Deprotection of acetals and ketals by silica sulfuric acid and wet SiO 2

Article abstract of DOI:10.3390/71000751

Neat chlorosulfonic acid reacts with silica gel to give silica sulfuric acid in which sulfuric acid is immobilized on the surface of silica gel via covalent bonds. A combination of silica sulfuric acid and wet SiO₂ was used as an effective deacetalizating agent for the conversion of acetals to their corresponding carbonyl derivatives under thermal conditions.

Full text of DOI:10.3390/71000751

Molecules 2002, 7, 751-755
molecules
ISSN 1420-3049
http://www.mdpi.org
Deprotection of Acetals and Ketals by Silica Sulfuric Acid and Wet SiO2
,
1
2
3
BiBi Fathemeh Mirjalili , Mohamad Ali Zolfigol* and Abdolhamid Bamoniri
1
Department of Chemistry, College of Science, Yazd University, Yazd, Iran
Department of Chemistry, College of Science, Bu-Ali Sina University, Hamadan 65174, P.O. Box
2
4135, Iran.
3
Department of Chemistry, College of Science, Kashan University, Kashan 51167, Iran.
*
Author to whom correspondence should be addressed; e-mail: Zolfi@basu.ac.ir
Received: 25 October 2001; in revised form: 13 October 2002; / Accepted: 14 October 2002 /
Published: 31 October 2002
Abstract: Neat chlorosulfonic acid reacts with silica gel to give silica sulfuric
acid in which sulfuric acid is immobilized on the surface of silica gel via
covalent bonds. A combination of silica sulfuric acid and wet SiO2 was used as
an effective deacetalizating agent for the conversion of acetals to their
corresponding carbonyl derivatives under thermal conditions.
Keywords: Silica sulfuric acid, Deacetalization.
Introduction
Acetals are widely used as protecting groups in organic synthesis and, as a consequence, many
methods have been examined for both their formation and removal [1,2]. Typically, deprotection of
acetals requires the use of protic [3] or Lewis acids [4], iodotrimethylsilane [5], cobalt or manganese
salts in the presence of air or O2 [6] pyridinium tosylate [7], montmorillonite K10 [8], cerium
ammonium nitrate(CAN) [9], etc.
On the other hand, any reduction in the amount of sulfuric acid needed and/or any simplification in
handling procedures is desirable for risk reduction, economic advantages and environmental protection
[10]. In addition, there is current research and general interest in heterogeneous systems because of the

7
52
Molecules 2002, 7
importance such systems have in industry and in developing technologies [11]. In continuation of our
studies on the application of inorganic acidic salts [12] we have found that silica gel reacts with
chlorosulfonic acid to give silica sulfuric acid (I). It is interesting to note that the reaction is easy and
clean without any work-up procedure because HCl gas is evolved from the reaction vessel immediately
(Scheme 1).
Scheme 1
rt.
SiO2 OH + ClSO H (neat)
SiO2 OSO H + HCl
3
3
I
We hoped that the silica sulfuric acid (I) would be a superior proton source to all of the reported
acidic solid supports or acidic resins such as polystyrene sulfonic acid and Nafion-H [13] for running
reactions under heterogeneous conditions. Here we wish to report a convenient method for the
deacetalization of acetals by using silica sulfuric acid (I) and wet SiO 2 (II) under thermal conditions
(Scheme 2).
Results and Discussion
Different types of acetals and ketals (1) were subjected to the deacetalization reaction in the
presence of silica sulfuric acid and wet SiO2 (60% w/w) under thermal conditions with quantitative
yields. We used toluene as a solvent at 60-70 C. The results of deacetalization reactions are shown in
Table 1.
Scheme 2
R3
O
O
SiO - OSO H
O
R1
2
3
R4
R2
Wet SiO (60%)
2
O
R2 R1
Toluene, 60-70 C
1
2
Conclusions
Silica sulfuric acid is an excellent proton source for acetal deprotection reactions in terms of
convenience, cheapness, easy production and insolubility to all of organic solvents. The cheapness and
availability of the reagents, easy procedure and work-up make this method attractive for large scale
operations.

7
53
Molecules 2002, 7
Table 1: Deprotection of Acetals and Ketals in Toluene at 60-70 C
Substrate
Time
(min)
Yield
(%)
Entry
Substrate
Product
(
mmole) / I (g) / II (g)
CH3
O
O
1
1
1
1
a
b
c
0.2 / 0.12 / 0.2
0.35 / 0.1 / 0.1
0.26 / 0.25 / 0.27
0.25 / 0.2 / 0.2
60
60
60
60
75
95
94
98
93
94
CH3
O
Cl
Cl
H
O
O
O
H
H
CH3
H C
3
H
O
O
O
O
O N
O N
2
2
H
O
d
O
H
H
HO
HO
H
O
O
HO
O
0.25 / 0.2 / 0.2
HO
HO
1e
HO
H
O
H
1
f
OMe
0.3 / 0.11 / 0.15
0.25 / 0.3 / 0.3
0.2 / 0.3 / 0.3
0.25 / 0.3 / 0.3
0.25 / 0.4 / 0.4
0.25 / 0.3 / 0.3
60
60
60
75
60
60
97
98
97
95
98
96
OMe
H
O
O
H
1
1
g
O
NO2
O N
2
O
H
OCH3
H CO
3
H
H
h
O
O
OH
HO
HO
O
H
O
1
i
O
OH
O
CH3
1
j
O
O
CH3
NO2
O N
2
O
H
O
O
H
1
k
Cl
Cl

7
54
Molecules 2002, 7
O
H
1
l
O
H
O
Br
Br
0
.25 / 0.3 / 0.3
60
60
98
97
O
H
H
OH
1m
O
0.25 / 0.3 / 0.4
O
OH
Acknowledgments
Financial support for this work by the Office of Research Affairs, Yazd University, Yazd, Iran and
also Bu-Ali Sina University, Hamadan, Iran, are gratefully acknowledged.
Experimental
General
Chemicals such as carbonyl compounds, ethylene glycol, chlorosulfonic acid and silica gel were
purchased from the Fluka, Merck and Aldrich chemicals companies. Acetals and 5-norbornene-2,2-
dimethylol were synthesized according to the our previously reported procedure [1]. The
1
deacetalization products were characterized by comparison of their spectral (IR, H-NMR), TLC and
physical data with the authentic samples. Silica sulfuric acid was prepared according to our very
recently reported procedure as follows [14].
Preparation of silica sulfuric acid
A 500 mL suction flask equipped with a constant-pressure dropping funnel and a gas inlet tube for
conducting HCl gas over an adsorbing solution (i. e. water) was used. It was charged with silica gel
(60.0 g). Chlorosulfonic acid (23.3 g, 0.2 mol) was added dropwise over a period of 30 min at room
temperature. HCl gas evolved from the reaction vessel immediately (Scheme 1). After the addition was
complete the mixture was shaken 30 min. A white solid (silica sulfuric acid) 76.0 g was obtained.
Typical procedure for deacetalization of acetals (1) to the corresponding aldehydes (2): Preparation of
4
-nitrobenzaldehyde(2g).
A mixture of 1g (0.07 g, 0.25 mmol), silica sulfuric acid (I) (0.3 g) and wet SiO2 (60% w/w, 0.3 g)
in toluene (3 mL) was heated at 60-70 C for 60 minutes. Then the solvent was removed under reduced
pressure. The product, 4-nitrobenzaldehyde (2 g), was obtained in quantitative yield by addition of
ethanol and water.

7
55
Molecules 2002, 7
References
1
2
3
. Pourjavadi, A.; Mirjalili B. F. J. Chem. Res. 1999, 562.
. Firouzabadi, H. Iranpour, N.; Zolfigol, M. A. Bull. Chem. Soc. Jap. 1998, 71, 2169.
. Green, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis; John Wiley and Sons, Inc.:
New York; 1991.
4
5
6
7
8
. Sen, S.E.; Roach, S.L.; Boggs, J.K.; Ewing, G.J.; Magrath, J. J. Org. Chem. 1997, 62, 6684.
. Butler,D.N.; Halton, B.; Warrener, R.N. Aus. J. Chem. 2000, 53, 561.
. Hashemi, M. M.; Kalantari, F. Synth. Commun. 2000, 30, 1857.
. Sterzycki, R. Synthesis, 1979, 724.
. Gautier, E.G.L.; Graham, A.E.; Mckillop, A.; Standen, S.P.; Taylor, R.J.K.; Tetrahedron Lett.
1
997, 38, 1881.
. Ates, A.; Gautier, A.; Leroy, B.; Plancher, J.M.; Quesnel, Y.; Marko, I.E.; Tetrahedron Lett. 1999,
0, 1799.
0. Riego, J.M.; Sedin. Z.; Zaldivar. J.M.; Marziano, N.C.; Tortato, C. Tetrahedron Lett. 1996, 37,
13.
9
1
4
5
11. Turro, N.J. Tetrahedron, 1987, 43, 1589.
1
2. (a) Zolfigol, M.A. Synth. Commun., 2000, 30, 1593; (b) Zolfigol, M.A.; Bagherzadeh, M.;
Chehardoli, G.; Mallakpour, S.E. ibid., 2001, 31, 1149; (c) Zolfigol, M.A.; Bagherzadeh, M.;
Ghorbani Choghamarani, A.; Keypour, H.; Salehzadeh, S. ibid., 2001, 31, 1661; (d) Zolfigol,
M.A.; Sadeghi, M.M.; Mohammadpoor-Baltork, I.; Ghorbani Choghamarani, A.; Taqian-nasab, A.
Asian J. Chem. 2001, 13, 887; (e) Zolfigol, M.A.; Bagherzadeh, M.; Madrakian, E.; Ghaemi, E.;
Taqian-nasab, A. J. Chem. Res. 2001, 140; (f) Zolfigol, M.A.; Ghaemi, E.; Madrakian, E.
Molecules, 2001, 6, 614; (g) Zolfigol, M.A.; Ghaemi, E.; Madrakian, E.; Kiany-Borazjani, M.
Synth. Commun., 2000, 30, 2057; (h) Zolfigol, M.A.; Madrakian, E.; Ghaemi, E. Indian J. Chem.,
2
000, 39B, 308; (i) Zolfigol, M.A.; Kiany-Borazjani, M.; Sadeghi, M.M.; Memarian, H.R.;
Mohammadpoor-Baltork, I. Synth. Commun., 2000, 30, 2945; (j) Zolfigol, M.A.; Kiany-Borazjani,
M.; Mallakpour, S.E.; Nassr-Isfahani, H. ibid., 2000, 30, 2573; (k) Zolfigol, M.A.; Kiany-
Borazjani, M.; Sadeghi, M.M.; Mohammadpoor-Baltork, I.; Memarian, H.R. ibid., 2000, 30, 3919;
(l) Zolfigol, M.A.; Kiany-Borazjani, M.; Sadeghi, M.M.; Memarian, H.R.; Mohammadpoor-
Baltork, I. J. Chem. Res. 2000, 197; (m) Salehi, P.; Khodaie, M.; Zolfigol, M.A.; Keyvan, A.
Synth. Commun., 2001, 31, 1947.
1
3. Olah, G.A; Molhotra, R.; Narang, S.C. J. Org. Chem. 1978, 43, 4628.
4. Zolfigol, M.A. Tetrahedron, 2001, 57, 9509.
1
Sample Availability: Samples of substrates 1c, 1g-1l and the 3-nitro and 4-cyano analogs of substrate
g are available from MDPI.
1
©
2002 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.