
2
3
4
5
2
2
5
7
10
3
5
3
3
3
52
55
89
88
89
In order to study the chemoselectivity of our method, 3-
oxo-butyraldehyde was treated with 1,2-ethanedithiol
(1 equiv). The aldehyde group was protected as its 1,3-
3 6 4
p-CH C H CHO
a
Microwave irradiation using a Samsung microwave oven, Model-
630N.
Yield of the purified product.
1
b
O
HS
HS
O
S
SnCl ·2H O (5 mol%)
2
2
(1 equiv)
CHO +
μW
S
Both aliphatic and aromatic aldehydes (Table 1, entries
–9 and 21) gave reasonably good yields of 1,3-dithiol-
anes, except citral (Table 1, entry 7), in which case, an
1
Scheme 2.

G. Bez, D. Gogoi / Tetrahedron Letters 47 (2006) 5155–5157
5157
dithiolane in preference to the ketone functionality
Scheme 2).
8. Corey, E. J.; Shimoji, K. Tetrahedron Lett. 1983, 24, 169–
72.
1
(
9
. Srivastava, N.; Dasgupta, S.; Banik, B. K. Tetrahedron
Lett. 2003, 44, 1191–1193.
In conclusion, we have reported an efficient and chemo-
selective and yet simple, straightforward, environmen-
tally benign protocol for the synthesis of 1,3-
dithiolanes from carbonyl compounds using SnCl2Æ
1
0. Kamitori, Y.; Hojo, M.; Masuda, R.; Kimura, T.;
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1
1
2
H O. No aqueous work-up, no solvent, dehydrating
2
agent, anhydrous atmosphere or tedious removal of
water during the reaction were required. The compati-
bility of the catalyst with acid sensitive functional
groups such as nitro, methoxy, carbomethoxy, 1,3-
dioxolane, etc. were the main advantages of the method.
13. Olah, G. A.; Narang, S.; Meider, D.; Salem, G. F.
Synthesis 1981, 282–283.
1
4. Chaudhury, B. M.; Sudha, Y. Synth. Commun. 1996, 26,
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7
1
1
5. Patney, H. K. Tetrahedron Lett. 1994, 35, 5717–5718.
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Acknowledgements
4
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1
1
The authors are grateful to the Vice-Chancellor, Dibru-
garh University for providing the facilities for our work.
Help from Dr. Nabin C. Barua, Sc F and Deputy Direc-
tor, RRL, Jorhat, India is gratefully acknowledged.
1
4
5
2
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References and notes
1
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22. Typical procedure: A mixture of p-methylbenzaldehyde
(0.240 g, 2 mmol), 1,2-ethanedithiol (0.188 g, 2 mmol) and
SnCl Æ2H O (0.023 g, 0.1 mmol) was taken in an Erlen-
2
. Kocienski, P. J. Protecting Groups, 3rd ed.; Thieme:
Stuttgart, 2003.
2
2
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. (a) Utimoto, K.; Nakamura, A.; Matsubara, S. J. Am.
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Lynch, J. E.; Eliel, E. L. J. Am. Chem. Soc. 1984, 106,
meyer flask and irradiated with microwaves. After a few
seconds, the SnCl Æ2H O dissolved in the reaction mixture.
2
2
By monitoring with TLC, the conversion was found to be
complete in 3 min. After cooling, the homogeneous
mixture was passed through a small silica gel (60–120
mesh) pad and the product was eluted using 1% ethyl
acetate in hexane as eluent. Yield = 89% (0.349 g,
1.78 mmol). IR (KBr): 740, 820, 840, 1025, 1080, 1290,
2
943–2948.
4
5
6
7
. Hatch, R. P.; Shringerpure, J.; Weinreb, S. M. J. Org.
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347–1350.
À1
1
1400, 1480, 2870 cm ; H NMR (300 MHz, CDCl ): d
3
2.35 (s, 3H), 3.25–3.45 (m, 4H), 5.55 (s, 1H), 7.09 (d, 2H),
1
3
2
7.40 (d, 2H) ppm; C NMR (75 MHz, CDCl ): 21.01,
3
40.08, 56.05, 127.75, 129.10, 137.07, 137.75 ppm; MS: m/z
196, 168, 153, 135, 91, 45.
1