Chemoselective thioacetalization and transthioacetalization of carbonyl compounds catalyzed by immobilized scandium(III) triflate in ionic liquids

Article abstract of DOI:10.1016/S0040-4039(03)00580-X

Immobilized scandium triflate [Sc(OTf)₃] in ionic liquids has been found to be an extremely efficient and recyclable catalyst for the thioacetalization and transthioacetalization of both aromatic and aliphatic aldehydes. Significant rate acceleration and chemoselectivity was achieved by employing this catalytic system.

Full text of DOI:10.1016/S0040-4039(03)00580-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3337–3340
Chemoselective thioacetalization and transthioacetalization of
carbonyl compounds catalyzed by immobilized scandium(III)
triflate in ionic liquids
Ahmed Kamal* and Gagan Chouhan
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received 13 January 2003; revised 19 February 2003; accepted 28 February 2003
Abstract—Immobilized scandium triflate [Sc(OTf) ] in ionic liquids has been found to be an extremely efficient and recyclable
3
catalyst for the thioacetalization and transthioacetalization of both aromatic and aliphatic aldehydes. Significant rate acceleration
and chemoselectivity was achieved by employing this catalytic system. © 2003 Elsevier Science Ltd. All rights reserved.
Thioacetalization and transthioacetalization are well
studied processes for the conversion of carbonyl com-
pounds and their O,O-acetals to the corresponding
thioacetals. Thioacetals are important protecting
groups for the total synthesis of complex natural prod-
ucts because of their enhanced stability under acidic
ture and pressure. A further limitation is the use of the
highly volatile solvent, dichloromethane, in this
reaction.
Recently, there have been a considerable number of
reports regarding ionic liquids and their use for immo-
bilizing catalysts thereby improving the stability of and
1
conditions compared to O,O-acetals. Transthioacetal-
ization of acetals is a useful transformation for the
12
facilitating the recovery of the catalyst. In this pro-
2
preparation of S,S-acetals and, in comparison to
cess, a catalyst having a polar or ionic character can be
immobilized without structural modification and the
ionic solution containing the catalyst can be separated
from reagents and products.
thioacetalization of carbonyl compounds, is a rapid and
cleaner reaction process. In general thioacetals are pre-
pared by protic or Lewis acid catalyzed condensation of
carbonyl compounds and their O,O-acetals with thi-
3
–10
ols.
However, there are some disadvantages of these
Scandium triflate immobilized in ionic liquids has been
methods, e.g. long reaction times; reflux temperatures;
poor selectivity when applied to mixtures of aldehydes
and ketones; and the catalyst cannot be recovered and
reused.
13
14
used for Friedel–Crafts and Diels–Alder reactions.
Herein, we wish to report thioacetalization and
transthioacetalization of carbonyl compounds and their
O,O-acetals using an efficient and recyclable catalytic
system, Sc(OTf) immobilized in air and moisture stable
ionic liquids.
In a previous report, we demonstrated that scandium
triflate is an efficient and recyclable catalyst for thio-
acetalization. However, disadvantages of this process
are difficulties in recovering the catalyst quantitatively
after each run and drying the catalyst at high tempera-
3
1
1
+
The ionic liquids [bmim][X] 1a–b ([bmim] =1-butyl-3-
methylimidazolium cation; 1a: X=PF ; 1b: X=BF )
6
4
*
0
Corresponding author. Tel.: +91-40-7173874x2638; fax: 91-40-7173757; e-mail: ahmedkamal@iict.ap.nic.in
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00580-X

3
338
A. Kamal, G. Chouhan / Tetrahedron Letters 44 (2003) 3337–3340
+
and [hmim][PF6] ([hmim] =1-hexyl-3-methylimida-
zolium cation) were prepared by stirring a mixture of
N-methylimidazole with 1.2 equiv. of n-butyl or n-
hexyl chloride at 78°C for 30 h under nitrogen followed
by the metathesis reaction of these imidazolium halides
with 1.3 equiv. of HPF in water and NaBF in acetone
6 4
Table 1. Thioacetalization and transthioacetalization of carbonyl compounds using Sc(OTf) immobilized in ionic liquid 1a
3

A. Kamal, G. Chouhan / Tetrahedron Letters 44 (2003) 3337–3340
3339
Scheme 1.
for 2 days. Purification of these ionic liquids was car-
ried out as described in the literature.
of the catalyst is required (Table 1, products 4b, 4f, 4i,
1
5
11
4j).
Initially, benzaldehyde (1 mmol) and scandium triflate
2 mol%) in [bmim][PF ] 1a (1 ml) was treated with 2.2
Moreover, this procedure is highly chemoselective,
providing selective protection of an aldehyde in the
presence of a ketone, c.f. the use of mixtures of the
aldehydes (3e and 3g) and ketones (5a and 5b) as shown
in Scheme 1.
(
6
equiv. of ethanethiol to furnish the corresponding
thioacetal in 95% yield in 9 min. A wide range of
aldehydes and acetals derived from aromatic, and
aliphatic aldehydes also formed thioacetals with
16
The catalytic activity of the ionic liquid [bmim][PF ]
ethanethiol in short reaction times and high yields.
6
17
(
1a) has also been investigated for this type of reac-
tion in the absence of Sc(OTf)3 but no reaction
occurred even after a prolonged reaction time (Scheme
The generality of the process was investigated with a
wide range of aromatic, aliphatic and heterocyclic alde-
hydes and the results are illustrated in Table 1.
2
).
In conclusion, we have demonstrated that ionic liquids
act as a versatile media not only for efficient catalyst
recycling but also for enhancing the rate of the reaction
and improving selectivity in scandium(III) triflate cata-
lyzed thioacetalization. In the present process the
immobilized catalytic system has been reused three
times without any change in catalytic activity. Hence
this new technique involving the application of an ionic
liquid could have potential to address intrinsic prob-
lems (low catalytic activity, selectivity and the structure
modification of the catalyst) of homogenous catalysis.
Moreover, in this reaction the ionic liquid was used in
stoichiometric amounts, which addresses a problem of
environmental and economical sustainability.
The activity of several ionic liquids (1a–b and 2) was
evaluated for thioacetalization with similar behavior
being observed. Sc(OTf) is partially soluble in ionic
3
liquids and exists as a suspension in [bmim][PF ] (1a)
6
and [hmim][PF ] (2), whereas in the hydrophilic ionic
6
liquid [bmim][BF ] (1b), it is highly soluble and is
4
totally immobilized. The products were obtained in
excellent yields using these ionic liquids. Moreover, the
ionic liquid phase containing Sc(OTf) was effectively
3
quantitatively recovered and reused three times by sim-
ple extraction of the product with Et O (Table 1, see
2
entry a).
It is interesting to note that reaction rates and yields for
the thioacetalization process in ionic media are faster
and much improved in comparison to those reported in
non-ionic media, i.e. in dichloromethane where 4 mol%
Scheme 2.

3
340
A. Kamal, G. Chouhan / Tetrahedron Letters 44 (2003) 3337–3340
ture was stirred at room temperature for the appropriate
Acknowledgements
time (see Table 1). After completion of the reaction as
indicated by TLC, the ionic liquid was extracted with
One of the authors, G.C., is thankful to IICT, Hydera-
bad for the award of a Research Fellowship.
Et O. The ether layer was washed with aqueous 2N
2
NaOH, extracted, dried (Na SO ), concentrated in vacuo
2
4
and the crude product purified by silica gel column
chromatography to furnish the corresponding thioacetal.
1
Spectroscopic data; Compound 4b; H NMR (300 MHz;
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3
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1
12
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1
Spectroscopic data of [bmim][PF
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6
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