A convenient and efficient protocol for the synthesis of acylals catalyzed by Br?nsted acidic ionic liquids under ultrasonic irradiation

Article abstract of DOI:10.1016/j.ultsonch.2011.03.022

The synthesis of acylals (1,1-diacetates) via the reactions of aldehydes with acetic anhydride was carried out in 85-97% yields at room temperature under ultrasound irradiation catalyzed by the Br?nsted acidic ionic liquid [bmpy]HSO₄. This method provides several advantages, such as solvent-free conditions, operational simplicity, higher yields, and reduced environmental consequences. The ionic liquid was recovered and reused.

Full text of DOI:10.1016/j.ultsonch.2011.03.022

Ultrasonics Sonochemistry 18 (2011) 928–931
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Short Communication
A convenient and efficient protocol for the synthesis of acylals catalyzed
by Brønsted acidic ionic liquids under ultrasonic irradiation
⇑
Sanjay P. Borikar, Thomas Daniel
Division of Organic Chemistry, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of acylals (1,1-diacetates) via the reactions of aldehydes with acetic anhydride was carried
out in 85–97% yields at room temperature under ultrasound irradiation catalyzed by the Brønsted acidic
ionic liquid [bmpy]HSO . This method provides several advantages, such as solvent-free conditions,
4
operational simplicity, higher yields, and reduced environmental consequences. The ionic liquid was
recovered and reused.
Received 18 September 2010
Received in revised form 18 March 2011
Accepted 18 March 2011
Available online 12 April 2011
Ó 2011 Elsevier B.V. All rights reserved.
Keywords:
Ionic liquid
1
-Butyl-3-methylpyridinium hydrogen
sulfate
,1-Diacetates
1
Acylals
Solvent-free
Ultrasonic irradiation
1
. Introduction
Selective protection and deprotection of aromatic or aliphatic
of a simple, efficient and green method for the synthesis of acylals
is essential.
In recent years, the use of ultrasound in organic transformation
is well known to enhance reaction rates and yields/selectivity of
reaction. In several cases, it facilitates organic transformation at
ambient conditions which otherwise require drastic conditions of
temperature and pressure [16,17]. Ionic liquids (ILs) act as environ-
mentally benign green solvents as well as catalysts in many mod-
ern synthetic organic transformations [18]. Brønsted acidic ionic
liquids have the advantageous characteristics of both solid acids
and mineral liquid acids. They are designed to replace customary
mineral liquid acids like sulfuric acid and hydrochloric acid in
chemical procedures [19,20]. Recent demand for eco-friendly
chemical processes has led to the development of several clean
and efficient protocols [21]. Further, developments towards safe,
high-yielding and practical methods for the synthesis of acylals
are required.
carbonyl groups are extremely important in organic chemistry,
essentially because of its application in various multistep synthe-
ses [1]. In various ketones, the chemo-specific protection of one
carbonyl in 1,3-diones has great importance because of its involve-
ment in various natural product syntheses [1]. Acylals are synthet-
ically useful protecting groups for aldehydes because they are
stable under both neutral and basic media as well as acidic condi-
tions [2]. They are also easily converted into parent aldehydes [3].
Further, they are used as substrates in nucleophilic substitution
reactions [4] and are precursors of 1-acetoxydienes [5] for Diels–
Alder reactions. Compounds bearing the acylals functionality find
industrial applications as cross linking agent for cellulose in cotton
[
6] and activators in the composition of bleaching mixture for
wine-stained fabrics [7]. Some of the numerous methods for the
synthesis of acylals have been reported using NBS [8], CAN [9],
In continuation of our investigations on the development of
new synthetic methodologies [22,23], we wish to report a simple
and efficient method for the preparation of Brønsted acidic ILs
(
[
H
P
6 2
W
18
O
62ꢀ24H
12], boric acid [13], ferrous methanesulfonate [14] and anhyd.
[15]. The existing methodologies have convenient protocols
2 4
O) [10], silica sulfuric acid [11], [hmim]HSO
CoBr
2
([bmpy]HSO
4
) (Scheme 1), which was further used for the synthe-
with good to high yields. The majority of the reported methods suf-
fer from drawbacks, such as prolonged reaction times, high tem-
peratures, the use of strong acid, the need of solvents, costly
catalysts, and the complexity of work-up. Thus, the development
sis of acylals under ultrasonic irradiation (Scheme 2).
2
. Methods
All chemicals were obtained from commercial sources and used
⇑
Corresponding author. Tel.: +91 020 25902574; fax: +91 020 25902326.
E-mail address: d.thomas@ncl.res.in (T. Daniel).
without further purification. The reactions were carried out in a
thermostated (30 ± 1 °C) ultrasonic cleaning bath (Branson 5200
1
350-4177/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2011.03.022

S.P. Borikar, T. Daniel / Ultrasonics Sonochemistry 18 (2011) 928–931
929
CH3
CH3
Br
CH3
Table 1
RBr
97% H SO
2
4
The effect of the amount of ILs on the yield of product 2a under ultrasound
irradiation.
HSO4
90 oC, 5h
Reflux
N
N
Bu
N
Bu
DCM, 48h
Entry
Substrate/IL, molar ratio
Time (min)
Yield (%)a
1
2
3
1:0.05
1:0.1
1:0.2
7
5
4
92
97
86
Scheme 1. Preparation of 1-butyl-3-methylpyridinium hydrogen sulphate
[bmpy]HSO ).
(
4
a
The yields refer to the isolated products.
O
Table 2
Acylals reaction of benzaldehyde with acetic anhydride in various solvents.
1
0 mol% IL
OCH3
OCH3
R
R-CHO + Ac O
2
o
Solventa
Yield (%)b
Entry
Time (min)
)
)))), 30
C
1
2
3
4
5
Dichloromethane
Diethylether
Ethyl acetate
DMF
15
25
30
25
5
75
55
60
56
97
O
1
2
R = aryl and alkyl
Solvent-free
a
Scheme 2. Conversion of aldehydes to acylals under ultrasonic irradiation.
The reaction was carried out in 2 mL of solvents under ultrasonic irradiation.
The yields refer to the isolated products.
b
E4) at 50 kHz. Acetic anhydride was distilled before use. Thin layer
chromatography was carried out using silica 60F-245 plates. The
2.2.2. Compound 2c
1
13
H and C NMR spectras were recorded in CDCl
3
using a Bruker
1,1-Diacetoxy-1-(3-nitrophenyl) methane, faint yellow solid,
1
AVANCE 200 (200 MHz) spectrometer using TMS as internal stan-
dard. Melting points were determined using a Büchi 535 melting
point apparatus. Mass spectra were obtained using Shimadzu
GCMS-QP 5050 with electron impact ionization.
m.p. 64–65 °C; H NMR (200 MHz, CDCl ): d 8.40 (t, J = 7.96 Hz,
3
1H), 8.25 (d, J = 8.21 Hz, 1H), 7.82 (d, J = 7.70 Hz, 1H), 7.73 (s,
1H), 7.61 (t, J = 7.96 Hz, 1H), 2.16 (s, 6H). C NMR (50 MHz, CDCl ):
d 168.51, 148.22, 137.42, 132.86, 129.69, 124.46, 121.76, 88.23,
1
3
3
2
0.63 ppm.
2
.1. Preparation of 1-butyl-3-methylpyridinium hydrogen sulphate
2
.2.3. Compound 2f
(
[BMPy]HSO ) ionic liquid
4
1
,1-Diacetoxy-1-(4-bromophenyl) methane, white solid, m.p.
1
9
3
2–94 °C; H NMR (200 MHz, CDCl ): d 7.63 (s, 1H), 7.53 (d,
To a stirred solution of [bmpy]Br (5.0 g, 86.9 mmol) in 25 mL
dry CH Cl at 0 °C was added dropwise 97% H SO (1.15 mL,
6.9 mmol) over 10 min. The resulting solution was refluxed for
8 h. The solution was washed with water (3 ꢁ 5 mL) and dried
SO . The solvent CH Cl was distilled off under reduced
pressure to give pure IL [bmpy]HSO as a blackish viscous liquid
13
J = 8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 2.13 (s, 6H). C NMR
50 MHz, CDCl ): d 168.57, 134.39, 131.68, 128.32, 123.83, 88.99,
0.69 ppm.
2
2
2
4
(
2
3
8
4
over Na
2
4
2
2
2
.2.4. Compound 2j
,1-Diacetoxy-3-phenylprop-2-ene, white solid, m.p. 85–86 °C;
H NMR (200 MHz, CDCl ): d 7.39 (d, J = 6.9 Hz, 1H), 7.28–7.34
4
1
(
5.3 g; 98.7%).
1
3
(
2
m, 5H), 6.83 (d, J = 15.4 Hz, 1H), 6.24 (dd, J = 15.4, 6.80 Hz, 1H),
1
3
3
.15 (s, 6H). C NMR (50 MHz, CDCl ): d 168.59, 135.59, 135.21,
2
.2. General procedure for the synthesis of acylals under ultrasonic
1
28.82, 128.66, 127.03, 121.83, 89.76, 20.85 ppm.
irradiations
2
.2.5. Compound 2o
,1-Diacetoxy-piparane, white solid, m.p. 78–79 °C; 1H NMR
200 MHz, CDCl ): d 7.56 (s, 1H), 6.95–7.02 (m, 2H), 6.82 (d,
J = 8.46 Hz, 1H), 5.98 (s, 2H), 2.11 (s, 6H). C NMR (50 MHz,
CDCl ): d 168.46, 148.48, 147.65, 129.09, 120.68, 107.88, 106.70,
01.19, 89.40, 20.54 ppm.
A solution of aldehyde 1 (1.0 mmol) in freshly distilled Ac
3.0 mmol) was sonicated under ultrasound irradiation in the pres-
ence of a catalytic amount of [bmpy][HSO ] (10 mol%) at room
2
O
1
(
(
3
4
1
3
temperature. The mixture was irradiated for the period as indi-
cated in Table 2. The completion of reaction was monitored by
TLC (n-hexane–EtOAc, 9:1). After the completion of the reaction,
3
1
water was added and extracted with CH
2 2
Cl , washed with aq. NaH-
CO and dried over Na SO . The solvent was removed by evapora-
3
2
4
3. Results and discussion
tion under reduced pressure to afford the corresponding crude
products 2, which was then purified by column chromatography
on silica gel. The pure products were characterized by spectral data
In order to improve the yield, the effects of the catalyst on the
reaction of benzaldehyde with acetic anhydride were examined
under ultrasound irradiation. As shown in Table 1, when the molar
ratio of substrate to IL was increased from 1:0.05 to 1:0.1, higher
yield (97%) was achieved in approximately the same reaction time
1
13
(
H NMR and C NMR) and their physical characteristics were
compared with the literature data. The spectral data for some
products are given below:
(
Entry 2). When the molar ratio was increased to 1:0.2, the conver-
sion was completed in 4 min, but the yield was reduced to 86%
(Entry 3). The results showed that changing the molar ratio of sub-
strate with IL had a significant effect on the yield of product, and
the optimum molar ratio of substrate and IL was 1:0.1.
In order to verify the effect of solvents, we have performed the
reaction of benzaldehyde with acetic anhydride using different
2
.2.1. Compound 2a
,1-Diacetoxy-1-phenyl methane, white solid, m.p. 43–44 °C;
H NMR (200 MHz, CDCl ): d 7.67 (s, 1H), 7.29–7.45 (m, 5H), 1.92
): d 168.64, 135.65, 129.69,
1
1
3
1
3
(
1
s, 6H). C NMR (50 MHz, CDCl
28.61, 126.65, 89.76, 20.74 ppm.
3

9
30
S.P. Borikar, T. Daniel / Ultrasonics Sonochemistry 18 (2011) 928–931
conventional solvents under ultrasound irradiation. We observed
that the yields of the reaction under solvent-free conditions are
higher and the reaction time is shorter as compare to conventional
method (Table 2).
In this reaction, ionic liquids play the dual role of solvent as well
as promoter. In order to verify the effect of ultrasound irradiation,
we have performed the reaction of benzaldehyde and acetic anhy-
similar or higher than those described in the literature [8–15]. It
is also worth noting that the electronic effects of substituents on
the benzene ring seem to have an effect on product yield. We
examined, the reaction of 3-hydroxybenzaldehyde under above
conditions; and observed that both carbonyl and phenolic –OH
groups were acylated (Table 3, Entry 7). No diacetate formation
was observed for acetophenone under the same condition (Table
3, Entry 16). 4-(Dimethylamino) benzaldehyde failed to give acyl-
als under the same conditions, which may be due to the electron
donating of dimethylamino group (Table 3, Entry 13). The reaction
rate was found to be dependent on steric crowding surrounding
the aldehydes group. Thus, the combined steric effects of the peri
hydrogen and the 4-methoxy group made the reaction faster than
the 2,3,4-trimethoxy benzaldehyde (Table 3, Entries 8 and 9). The
reactions did not proceed in the absence of ionic liquid even under
heating conditions and required longer reaction times (10–12 h).
The reusability of the ionic liquid was also investigated. After
each run, water was added to the reaction mixture and product
4
dride catalyzed by [bmpy]HSO ionic liquid by stirring in the
absence of sonication. The yield of 1,1-diacetoxy-1-phenyl meth-
ane 2a was obtained in 75%, while under ultrasound, 2a was ob-
tained in 97% yield (Table 3, Entry 1).
From the above results, a typical experimental procedure was
chosen: aldehydes (1, 1.0 mmol), acetic anhydride (3.0 mmol)
and [bmpy]HSO (10 mol%). Using this system, we did a series of
4
experiments to prepare 1,1-diacetates under ultrasound irradia-
tion and the results were summarized in Table 3.
As shown in Table 3, the reaction of aldehydes with acetic anhy-
dride affords product 2 in excellent yields, which are, in general,
2 2
was extracted with CH Cl . The ionic liquid can be recovered from
the aqueous phase. The water was evaporated and the catalyst was
dried at 70 °C under reduced pressure for 2–3 h and reused in the
same reaction, which gave 97%, 95% and 90% yields, respectively.
The results demonstrate that the catalyst can be reused three
times, although the activity of the catalyst gradually decreased.
Table 3
Conversion of acylals in the presence of Brønsted acidic ionic liquid under ultrasonic
irradiation solvent-free conditions.
a
Yield (%)b
Entry Aldehyde R
Product Time (min)
Mp (°C)
This shows that Brønsted acidic ionic liquid ([bmpy]HSO
effective and reusable catalyst for the synthesis of acylals.
4
]) is an
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
Ph
2-NO
3-NO
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
5
8
7
4
6
5
15
8
6
7
10
8
120
5
25
120
97
94
91
95
92
94
91
92
92
96
95
93
0
43–44
84–86
64–65
81–83
49–51
92–94
77–78
113–115
63–64
85–86
89–91
90–91
Oil
2
C
C
6
H
H
4
The mechanism of this reaction involves either intermolecular
or intramolecular transfer of the second acetate group after initial
attack by acetic anhydride as shown in Scheme 3. The role of the
catalyst i.e., the Brønsted acidic IL, is to protonate the carbonyl
group of the aldehydes in order to increase the electrophilicity of
the functional group.
Compared with other reported methods, we can deduce that the
present method represented a better reaction procedure with the
main advantages of operational simplicity, recyclable and reusable
ILs, higher yields, milder reaction conditions and reduced environ-
mental consequences, which make it a useful and attractive pro-
cess for the synthesis of these compounds.
2
6
4
4-ClC
4-FC
4-BrC
3-HOC
3,4,5-(MeO)
4-MeOC
Cinnamyl
5-Me-furyl
4-HO,3-MeO-C
4,4 -Me
Hexyl
Piperonyl
Acetophenone
6
H
4
6
H
4
6
H
4
6
H
4
3 6 2
C H
6
H
4
1
1
1
1
1
1
1
6
H
3
0
2
NC
6
H
4
85
92
0
Oil
78–91
Oil
a
In conclusion, we have demonstrated a simple and efficient
method for the synthesis of acylals catalyzed by Brønsted acidic
Ratio aldehyde/acetic anhydride/IL = 1:3:0.1.
Isolated yields.
b
CH3
CH3
+
H
H
O
O
2
-
-
.
SO4
+
HSO
4
N
Bu
R
H
N
Bu
R
1
O
O
+
+
+
H
O
O
OH
O
CH3
CH3
OH
O
CH
3
O
H
H
+
H C
O
CH3
R
O
R
O
CH
3
R
H
3
O
CH3
+
H
R
O
O
H+
H
-
OAc
OAc
O
CH3
R
H
2
CH3
SO4
CH3
H+
2-
-
+
HSO4
N
N
Bu
Bu
Scheme 3. Plausible mechanism.

S.P. Borikar, T. Daniel / Ultrasonics Sonochemistry 18 (2011) 928–931
931
ionic liquid under ultrasonic irradiation at room temperature. Ionic
liquid acts as both solvent as well as catalyst. The advantages
include recyclable and reusable ILs, low cost, short reaction times,
excellent yields and high selectivity.
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[
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[
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The financial support from the Department of Science and Tech-
nology (DST), New Delhi is gratefully acknowledged. We are grate-
ful to Dr. Ganesh Pandey for his support and encouragement.
[
[
[
[
[
[
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