Indium(III) chloride catalyzed efficient conversion of carbonyl compounds to 1,3-dithioacetals

Article abstract of DOI:10.1081/SCC-120002509

Several aldehydes and ketones were efficiently converted into their corresponding dithioacetals and 1,3-dithianes in high yields using catalytic amount of indium(III) chloride in dichloromethane.

Full text of DOI:10.1081/SCC-120002509

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INDIUM(III) CHLORIDE CATALYZED EFFICIENT
CONVERSION OF CARBONYL COMPOUNDS TO 1,3-
DITHIOACETALS
J. S. Yadav a , B. V. Subba Reddy a & Sushil Kumar Pandey a
a Organic Chemistry Division-1 , Indian Institute of Chemical Technology , Hyderabad,
500 007, India
Published online: 16 Aug 2006.
To cite this article: J. S. Yadav , B. V. Subba Reddy & Sushil Kumar Pandey (2002) INDIUM(III) CHLORIDE CATALYZED
EFFICIENT CONVERSION OF CARBONYL COMPOUNDS TO 1,3-DITHIOACETALS, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 32:5, 715-719, DOI: 10.1081/SCC-120002509
To link to this article: http://dx.doi.org/10.1081/SCC-120002509
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SYNTHETIC COMMUNICATIONS, 32(5), 715–719 (2002)
INDIUM(III) CHLORIDE CATALYZED
EFFICIENT CONVERSION OF CARBONYL
COMPOUNDS TO 1,3-DITHIOACETALS
J. S. Yadav,* B. V. Subba Reddy, and
Sushil Kumar Pandey
Organic Chemistry Division-1, Indian Institute of
Chemical Technology, Hyderabad-500 007, India
ABSTRACT
Several aldehydes and ketones were efficiently converted
into their corresponding dithioacetals and 1,3-dithianes in
high yields using catalytic amount of indium(III) chloride in
dichloromethane.
Acetals and thioacetals are the most commonly used protecting groups
for aldehydes and ketones in multi-step synthesis of many natural products.
Among various acetals, dithioacetals and 1,3-dithianes are versatile because
of their use as nucleophilic acylating agents in carbon–carbon bond forming
reactions.
As a result, several methods have been reported for the preparation of
thioacetals from aldehydes and thiols using protic as well as Lewis acids as
catalysts. In addition lithium salts have also been used for this transforma-
tion. However, many of these procedures are often accompanied by the use
of stoichiometric amount of catalysts, moisture sensitive reagents, longer
*Corresponding author.
715
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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YADAV, SUBBA REDDY, AND KUMAR PANDEY
reaction times and low yields of products in case of aliphatic aldehydes.
Even though, zinc triflate and trialkylsilyl triflates are found to be effective,
there are still some limitations regarding selectivity and incompatibility
with other functional groups. In recent years, InCl3 has received consider-
able attention as a mild Lewis acid in various transformations such as
Mukaiyama aldol reactions, Diels-Alder reactions, Mannich reactions,
Prins type cyclizations and Michael reactions in both aqueous and non-
aqueous medium. Unlike traditional Lewis acids, InCl3 is stable and reco-
verable in water. These unique properties inherent to InCl3 prompted us to
explore this catalyst for dithioacetalization of carbonyl compounds.
In this report, we wish to introduce InCl3 as a new and efficient
catalyst for thioacetalization of aldehydes and ketones with thiols under
mild conditions. The reaction of benzaldehyde with ethane 1,2-dithiol in
the presence of 10 mol% InCl3 in dichloromethane gave 1,3-dithiane deri-
vative in 90% yield. Similarly, several aromatic, aliphatic, a,b-unsaturated
and heterocyclic aldehydes were efficiently converted into the corresponding
dithioacetals in the presence of indium(III) chloride. However, aliphatic and
aromatic ketones took longer reaction times to achieve comparable yields
with those of their aldehyde analogues. The reactions proceeded smoothly at
ambient temperature to afford dithioacetals in high yields.
The cyclic ketones like cyclohexanone, cyclopentanone, tetralone and
4-phenyl cyclohexanone reacted with dithiol and monothiol to give the
corresponding dithioacetals in high yields. Acid sensitive substrate like
furfural is also protected as dithioacetal in good yield without the formation
of any side products. Acyclic ketones like benzophenone, acetophenone,
3-pentanone, and 2-hexanone were also converted into dithioacetals in
good yields. The tolerance of various functional groups under the present
reaction conditions have been examined by reacting the substrates bearing
OBn, OPh, OMe, methylenedioxy, cyano, olefinic groups and the reaction
conditions are compatible with these functional groups. When ethane
1,2-dithiol was replaced with propane 1,3-dithiol gave the corresponding
1,3-dithiane derivatives in good yields.

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DITHIOACETALS AND 1,3-DITHIANES
717
In conclusion, InCl3 is found to be an highly efficient and recoverable
catalyst for the conversion of carbonyl compounds into dithioacetals under
mild reaction conditions. The procedure offers several advantages including
mild reaction conditions, high yields of products, catalytic amount of the
reagent, regeneration of the catalyst, cleaner reactions, simple experimental
and product isolation procedure which makes it a useful and attractive
procedure for this transformation.
EXPERIMENTAL
General procedure: A mixture of carbonyl compound (5 mmol) dithiol
(5 mmol) or monothiol (10 mmol) and InCl3 (0.5 mmol) in dichloromethane
(15 ml) was stirred at room temperature for an appropriate time (table).
After completion of the reaction as indicated by TLC, the reaction mixture
Table. InCl3 Catalyzed Formation of Dithioacetals and 1,3-Dithianesa
Reaction
Time (h)
Yieldb
(%)
Entry
Carbonyl Compound
Thiol
a
b
c
d
e
f
g
h
i
C6H5CHO
HSCH2CH2SH
CH3CH2SH
HSCH2CH2SH
HSCH2CH2SH
CH3CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2CH2SH
HSCH2CH2SH
CH3CH2SH
2.5
2.0
3.5
2.5
3.0
6.0
3.5
4.0
5.0
2.5
2.0
90
88
81
87
75
70
85
89
80
90
92
4-MeC6H4CHO
3,4-Cl2C6H3CHO
3,4-(EtO)2C6H3CHO
3-PhOC6H4CHO
3-NO2C6H4CHO
PhCH¼CHCHO
Piperonal
1-Naphthaldehyde
2-Furfuraldehyde
Thiophene-
j
k
HSCH2CH2SH
2-carboxaldehyde
3-Phenylpropanal
n-Hexanal
Cyclohexanone
3-Pentanone
2-Hexanone
Tetralone
Acetophenone
4-Phenylcyclohexanone
l
HSCH2CH2SH
HSCH2CH2CH2SH
CH3CH2SH
3.5
4.0
5.0
6.5
7.0
4.5
5.5
5.0
83
85
80
75
70
82
85
80
m
n
o
p
q
r
CH3CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2SH
HSCH2CH2CH2SH
s
1
aAll products were characterized by H NMR, IR and mass spectra.
bIsolated yields after purification.

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YADAV, SUBBA REDDY, AND KUMAR PANDEY
was diluted with water (10 ml) and extracted twice with dichloromethane
(2 Â 10 ml). The combined organic layers were dried over anhydrous
Na2SO4, concentrated in vacuo and purified by column chromatography
on silica gel (Merck, 100–200 mesh, ethyl acetate–hexane, 1 : 9) to give
pure dithioacetal.
Representative spectroscopic data for compounds: a: 1H NMR
(200 MHz; CDCl3): d 3.50 (s, 4H); 5.75 (s, 1H); 7.25–7.40 (m, 5H). EIMS:
m/z: 182 Mþ, 165, 154, 136, 122, 91, 77. IR (KBr) n: 2965, 2855, 1446, 1374,
1
1246, 1189, 1130, 1050, 976, 822. b: H NMR (200 MHz; CDCl3): d 1.25
(t, 6H, J ¼ 6.8 Hz); 2.35 (s, 3H); 2.55 (m, 4H); 4.90 (s, 1H); 7.15 (d,
2H, J ¼ 7.8 Hz); 7.35 (d, 2H, J ¼ 7.8 Hz). EIMS: m/z: 226 Mþ, 165, 136,
104, 91, 69, 55, 43. IR (KBr) n: 2968, 2870, 1510, 1375, 1264, 1183, 1153,
1110, 1049, 974, 830. m: 1H NMR (200 MHz; CDCl3): d 1.05 (t, 3H,
J ¼ 7.0 Hz); 1.15 (m, 8H); 2.70 (m, 2H); 4.50 (m, 4H); 4.60 (t, 1H,
J ¼ 7.0 Hz). FAB Mass: m/z: 190 Mþ, 119, 73. IR (KBr) n: 2929, 1588,
1
1424, 1379, 1271, 1180, 907, 730. n: H NMR (200 MHz; CDCl3): d 1.15
(t, 6H, J ¼ 6.8 Hz); 1.45 (m, 2H); 1.65 (m, 4H); 1.85 (t, 4H, J ¼ 6.8 Hz); 2.60
(q, 4H, J ¼ 6.8 Hz). EIMS: m/z: 204 Mþ, 175, 143, 81, 75, 43. IR (KBr)
n: 2965, 2855, 1446, 1374, 1264, 1189, 1130, 1050, 1008, 976, 883, 822.
o: 1H NMR (200 MHz; CDCl3): d 0.95 (t, 6H, J ¼ 6.8 Hz); 1.20 (t, 6H,
J ¼ 6.8 Hz); 1.65 (q, 4H, J ¼ 6.8 Hz); 2.60 (q, 4H, J ¼ 6.8 Hz). EIMS:
m/z: 192 Mþ, 163, 131, 102, 69, 55, 43. IR (KBr) n: 2969, 2872, 1455,
1375, 1322, 1260, 1160, 1132, 1069, 1048, 976, 922, 863. r: 1H NMR
(200 MHz; CDCl3): d 2.15 (s, 3H); 3.35 (s, 4H); 7.35–7.45 (m, 5H). FAB
Mass: m/z: 196 Mþ, 181, 136, 121, 103, 91, 77. IR (KBr) n: 2924, 1440, 1274,
1059, 845, 765, 699.
ACKNOWLEDGMENTS
BVS thanks CSIR, New Delhi and SKP thanks IICT for the award of
fellowships.
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Received in the UK December 8, 2000

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