A rapid, convenient and chemoselective synthesis of acylals from aldehydes catalyzed by reusable nano-ordered MCM-41-SO3H

Article abstract of DOI:10.1016/j.crci.2012.06.014

Acylals were prepared by direct condensation of aldehydes with acetic anhydride using nano-ordered MCM-41-SO₃H as a heterogeneous catalyst under solvent-free conditions at room temperature in a very short reaction time and excellent yields. The catalyst is recyclable, non-toxic, neither air nor moisture sensitive, and easy to handle. High chemoselectivity toward aldehydes in the presence of ketones is another advantage of the present method which provides selective protection of aldehydes in their mixtures with ketones.

Full text of DOI:10.1016/j.crci.2012.06.014

C. R. Chimie 15 (2012) 1072–1076
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Full paper/M e´ moire
A rapid, convenient and chemoselective synthesis of acylals from
aldehydes catalyzed by reusable nano-ordered MCM-41-SO H
3
Hesam Tourani, Mohammad Reza Naimi-Jamal *, Mohammad Ghorban Dekamin,
Meysam Amirnejad
Research Laboratory of Green Organic Synthesis, Department of Chemistry, Iran University of Science and Technology, 16846 Tehran, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Acylals were prepared by direct condensation of aldehydes with acetic anhydride using
Received 26 April 2012
3
nano-ordered MCM-41-SO H as a heterogeneous catalyst under solvent-free conditions at
Accepted after revision 28 June 2012
Available online 11 August 2012
room temperature in a very short reaction time and excellent yields. The catalyst is
recyclable, non-toxic, neither air nor moisture sensitive, and easy to handle. High
chemoselectivity toward aldehydes in the presence of ketones is another advantage of the
present method which provides selective protection of aldehydes in their mixtures with
ketones.
Keywords:
Aldehydes
Acylation
ß 2012 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
3
MCM-41-SO H
Carbonyl protection
Solvent-free conditions
Heterogeneous catalysis
1
. Introduction
phosphoric acid [13], HClO
or a Lewis acid such as LiClO
NbCl [18], iron(III) fluoride [19], NBS [20], RuCl
[21], P /Al [22], SnCl /SiO [23], etc. Furthermore,
many inorganic heterogeneous catalysts such as mont-
morillonite clay [24], Amberlyst-15 [25], and AlPW12
[26] have been also used. Although in many cases the gem-
diacetates are obtained in good yields most of these
methods suffer from some disadvantages such as long
reaction time, tedious work-up procedure, the use of
homogenous catalysts or harmful solvents, and high
reaction temperature. Consequently, the development of
mild catalytic methods for the preparation of acylals is
still desirable.
4
–SiO
[16], Ti (IV) halides [17],
ꢀxH
2
[14], sulfamic acid [15]
4
During the synthesis of many molecules, especially in
5
3
2
O
drug synthesis, protection of a carbonyl group is often
necessary [1]. Different reagents have been employed for
this purpose such as alcohols [2], ethane dithiol [3],
trialkyl orthoformates [4], 2-mercaptoethanol [5], acetic
anhydride [6], etc. Among these protecting agents, acetic
anhydride is of special interest and has been widely used
for protection of carbonyl compounds, due to the stability
of gem-diacetates (acylals) in neutral and mild basic
conditions, as well as acidic medium [7]. Furthermore, the
diacetates serve as valuable precursors for the preparation
of 1-acetoxydienes [8], vinyl acetates [9], and arylnitriles
2
O
5
2
O
3
4
2
O
40
[
10], and cyanohydrin esters [11]. Usually diacetates are
In recent years, the use of heterogeneous catalysts has
been widely studied [27] because they are easily remov-
able from the reaction media by simple filtration after
completion of the reaction and in many cases they are
reusable. In order to overcome the lower reaction rate of
heterogeneous catalysts compared to homogeneous ones,
the use of high surface area materials such as MCMs, SBA,
and zeolites have been widely investigated [28].
prepared by condensation of aldehydes and acetic
anhydride in the presence of a protonic acid such as
1
-H-3-methyl-imidazolium hydrogen sulfate [12], silica
*
Corresponding author.
E-mail address: naimi@iust.ac.ir (M.R. Naimi-Jamal).
1
631-0748/$ – see front matter ß 2012 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2012.06.014

H. Tourani et al. / C. R. Chimie 15 (2012) 1072–1076
1073
MCM-41- SO
Solvent-free, rt
H
O
O
3
O
O
ArCHO
+
Ac O
RCH(OAc)2
2
O
O
O
O
O
Scheme 1. Solvent-free synthesis of acylals from aldehydes and acetic
anhydride catalyzed by nanoporous MCM-41-SO H.
O
3
O
O
We herein wish to report an efficient procedure for the
rapid synthesis of acylals from various aldehydes with
3i
3j
3
acetic anhydride using MCM-41-SO H as a heterogonous
catalyst under solvent-free conditions (Scheme 1).
Scheme 2. Acetylated products of salicylaldehyde (1i) and 4-
hydroxybenzaldehyde (1j).
2
. Results and discussion
Table 1, the best result was obtained when 5.0 mmol of 2
and 10 mg of the catalyst were used. It is notable that when
20 mg of catalyst was used, the yield of the desired product
decreased dramatically. This is presumably due to the
considerable protonation of acetic anhydride oxygen
atoms by acidic protons on the catalyst surface which
decreases their nucleophilic activity towards the carbonyl
group of aldehyde. Further experiments using optimized
conditions revealed that only 3 min is enough to complete
the model reaction affording 99% of the product 3c.
Encouragedbytheseresults, thescopeofthemethodwas
investigated with different aldehydes. The results have been
summarized in Table 2. As it is shown, different aromatic
aldehydes bearing both electron withdrawing (Entries 2–8)
and electron releasing groups (Entries 9–12) afforded the
corresponding acylals in high to excellent yields. The nature
and position of the substituents on the aromatic ring
strongly affected both reaction yield and required time for
the completion of the reaction. Therefore, electron donating
groups increased the required reaction time and afforded
lower yields compared to electron withdrawing groups. As a
consequence, 4-dimethylamino benzaldehyde (1m) was
not converted to the corresponding acylal, due to the strong
In order to optimize the amount of acetic anhydride and
the catalyst loading, the reaction of 4-chlorobenzaldehyde
1c) was studied as the model reaction at room tempera-
ture. Different amounts of acetic anhydride (2) (1.0, 3.0,
and 5.0 mmol) and MCM-41-SO H catalyst (0, 5, 10 and
0 mg) were investigated in the presence of 1.0 mmol 4-
chlorobenzaldehyde. The reaction progress was monitored
by GC. The mixture was then diluted with 5.0 mL CH Cl
and filtered. The organic layer was subsequently washed
with saturated 10% aqueous NaHCO solution and water,
and then dried over anhydrous Na SO . The solvent was
(
3
2
2
2
3
2
4
evaporated under reduced pressure and the solid crude
product was recrystallized from n-hexane:EtOH to afford
pure acylal 3c. The structure of the product was deter-
1
mined on the basis of its spectral data. The H NMR spectra
of the product showed a characteristic signal at about
.67 ppm for benzylic H. The results have been summa-
rized in Table 1. As it is shown, in the absence of the
catalyst no product was obtained, even in excess amount of
7
3
acetic anhydride. When MCM-41-SO H was added, differ-
ent yields of the desired product were obtained, depending
on the amount of the catalyst used. As it is obvious from the
Table 1
Optimization of the amount of acetic anhydride and the catalyst loading in the model reaction.
O
H
CH
3
O
O
CH
3
O
O
O
O
MCM-41-SO
Solvent-free
0 min, rt
3
H
+
CH3
O
CH3
3
Cl
Cl
1
c
2
3c
1
c
2
Catalyst
(mg)
Yield
(%)
(mmol)
(mmol)
1
.0
1.0
–
5
–
43
52
35
1
2
0
0
1
.0
3.0
5.0
–
5
1
2
–
75
82
60
0
0
1
.0
–
5
1
2
–
88
99
75
0
0

1
074
H. Tourani et al. / C. R. Chimie 15 (2012) 1072–1076
Table 2
a
MCM-41-SO
3
H catalyzed acetylation of aldehydes with acetic anhydride .
b
Entry
Substrate
Product
Time (min)
Yield (%)
Mp (8C) (ref)
1
2
3
4
5
6
7
8
9
Benzaldehyde
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
3
5
95
90
99
93
95
98
99
90
95
93
85
92
–
43–45 (44–45) [15]
56–58 (55–56) [29]
80–82 (80) [31]
2-Chlorobenzaldehyde
4-Chlorobenzaldehyde
2-Nitrobenzaldehyde
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
4-Cyanobenzaldehyde
4-Bromobenzaldehyde
Salicylaldehyde
3
3
89–90 (90–91) [15]
65–67 (65–66) [15]
124–126 (125–127) [15]
100–101 (100–101) [12]
94–95 (93–95) [12]
101–103 (101–103) [29]
93–94 (90–92) [12]
63–65 (63–64) [29]
80–82 (80–82) [12]
–
5
3
1g
1h
1i
3g
3h
3i
6
5
4
1
1
1
1
1
0
1
2
3
4
4-Hydroxybenzaldehyde
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
4-Dimethylaminobenzaldehyde
Cinnamaldehyde
1j
3j
6
1k
1l
3k
3l
5
5
1m
1n
3m
3n
180
10
85
83–84 (83–85) [29]
a
Reaction conditions: aldehyde (1 mmol), acetic anhydride (5 mmol), catalyst (0.01 g), solvent-free, and at room temperature.
Isolated yield.
b
electron donating nature of the amino group in accordance
with literature data [6,29] (Entry 13). Furthermore, steric
hindrance in 2-isomers may be the reason that theses
substrates required longer reaction time compared to their
The reusability of the catalyst was also investigated in
further runs of the model reaction. The filtered catalyst
after each run was washed several times with acetone and
ethanol and dried in an oven at 80 8C for 5 h. The results of
catalyst recyclability have been summarized in Fig. 1.
To investigate the chemoselectivity of this method, a
competition reaction between equimolar mixtures of some
aldehydes and similar ketones with acetic anhydride was
studied (Scheme 3). As it is shown, whereas aldehydes
were quantitatively converted to the corresponding
acylals, ketones remained practically intact.
4
-isomer (e.g. Entries 2 and 3).
This protocol also tolerated acid-sensitive
a,b-unsatu-
rated substrates such as cinnamaldehyde (1n, Entry 14)
which can polymerize under homogeneous acidic condi-
tions. Furthermore, when aldehydes bearing hydroxyl
group on aromatic ring (e.g. 1i and 1j) were used,
acetylation of the hydroxyl group was also observed
(
Scheme 2). The structure of these products was secured by
According to the obtained results, the following
mechanism can be proposed for protection of aldehydes
spectroscopic data. However some works have mistakenly
reported the same melting points for the acylals with free
hydroxyl group [30].
with acetic anhydride in the presence of MCM-41-SO
3
H
(Scheme 4).
In order to show the merit of the present work,
comparison of the catalytic activity of some homogeneous
and heterogeneous catalysts in the acylation reaction of 4-
nitrobenzaldehyde (1f) has been presented in Table 3. The
results clearly show the advantages of this method in
terms of the obtained yield of the desired product, reaction
time and catalyst loading. Whereas most of the reported
methods require reaction times in order of some hours to
be completed, the present method needs only 3 min to
afford the product 3f quantitatively.
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
5
run no.
Scheme 3. Competition reaction between equimolar mixtures of some
aldehydes and similar ketones with acetic anhydride.
Fig. 1. Reusability study of the catalyst in the model reaction.

H. Tourani et al. / C. R. Chimie 15 (2012) 1072–1076
1075
Table 3
Comparison of the present method with some reported methods in the acylation reaction of 1.0 mmol of 4-nitrobenzaldehyde.
Catalyst
Temp.
Time
Catalyst Loading
Yield (%)
LiOTf [32]
rt
15 h
11 h
4 min
8 h
20 mol%
10 mol%
10 mg
94
75
94
98
61
53
92
55
96
95
98
+
À
Ph
3
P CH
2
COMeBr [31]
rt
a
SPDTSA [33]
NBS [20]
rt
rt
10 mol%
20 mg
H
3
PW12
O
40/MCM-41 [34]
60 8C
rt
2 h
TiCl
SnCl
Mg(CH
Montmorillonite Clay in CCl
4
[17]
2.66 h
15 min
12 h
1 h
10 mol%
100 mg
1.5 mol%
20 mg
4
/SiO
SO
2
[23]
-HOAc [29]
rt
3
3
)
2
rt
4
[24]
rt
Amberlyst-15 in CH
This work
2
Cl
2
[25]
rt
1 h
500 mg
10 mg
rt
3 min
a
Silica-bonded propyl-diethylene-triamine-N-sulfamic acid.
H
O+
H
3
determined in CDCl at ambient temperature. Gas chro-
O
H
matograph was a Perkin Elmer GC 8400. Melting points
were determined using an electrothermal apparatus and
are uncorrected. All chemicals were purchased from Merck
or Aldrich and have been used as received, except for liquid
aldehydes which have been freshly distilled prior to use.
-
MCM-41-
SO
3
H
+
MCM-41-SO
3
+
O
H
OH O+
CH
3
O+
H
H
4.2. Typical procedure for synthesis of acylals
O
O
O
CH
3
+
CH
3
O
CH
3
Aldehyde (1.0 mmol), Ac
2
O (5.0 mmol) and MCM-41-
SO
3
H (10 mg) were poured in a 20 mL round bottom flask
and stirred magnetically at ambient temperature for an
appropriate time (Table 2). The reaction progress was
monitored by TLC (Hexane: EtOAc; 5:1) or GC. After
completion of the reaction, the mixture was diluted with
CH
3
CH3
O
O
+
H
O
OH O+
O
CH
O
O
O
O
3
H
H
H
CH
3
O
CH
3
O
CH
3
CH
saturated 10% aq. NaHCO
dried over anhydrous Na SO
Cl
2
and filtered. The organic layer was washed with
solution and water, and then
. The solvent was evaporated
2
H+
3
2
4
under reduced pressure and the solid crude was recrys-
tallized from n-hexane:EtOH to afford the pure solid
products. The structures of all products were determined
on the basis of their analytical and/or spectral data
comparing with the literature data (Table 2).
+
MCM-41-SO
3
+ H
3
MCM-41- SO H
Scheme 4. Proposed mechanism for acetalyzation of benzaldehyde
catalyzed by MCM-41-SO H.
3
4.3. General procedure for preparation of MCM-41
3
. Conclusion
In conclusion, a mild, efficient and recoverable hetero-
To 42 mL deionized water in a 500 mL beaker, 2.7 g
diethylamine was added at ambient temperature and
stirred. Then, 1.47 g cetyltributylammonium bromide
(CTAB) was gradually added to the above mixture until
a clear solution was obtained. Tetraethyl orthosilicate
(2.1 g) was added drop-wise to the solution and the pH was
fixed at 8.5 by addition of 1 M HCl solution. After 2 h, the
resulting solid product was filtered and washed several
times with deionized water, and dried at 45 8C for 12 h. The
obtained MCM-41 was calcined at 550 8C for 5 h to remove
all the surfactant [35].
geneous catalyst has been developed for the preparation of
gem-diacetates from aldehydes and acetic anhydride
under solvent-free conditions at room temperature. We
found that various aldehydes were converted to acylals
chemoselectively in high to quantitative yields and the
required reaction time was considerably shorter than
many of the previously described methods.
4
. Experimental
4
.4. General procedure for preparation of MCM-41-SO
3
H
4.1. Materials and methods
MCM-41 (1 g) was suspended in CH Cl (5 mL) in a
2
2
FT-IR spectra were recorded as KBr pellets on a
100 mL round bottom flask equipped with a gas outlet tube
and a dropping funnel containing a solution of chlor-
osulfonic acid (2 mL) in dichloromethane (15 mL). The
chlorosulfonic acid solution was added drop-wise to the
1
Shimadzu FT-IR- 8400S spectrometer.
H
NMR
(
5
500 MHz) Spectra were obtained using a Bruker DRX-
00 AVANCE spectrometer. All NMR spectra were

1
076
H. Tourani et al. / C. R. Chimie 15 (2012) 1072–1076
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3
.5. Physical and spectral data of selected products:
.5.1. Compound 3c
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[
(
White solid; mp 80–82 8C (Lit. [31] 80 8C); IR (KBr):
14] V.T. Kamble, V.S. Jamode, N.S. Joshi, A.V. Biradar, R.Y. Deshmukh,
À1
1
092, 1757, 1742, 1246, 1202, 1011 cm
): = 7.67 (s, 1 H), 7.48–7.50 (dd, J = 8.0,
.5 Hz, 1 H), 7.40–7.42 (dd, J = 8.0, 1.5 Hz, 1 H), 2.17 (s, 6 H).
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3
d
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1
4
.5.2. Compound 3i
White solid; mp 101–103 8C (Lit. [29] 101–103 8C); IR
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(
À1 1
KBr): 3040, 1747, 1495, 1373, 1250, 1211, 1192 cm ; H
(
[
NMR (500 MHz, CDCl
J = 8.0, 1.0 Hz, 1 H), 7.44–7.47 (m, 1 H), 7.30–7.34 (m, 1 H),
.14–7.16 (d, J = 8.0 Hz, 1 H), 2.37 (s, 3 H), 2.13 (s, 6 H).
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7
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We acknowledge Iran University of Science and Tech-
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Professor Gerd Kaupp from University of Oldenburg,
Germany for his kind donation of some chemicals.
5
(
6;
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