Rapid and efficient method for the synthesis of acylals from aldehydes and their deprotection catalyzed by p-Toluene Sulphonic Acid (p-TSA)

Article abstract of DOI:10.1080/00397910701239015

A simple, rapid, and efficient method has been developed for the synthesis of acylals from aldehydes using acetic anhydride in the presence of a catalytic amount p-TSA at 25°C, and the deprotection of acylals using water and catalytic p-TSA under microwave irradiation has been achieved in excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701239015

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Rapid and Efficient Method for the Synthesis
of Acylals from Aldehydes and Their
Deprotection Catalyzed by p‐Toluene
Sulphonic Acid (p‐TSA)
Krishnappa Manjula a & Mohamed Afzal Pasha a
a Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Published online: 11 May 2007.
To cite this article: Krishnappa Manjula & Mohamed Afzal Pasha (2007): Rapid and Efficient Method for the
Synthesis of Acylals from Aldehydes and Their Deprotection Catalyzed by p‐Toluene Sulphonic Acid (p‐TSA),
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:9, 1563-1569
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Synthetic Communicationsw, 37: 1563–1569, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701239015
Rapid and Efficient Method for the
Synthesis of Acylals from Aldehydes and
Their Deprotection Catalyzed by p-Toluene
Sulphonic Acid (p-TSA)
Krishnappa Manjula and Mohamed Afzal Pasha
Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Abstract: A simple, rapid, and efficient method has been developed for the synthesis of
acylals from aldehydes using acetic anhydride in the presence of a catalytic amount
p-TSA at 258C, and the deprotection of acylals using water and catalytic p-TSA
under microwave irradiation has been achieved in excellent yields.
Keywords: acylals, aldehydes, microwave irradiation, p-TSA, solvent-free condition
Selective protection and deprotection of carbonyl groups are of great
importance in synthetic organic chemistry. In the past decade, 1,1-diacetates
have received increasing attention, because these compounds are precursors[1]
for synthetically useful acetoxy dienes and di-halovinyl acetates. In
addition, acylals are useful in the nucleophilic substitution reactions.[2]
Furthermore, 1,1-diacetates have been applied as cross-linking reagents for
cellulose in cotton and serve as activators in the composition of the
bleaching mixture used for the treatment of wire-strained fabrics.[3] The prep-
aration of acylals were carried out using several catalysts such as protic[4] or
Lewis acids,[5] iodine,[6] NBS,[7] and metal salts such as LiBF4,[8a]
[8c]
[8d]
AlPW12O40,[8b] Bi(NO3)3 5H2O,
.
H6P2W18O62 24H2O.
Bi(OTf)3 xH2O or Li(OTf),
and
.
.
In addition, montmorillonite K-10[9] and
[8e]
Received in India September 28, 2006
Address correspondence to Mohamed Afzal Pasha, Department of Studies in
Chemistry, Central College Campus, Bangalore University, Bangalore 560 001,
India. E-mail: m_af_pasha@yahoo.co.in
1563

1564
K. Manjula and M. A. Pasha
zeolites[10] have been used for the purpose. Even though methods have been
developed for the protection of aldehydes as their diacetates, a limited
number of methods are available for deprotection of 1,1-diacetates to
aldehydes. Use of strong acids such as sulfuric acid or hydrochloric acid,[11]
boron-tri-iodide-N,N-diethyl aniline complex,[12] TiO2/SO4,[13] montmorillo-
[16]
[17]
nite clay,[14] neutral alumina,[15] and recently graphite
and AlCl3
has
been documented in the literature for the deprotection of 1,1-diacetates.
However, none of these methods claimed to give protection as well as depro-
tection except zeolite Y,[18] zirconium sulfophenyl phosphonate,[19] and ceric
ammonium nitrate.[20] The reported methods entail low yields, long reaction
times, corrosivity, and difficult workup and require thermal activation
before use. The reactions are carried out in harmful chlorinated solvents and
expensive reagents and demand an inert atmosphere.
In continuation of our research on solvent-free and microwave irradiation
reactions,[21] herein we report a rapid and efficient method for the synthesis of
acylals from aldehydes and acetic anhydride under solvent-free condition at
258C and regeneration of aldehydes in aqueous CH3CN from the respective
1,1-diacetates under microwave irradiation using a catalytic amount of inex-
pensive and readily available p-TSA within a minute in excellent yields
(Scheme 1).
To optimize the reaction conditions, initially we tried to convert benzal-
dehyde (1 mmol) to the corresponding acylals with p-TSA (0.1 mmol) and
acetic anhydride (2 mmol) in the presence of various solvents and also
under solvent-free condition. As shown in Table 1, in comparison to conven-
tional methods, the yield of the products under solvent-free conditions is
greater and the reaction time is much less. Therefore, we employed solvent-
free conditions for conversion of various aldehydes to the corresponding
acylals (Table 2).
By using this catalyst, aldehydes having electron-releasing or electron-
withdrawing groups were converted to their corresponding diacetates in
excellent yields within a minute. Moreover, the protocol could also work
with a,ß-unsaturated aldehydes (Table 2, Entry 6). Ketones such as acetophe-
none and benzophenone did not give any acylals under the reaction conditions
even after 24 h (Table 2, entries 9 and 10).
As mentioned in the introduction, it is very important to selectively
protect the aldehyde moiety in the presence of a kenotic carbonyl group.
We reacted an equimolecular mixture of benzophenone and benzaldehyde
with a twofold excess of acetic acid in the presence of p-TSA, and the
Scheme 1.

Synthesis and Deprotection of Acylals
1565
Table 1. Conversion of benzaldehyde (1 mmol) to 1,1-diacetoxy-1-phenylmethane in
different solvents and under solvent-free conditions in the presence of p-TSA
(0.1 mmol)a
Entry
Solventb
Yield (%)c
Time (min)
1
2
3
4
5
6
CH2Cl2
MeCN
EtOAc
Et2O
88
75
60
65
80
94
10
10
15
15
Toluene
Solvent
free
10
40 s
aReaction was conducted by stirring with 2 mmol of Ac2O at room temperature.
bReaction was carried out in 5 mL of solvent at room temperature.
cYields refer to isolated pure products.
reaction mixture was worked up (after 12 h) to give the benzaldehyde 1,1-
diacetate (90% yield) and recover the unchanged benzophenone
(Scheme 2).
We next investigated the use of catalyst in the deprotection of acylals to
the corresponding aldehydes by treatment of acylals using a catalytic amount
of p-TSA in the presence of water–acetonitrile (1:1) under microwave
irradiation and found that a power level of 320 W is the most suitable one
for the reaction. By this method, aromatic and a,ß-unsaturated acylals
Table 2. Diacetoxylation of aldehydes using acetic anhydride in the presence of
catalytic p-TSA under solvent-free condition at 258C
Mp (8C)
Reaction
time (%)
Entry
Substrate (s)
Benzaldehyde
Yielda
Found
Reported
1
2
25
45
96
89
43–44
103–105
123–126
63–64
44–45[4b]
65–66[5c]
125–127[4b]
64–65[5c]
52–53[4b]
84–87[9]
m-Nitrobenzaldehyde
p-Nitrobenzaldehyde
m- Chlorobenzaldehyde
2-Furaldehyde
3
40
30
92
85
4
5
35
35
90
92
50–51
83–85
6
Cinnamaldehyde
p-Methoxybenzaldehyde
Vanillin
7
30
30
90
80
62–64
89–91
64–65[9]
8
90–91[4b]
9
10
Acetophenone
Benzophenone
24 h
24 h
ND
ND
aND: not detected.

1566
K. Manjula and M. A. Pasha
Scheme 2.
have been transformed into the corresponding aldehydes in high yields
(Table 3).
A plausible mechanism of the p-TSA catalyzed reaction is shown in
Scheme 3.
In conclusion, we have developed a rapid and efficient method for the
preparation of acylals from aldehydes using acetic anhydride in the
presence of a catalytic amount of inexpensive and readily available p-TSA
without using any solvent at 258C, and we have also demonstrated that the dia-
cetates can be deprotected to the corresponding aldehydes using a catalytic
amount of p-TSA and water–acetonitrile under microwave irradiation in
excellent yields within a minute.
Table 3. Deprotection of acylals in the presence of catalytic p-TSA and 1:1
H2O–CH3CN under microwave irradiation
Bp (torr) or mp (8C)
Reaction
time (s) Yield (%)
Entry
1
Substrate
Found
Reported
1,1-Diacetoxy-1-phenyl
methane
25
30
35
40
35
30
30
30
94
80
82
75
78
80
82
75
179–180 180–183a
2
3
4
5
6
7
8
1,1-Diacetoxy-1-(3-
nitrophenyl)methane
1,1-Diacetoxy-1-(4-
nitrophenyl)methane
1,1-Diacetoxy-1-(3-
chlorophenyl)methane
1,1-Diacetoxy-1-(2-
furyl)methane
56–57
103–105 104–106b
63–64
213–214a
160–162 161–163a
242–245
248b
115–117 118–120a
80–81
81–83b
57–59a
1,1-Diacetoxy-3-phenyl-
prop-2-ene
1,1-Diacetoxy-1-(4-
methoxyphenyl)methane
1,1-Diacetoxy-1-(4-
hydroxy-3-methoxyphe-
nyl)-methane
aAldrich Handbook of Fine Chemicals.
bLancaster Research Chemicals, 2002–2003.

Synthesis and Deprotection of Acylals
1567
Scheme 3.
EXPERIMENTAL
All aldehydes, p-TSA, and solvents are purchased from BDH/Merck, s.d. fine
chemicals, and all the aldehydes and solvents were distilled before use.
Synthesis and deprotection of 1,1-diacetates were carried out at room tempera-
ture using a conventional (unmodified) household microwave oven (LG, Little
Cheff, 230 V, ꢀ50 Hz). Reactions were monitored by thin-layer chromato-
graphy (TLC) by comparison with the authentic samples. Melting and
boiling points were taken in open capillaries using a paraffin bath, and correc-
tions are applied wherever necessary.[22] Infrared spectra were recorded using
KBr pellets for solids and neat for liquids on Nicolet 400D FT-IR spectropho-
tometer. Yields refer to the isolated yields of the products after purification by
silica-gel chromatography.
General Procedure for the Protection of Aldehydes to Acylals
A mixture of aldehyde (1 mmol), acetic anhydride (2 mmol), and p-TSA
(0.1 mmol, 0.19 g) was stirred at room temperature for the time specified in
Table 2. The reaction was followed by TLC (ethyl acetate–light petrol 1:9).
After completion of the reaction, the mixture was diluted with Et2O. The
organic layer was washed with aqueous NaHCO3 (5 mL Â 2) and water
(5 mL) and dried over anhydrous sodium sulphate. Evaporation of the

1568
K. Manjula and M. A. Pasha
solvent under reduced pressure gave almost pure 1,1-diacetate. Further purifi-
cation by column chromatography gave the corresponding pure product.
General Procedure for the Conversion of Acylals to Aldehydes
A mixture of diacetate (1 mmol), p-TSA (0.1 mmol, 0.19 g), and water in
CH3CN (1:1, 1 mL) was irradiated in a commercial microwave oven
(320 W) for the time specified in Table 3. The reaction was monitored on
TLC (ethyl acetate–light petrol 1:9). At the end of irradiation, the mixture
was cooled to room temperature and extracted with diethyl ether. The
organic layer was washed with aqueous NaHCO3 (5 mL Â 2) and water
(5 mL) and dried over anhydrous sodium sulphate. The residue obtained
was column chromatographed over silica gel to obtain the pure aldehyde.
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