Perchloric acid adsorbed on silica gel (HClO4-SiO2) as an extremely efficient and reusable catalyst for 1,3-dithiolane/dithiane formation

Article abstract of DOI:10.1055/s-2006-942474

Perchloric acid adsorbed on silica gel (HClO₄-SiO₂) has been found to be an extremely efficient and reusable catalyst for 1,3-dithiolane and 1,3-dithiane formation under solvent-free conditions at room temperature. Georg Thieme Verla

Full text of DOI:10.1055/s-2006-942474

PAPER
2767
Perchloric Acid Adsorbed on Silica Gel (HClO -SiO ) as an Extremely
4
2
Efficient and Reusable Catalyst for 1,3-Dithiolane/Dithiane Formation
H
S
ClO -Si O
a
a
a
Catalyst
n
for 1,3-Dith
t
iolane/D
o
ithiane
F
or
s
m
ation h Rudrawar, Ram C. Besra, Asit K. Chakraborti*
4
2
National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Punjab 160062, India
Fax +91(172)2214692; E-mail: akchakraborti@niper.ac.in
Received 28 March 2006; revised 10 April 2006
The tight legislation on the maintenance of ‘green’ syn-
thetic pathways and processes that requires the prevention
of waste formation (e.g. metallic impurities from cata-
lysts), avoiding the use of auxiliary substances (e.g. halo-
genated and high boiling solvents), and minimizing the
energy requirement influenced us to design a new meth-
od, which operated under metal- and solvent-free condi-
tions, at room temperature, in short reaction times to
afford high yields so as to overcome the existing disad-
vantages and fulfill the triple bottom-line philosophy of
green chemistry.18
Abstract: Perchloric acid adsorbed on silica gel (HClO -SiO ) has
been found to be an extremely efficient and reusable catalyst for
4
2
1
,3-dithiolane and 1,3-dithiane formation under solvent-free condi-
tions at room temperature.
Keywords: HClO –SiO , catalyst, dithiolanes, dithianes, solvent-
4
2
17
free
1
,3-Dithiolane and 1,3-dithiane formation are important
organic transformations due to their versatile applications
1
in the protection of carbonyl groups, generation of um-
2
poled carbonyls, conversion of carbonyl groups to meth- The leading contenders for environmentally acceptable
3
19
ylene derivatives, and titanium alkylidene mediated processes are supported reagents. Since the activity and
4
carbonyl olefination. Dithiolane/dithiane containing selectivity of a reagent dispersed on the surface of a sup-
compounds possess a broad spectrum of biological activ- port is improved as the effective surface area of the re-
5
6
ity such as leishmanicidal, anti-HIV, interferon-gamma agent can be increased manifold, the reaction is expected
and lipopolysaccharide-induced nitric oxide production to be complete in short reaction times. Good thermal and
7
8
8,9
inhibitor, anti-convulsant, radioprotective,
anti-tu- mechanical stabilities, ease of handling due to invariably
mor, radical scavenging, and hepatoprotective proper- low toxicity and non-corrosive free flowing nature, ease
1
0
1
1
ties. Other uses are found in the synthesis of new of separation from the reaction mixture through filtration,
antibacterial penem compounds and process stabilizers and scope of reuse make supported reagents suitable for
for polyolefins. Thus, there has been unbound interest in industrial applications. Herein we report that perchloric
,3-dithiolane/dithiane synthesis, which has led to the de- acid adsorbed on silica gel (HClO -SiO ) is an extreme-
1
2
1
3
1
9e
1
4 2
velopment of various methodologies. These include, con- ly efficient and reusable catalyst for 1,3-dithiolane and
densation of a carbonyl compound with 1,2-ethanedithiol/ 1,3-dithiane formation.
1
,3-propanedithiol in the presence of various acid cata-
Various aromatic, heteroaromatic, and alicyclic aldehydes
and ketones upon treatment with 1,2-ethanedithiol (1) and
1
,14
lysts that can be classified as: (i) metal salts/complex,
1
,15
(
ii) solid acids,
and (iii) protic/Lewis acids on solid
1
,3-propanedithiol (2) in the presence of HClO -SiO (1
4 2
1
,16
support (Scheme 1). However, various drawbacks such
as moderate yields, long reaction times, harsh reaction
conditions, tedious work-up, use of expensive reagents,
use of solvents and toxic agents, special efforts required to
prepare the catalyst, requirement for special apparatus,
etc. associated with many of these methods make the de-
velopment of a more efficient catalyst necessary.
mol%) afforded the corresponding dithiolane/dithiane in
5–100% yields after 1–30 min (TLC, IR) under solvent-
7
free conditions at room temperature (Table 1). The reac-
tion was compatible with a wide range of functional
groups such as hydroxyl, alkoxy, halogen, cyano, nitro
etc. that are likely to compete for coordination with the
20
catalyst and for substrates (Table 1, entries 22 and 24)
that are sensitive to acid. Excellent chemoselectivity was
n
observed for a,b-unsaturated substrates (Table 1, entries
O
Catalyst
n
21
+
S
S
R
19 and 20) without any competitive conjugate addition.
R2 R1
SH SH
2
1
R
No aqueous work-up was needed, the products were easi-
ly isolated from the reaction mixture by dilution with
EtOAc followed by filtration, and the catalyst was recov-
ered and reused without significant loss of activity (see
experimental procedure).
Scheme 1 Lewis acid catalyzed formation of 1,3-dithiolane/dithi-
ane from carbonyl compounds and dithiols
The present method is convincingly superior to the report-
ed procedures with respect to reaction time and tempera-
ture, yield, amount of catalyst, and solvent-free conditions
employed. This claim is justified through a few represen-
SYNTHESIS 2006, No. 16, pp 2767–2771
x
x.
x
x
.
2
0
0
6
Advanced online publication: 04.07.2006
DOI: 10.1055/s-2006-942474; Art ID: Z05806SS
Georg Thieme Verlag Stuttgart · New York
©

2
768
S. Rudrawar et al.
PAPER
tative examples in which the efficiency of HClO -SiO2 one minute under solvent-free conditions in the presence
4
has been compared with those of recently reported (i) of HClO -SiO (1 mol%) is superior. The dithiolane for-
4
2
Lewis acid, (ii) solid acid, and (iii) supported Lewis/protic mation of 1-naphthaldehyde demonstrated the superiority
acid catalysts. The 1,3-dithiolane of benzaldehyde was of the present methodology over Cu(BF ) ·xH O which
4
2
2
obtained in 90%, 96%, 78%, 95%, and 89% yields in provided an 86% yield after 30 minutes1 compared to the
4f
MeCN, CH Cl –MeOH, THF, MeCN, and MeCN after 99% yield afforded by the HClO -SiO -catalyzed reac-
2
2
4
2
6
0, 165, 300, 90, and 90 minutes in the presence of LiBF
tion. During the present investigation, Cu(BF ) ·xH O-
4
4 2 2
1
4a
14b
(
10 mol%),
NiCl2 (10 mol%),
Bi(NO3)3 (0.1 catalyzed reaction of 2-acetylfuran and 2-acetylthiophene
1
4c
4e
14d
mol%), MoO (acac) (10 mol%), and Y(OTf) (5 with 1,2-ethanedithiol afforded 71% and 50% yields, re-
mol%), respectively. The dithiolane was formed in 95% spectively, after a reaction time of 30 minutes at room
yield by Amberlyst 15 -catalyzed (10%) transthioacetal- temperature, compared to 83% and 75% yields, respec-
2
2
3
1
®
ization of benzaldehyde with 2,2-dimethyl-1,3-dithiolane tively, obtained after ten minutes in the presence of
1
5
under microwave irradiation at 190 °C for 15 minutes.
HClO -SiO . The reaction of acetophenone with 1,2-
4 2
1
6a
SiO -AlCl (33 mol%) in DCE under reflux afforded a ethanedithiol afforded a 45% yield (GCMS) of the dithi-
2
3
9
5% yield after 72 minutes and a 97% yield was obtained olane after five hours at room temperature, whereas quan-
in CH Cl at room temperature after 30 minutes when the titative formation of dithiolane took place when the
2
2
16b
reaction was catalyzed by PPA-SiO (0.25 g/mmol).
reaction was catalyzed by HClO -SiO .
4 2
2
Compared to these results, the 96% yield obtained after
a
Table 1 HClO –SiO -Catalyzed Dithiolane/Dithiane Formation
4
2
Entry
1
Substrate
Dithiol
Time (min)
1
Yield (%)b,c
96
CHO
R5
1
R1
R2
3
R4
R3
1
2
4
5
R = R = R = R = R = H
1
2
3
4
5
2
3
4
5
6
7
8
9
R = R = R = R = R = H
2
1
1
2
1
1
1
2
1
1
2
1
1
1
1
1
1
1
1
1
99
93
88
98
93
96
99
100
98
80
85
88
98
99
97
96
94
82
1
2
4
5
3
R = R = R = R = H; R = Me
1
2
4
5
3
R = R = R = R = H; R = OMe
3
1
2
4
5
3
R = R = R = R = H; R = OMe
1
1
3
5
2
4
R = R = R = OMe; R = R = H
1
1
2
4
5
3
R = R = R = R = H; R = OH
1
1
2
4
5
3
R = R = R = R = H; R = Cl
1
1
2
4
5
3
R = R = R = R = H; R = Cl
1
1
2
4
5
3
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
R = R = R = R = H; R = F
1
1
2
4
5
3
R = R = R = R = H; R = NO
10
5
2
2
1
2
4
5
3
R = R = R = R = H; R = NO
1
2
4
5
3
R = R = R = R = H; R = CN
10
2
1
2
4
5
3
R = R = R = R = H; R = CF
3
1
2
4
5
3
R = R = R = R = H; R = OBn
5
1
5
2
4
3
R = R = H; R = R = OMe; R = OH
1
1
2
3
4
5
R = R = OMe; R = R = R = H
3
1
4
5
2
3
R = R = R = H; R = OEt; R = OH
1
CHO
R
10
R = Me
Synthesis 2006, No. 16, 2767–2771 © Thieme Stuttgart · New York

PAPER
HClO -SiO as a Catalyst for 1,3-Dithiolane/Dithiane Formation
2769
4
2
a
Table 1 HClO –SiO -Catalyzed Dithiolane/Dithiane Formation
4
2
Entry
Substrate
R = Ph
Dithiol
Time (min)
Yield (%)b,c
2
2
0
1
1
1
3
5
98
90
CHO
X
X = S
X = O
2
2
2
3
1
1
5
97
83
10
X
O
X = S
X = O
2
2
4
5
1
1
10
10
75
83
CHO
2
6
O
1
5
94
n
n = 1
n = 2
2
2
2
3
7
8
9
0
1
2
1
1
5
1
3
3
96
95
97
99
n = 2
n = 3
CHO
R
R = H
3
3
3
1
2
3
R = OMe
1
2
1
5
1
1
95
93
85
R = OMe
R
n CHO
R = Me; n = 1
R = Ph; n = 1
3
3
3
4
5
6
1
1
1
1
2
94
95
95
R = Ph; n = 2
O
30
R
R = H
3
3
7
8
R = OMe
1
1
25
85
O
5 h
100
a
The carbonyl compound (2.5 mmol) was treated with dithiol (1.2 equiv) in the presence of HClO –SiO (1 mol% in HClO ) at r.t. (ca. 25–
4
2
4
3
0 °C) under solvent-free conditions.
Yield of the corresponding isolated and purified dithiolane/dithiane.
All compounds were characterized by IR, NMR, and mass spectroscopy.
b
c
In conclusion, HClO -SiO is an extremely efficient and lease of waste and use of toxic substance, as a measure to
4
2
1
7
reusable catalyst for 1,3-dithiolane/dithiane formation. control environmental pollution, the solvent free condi-
The advantages are high chemoselectivity, high yields, tions employed in the present method make it ‘environ-
extremely fast reaction, low cost, and operation at room mentally friendly’ and a practical approach for the
temperature. With increasingly tight legislation on the re- synthesis of 1,3-dithiolanes/dithianes.22
Synthesis 2006, No. 16, 2767–2771 © Thieme Stuttgart · New York

2
770
S. Rudrawar et al.
PAPER
Perchloric acid (HClO ) aqueous solution (70%) was purchased
MS (APCI): m/z = 203 (M + 1)+.
Anal. Calcd for C H OS : C, 47.48; H, 4.98. Found: C, 47.50; H,
4
from Loba Chemie, India and silica gel (230–400 mesh) from Spec-
trochem Pvt. Ltd. India. All commercial reagents and solvents were
used without further purification unless otherwise specified. The
8
10
3
4
.97.
1
9e
HClO -SiO was prepared as reported in the literature. NMR
4
2
2
-(2-Methoxy-1-naphthyl)-1,3-dithiolane
spectra were recorded on a Bruker Avance DPX 300 MHz NMR
spectrometer using TMS as an internal standard. Mass spectra were
obtained using a GCMS-QP 5000 (Schimadzu) [for EI] and LCMS-
Finnigan MAT LCQ [for APCI] mass spectrometers. The IR spectra
were recorder on a Nicolet Impact 410 FTIR spectrometer. Elemen-
tal analysis was carried out on an Elementar Vario EL.
White solid; mp 122–124 °C.
IR (KBr): 3014, 2971, 2932, 2840, 1595, 1502, 1441, 1291, 1248,
–
1
1
176, 1149, 1074, 1049, 1025, 798, 744, 582, 539 cm .
1
H NMR (300 MHz, CDCl ): d = 3.42–3.50 (m, 2 H), 3.61–3.70 (m,
3
2
H), 3.94 (s, 3 H), 6.94 (s, 1 H), 7.19 (d, J = 9.1 Hz, 1 H), 7.31–7.36
(
7
dd, J = 7.5, 7.2 Hz, 1 H), 7.46–7.51 (dd, J = 8.0, 7.3 Hz, 1 H),
.73–7.79 (dd, J = 8.9, 7.9 Hz, 2 H), 8.79 (d, J = 8.6 Hz, 1 H).
The spectral data (IR, NMR, and MS) of all known compounds pre-
pared were in full agreement with authentic samples.
1
3
C NMR (75 MHz, CDCl ): d = 40.22, 47.52, 56.95, 113.20,
3
Dithiolane/Dithiane Formation from Carbonyl Compounds;
Typical Procedure
To a magnetically stirred mixture of 4-chlorobenzaldehyde (0.35 g,
1
15.74, 123.62, 125.45, 128.59, 129.73, 130.86, 132.34, 155.65.
MS (ESI): m/z = 262 (M+).
2
.5 mmol) and 1,2-ethanedithiol (0.28 g, 3 mmol) was added
Anal. Calcd for C14
5.37.
H14OS : C, 64.08; H, 5.38. Found: C, 64.10; H,
2
HClO -SiO (50 mg, 0.025 mmol of HClO , 1 mol%) and the mix-
4
2
4
ture was stirred at r.t. under a nitrogen atmosphere for 1 min (TLC).
The reaction mixture was diluted with EtOAc (10 mL) and filtered
through a cotton plug. The residue was washed with EtOAc (2 × 5
mL) and the combined filtrates were concentrated under vacuum to
afford the product (530 mg, 99%).
2-(5-Methoxyindan-1-yl)-1,3-dithiolane
White solid; mp 46–48 °C.
IR (KBr): 2965, 2941, 2339, 1604, 1488, 1466, 1423, 1301, 1263,
–1
1
170, 1139, 1082, 1023, 924, 911, 840, 822, 764, 675 cm .
IR (KBr): 3446, 2903, 1904, 1671, 1589, 1486, 1403, 1277, 1168,
1
H NMR (300 MHz; CDCl ): d = 2.66–2.71 (m, 2 H), 2.90–2.95 (m,
3
–
1
1
084, 1012, 971, 750, 724, 688, 511 cm .
2
H), 3.38–3.52 (m, 4 H), 3.77 (s, 3 H), 6.71 (s, 1 H), 6.77–6.80 (dd,
1
H NMR (300 MHz, CDCl ): d = 3.31–3.40 (m, 2 H), 3.44–3.52 (m,
J = 2.1, 8.4 Hz, 1 H), 7.45 (d, J = 8.4 Hz, 1 H).
13
3
2
H), 5.59 (s, 1 H), 7.25–7.28 (d, J = 8.8 Hz, 2 H), 7.44–7.46 (d,
C NMR (75 MHz, CDCl ): d = 31.50, 41.35, 49.03, 56.00, 73.26,
3
J = 8.2 Hz).
1
09.84, 114.18, 125.95, 137.47, 144.58, 160.59.
1
3
C NMR (75 MHz, CDCl ): d = 40.27, 55.47, 128.59, 129.31,
MS (APCI): m/z = 239 (M + 1)+.
3
1
33.66, 139.04.
Anal. Calcd for C H OS : C, 60.46; H, 5.92. Found: C, 60.44; H,
5
1
2
14
2
+
MS (ESI): m/z = 216 (M ); identical with an authentic sample.
.93.
Catalyst Recovery
The cotton plug was dipped into EtOAc (10 mL) in a 25 mL beaker
to allow the catalyst to settle. The cotton was removed and the
EtOAc decanted off. The recovered catalyst was dried under vacu-
um (5 mmHg) at 100 °C for 2 h and used for two further reactions
with 4-chlorobenzaldehyde (2.5 mmol) to afford the desired product
in 95% and 90% yields.
Acknowledgment
The authors thank the Department of Science and Technology, New
Delhi, India for financial support (Grant No. 93143).
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2
-(2-Methyl[1,3]dithiolan-2-yl)furan
(
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1
154, 1072, 1009, 922, 739 cm .
(
1
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1
6
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1
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8
10
2
5
.42.
(
2
-Methyl-2-thiophen-2-yl[1,3]dithiolane
(
Colorless liquid.
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–1
1
073, 852 cm .
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3
(
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(
1
3
C NMR (75 MHz, CDCl ): d = 34.68, 41.57, 64.95, 125.42,
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3
1
25.83, 127.32, 154.16.
Synthesis 2006, No. 16, 2767–2771 © Thieme Stuttgart · New York

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HClO -SiO as a Catalyst for 1,3-Dithiolane/Dithiane Formation
2771
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2
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2004, 2307.
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Synthesis 2006, No. 16, 2767–2771 © Thieme Stuttgart · New York