Chemoselective synthesis of 1,1-diacetates from aldehydes using anhydrous cobalt(II) bromide under solvent-free conditions

Article abstract of DOI:10.1080/00397910902985499

A mild and efficient method has been developed for the chemoselective preparation of 1,1-diacetates (acylals) from aldehydes catalyzed in the presence of a catalytic amount (0.1mmol) of anhydrous cobalt(II) bromide under solvent-free conditions. The remarkable selectivity under mild and neutral conditions, excellent yields, short reaction time, and easily available and inexpensive catalyst are important features of this method.

Full text of DOI:10.1080/00397910902985499

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Chemoselective Synthesis of 1,1-
Diacetates from Aldehydes Using
Anhydrous Cobalt(II) Bromide Under
Solvent-Free Conditions
Gangadhar A. Meshram a & Vishvanath D. Patil a
a Department of Chemistry , University of Mumbai , Vidyanagari,
Mumbai, India
Published online: 06 Jan 2010.
To cite this article: Gangadhar A. Meshram & Vishvanath D. Patil (2010) Chemoselective Synthesis of
1,1-Diacetates from Aldehydes Using Anhydrous Cobalt(II) Bromide Under Solvent-Free Conditions,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:3, 442-449, DOI: 10.1080/00397910902985499
To link to this article: http://dx.doi.org/10.1080/00397910902985499
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Synthetic Communications1, 40: 442–449, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902985499
CHEMOSELECTIVE SYNTHESIS OF 1,1-DIACETATES
FROM ALDEHYDES USING ANHYDROUS COBALT(II)
BROMIDE UNDER SOLVENT-FREE CONDITIONS
Gangadhar A. Meshram and Vishvanath D. Patil
Department of Chemistry, University of Mumbai, Vidyanagari, Mumbai,
India
A mild and efficient method has been developed for the chemoselective preparation of
1,1-diacetates (acylals) from aldehydes catalyzed in the presence of a catalytic amount
(0.1 mmol) of anhydrous cobalt(II) bromide under solvent-free conditions. The remarkable
selectivity under mild and neutral conditions, excellent yields, short reaction time, and easily
available and inexpensive catalyst are important features of this method.
Keywords: Chemoselective; cobalt dibromide; 1,1-diacetates; solvent-free
INTRODUCTION
Simple, efficient, environmentally benign, and economically viable chemical
processes or methodologies for widely used organic compounds are in great demand.
Diacetylation reactions of aldehydes to develop various useful organic compounds
have received considerable attention in organic synthesis. Selective protection and
deprotection of carbonyl groups are essential steps in modern organic chemistry.[1]
Protective group acylals are fairly stable under neutral and basic conditions[1b] as
well as under critically controlled acidic conditions. Apart from mere protective
groups, acylals are important synthons and useful precursors. The 1,1-diacetates
derived from a,b-unsaturated aldehydes are important starting materials in the
Diels–Alder reaction.[2] These 1,1-diacetates have several synthetic and industrial
applications and are used as cross-linking reagents[3] in cellulose and the cotton
industry and are also used as stain-bleaching agents. As synthons, their usefulness
has been exploited in well-known reactions of organic chemistry, such as the
Grignard,[4] Barbier,[4b] and Prins[5] reactions, and condensation reactions, such as
the Knoevenagel[6] and Benzoin[7] reactions. Because of their unique properties as
protective groups as well as important synthons, an efficient, mild, and facile prep-
aration of acylals is of current interest. Generally, acylals are prepared from alde-
hyde and acetic anhydride using strong protonic acids such as sulfuric,
phosphoric, methanesulfonic, or perchloric acids.[8] Use of strong Lewis acids[9] such
Received January 19, 2009.
Address correspondence to Gangadhar A. Meshram, Department of Chemistry, University of
Mumbai, Vidyanagari, Santacruz (E), Mumbai 400098, India. E-mail: vdp148@yahoo.com
442

1,1-DIACETATES FROM ALDEHYDES
443
Scheme 1. R: Alkyl, phenyl.
as BF3, PCl3, ZnCl2, LiBF4, ZrCl4, FeCl3, FeCl3=SiO2, Zn(ClO4)2 ꢀ 6H2O,
RuCl3 ꢀ xH2O, and SbCl3 have also been reported. Apart from these catalysts,
expensive[10] graphite, zeolite, tungstosilicic acid, and zirconium sulfophenyl phos-
phonate have also been employed in this protection process. Some of these methods
still suffer from drawbacks such as prolonged reaction time (viz., up to 120 h in the
case of 2-furyl aldehyde with PCl3), poor yields [in the case of 4-nitrobenzaldehyde
(4%) and cinnamaldehyde (30%) when PCl3 is used], and in some cases the require-
ment of elevated temperature. Several of these catalysts are not very safe to handle,
such as metal perchlorates and BF3. Consequently, it seems desirable and necessary
to develop a simple, safe, efficient, and facile method for the preparation of these
gemdiacetates. In this communication, we report that anhydrous cobalt(II) bromide
is an efficient and very mild catalyst under solvent-free conditions (Scheme 1).
RESULTS AND DISCUSSION
To find the most effective 1,1-diacetylation, benzaldehyde was chosen as a
model substrate. It was treated with 2 equiv. of acetic anhydride in the presence
of 1.0 mmol of CoBr2 in different dry solvents at room temperature (Table 1).
Table 1. 1,1-Diacetylation of benzaldehyde with acetic anhydride in the presence of cobalt(II) bromide at
room temperature with different solvents
Entry
CoBr2 (mmol)
Solvent
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
9
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.1
THF
40
40
40
40
40
40
30
20
20
67
86
CH2Cl2
CHCl3
Et2O
76
80
EtOAc
DMF
CH3CN
—
78
82
88
98b
98b
—
aIsolated yield.
bThe solvent-free reaction is more effective.

444
G. A. MESHRAM AND V. D. PATIL
The reaction in tetrahydrofuran (THF), CH2Cl2, CHCI3, Et2O, EtOAc, dimethylfor-
mamide (DMF), and CH3CN (Table 1, entries 1–7) were less effective. Therefore, we
carried out the reaction under solvent-free conditions with excellent yield (98%,
entries 8 and 9).
The catalytic activity of CoBr2 for the 1,1-diacetylation of benzaldehyde
(2 mmol) with acetic anhydride (2 mmol) under room temperature was studied,
and it was found that the application of less than 0.1 mmol of cobalt(II) bromide
(22 mg) gave a moderate yield of the corresponding 1,1-diacetylation (Table 2,
entries 1 and 2), whereas the use of more than 0.1 mmol gave excellent yield
(Table 2, entries 3–5).
A variety of aromatic, aliphatic, and heterocyclic aldehydes were converted to
corresponding 1,1-diacetates using acetic anhydride in the presence of anhydrous
cobalt(II) bromide in excellent yields at room temperature and in short reaction
times. The results are summarized in Table 3. All aromatic aldehydes carrying
electron-donating or electron-withdrawing substituents reacted well and gave excel-
lent yields (Table 3, entries 1–14). Aliphatics and a,b-unsaturated aldehydes
produced acylals in good yields (Table 3, entries 16–19). Furfural was converted
to its 1,1-diacetate in moderate yield (Table 3, entry 15). 4-(N,N-Dimethylamineo)
benzaldehyde gave less yield under the same condition, which may be due to electron
donation by the dimethylamino group (Table 3, entry 25). We also studied the
aldehydes that have phenolic OH and carbonyl aldehyde groups under the same
condition. We observed that both carbonyl and phenolic OH groups were acylated
with similar yields (Table 3, entries 20–23). This reaction was further extended to
aromatic compounds that have two aldehyde groups, which were also acylated with
similar yield (Table 3, entry 24).
To evaluate the selectivity of this method, we investigated competitive
reactions for aldehydes in the presence of ketones using anhydrous cobalt(II)
bromide as catalyst under solvent-free conditions. While employing this catalytic
system, the highly selective conversion of aldehydes in the presence of ketones was
observed (Table 4, entries 1 and 2). We also compared the acetylation of 4-nitro ben-
zaldehyde with that of benzaldehyde and 4-methoxy benzaldehyde. These reactions
proceeded with high selectivity in the presence of this catalyst, showing the impor-
tance of electronic effects upon these reactions in the presence of this catalyst
(Table 3, entries 3 and 4). We also studied the acylation of 4-nitrobenzaldehyde in
the presence of 3-phenyl propionaldehyde under the same conditions. As shown in
Table 2. Catalytic effect of CoBr2 for the 1,1-diacetylation in the presence of cobalt(II) bromide at room
temperature without solvent
Entry
CoBr2 [mmol (mg)]
Time (min)
Yield (%)a
1
2
3
4
5
0.01 (2)
20
20
20
20
20
60
70
93
93
93
0.05 (11)
0.10 (22)
0.15 (33)
0.20 (44)
aIsolated yield of the corresponding sulfonylated product.

1,1-DIACETATES FROM ALDEHYDES
445
Table 3. CoBr2-catalyzed 1,1-diacetylation of benzaldehyde
Time
(min)
Yielda
(%)
Substrates (a)
Products (b)
1
2
20
15
93
94
3
4
5
6
15
15
25
25
97
96
94
93
7
8
25
25
86
90
9
15
30
95
93
10
(Continued )

446
G. A. MESHRAM AND V. D. PATIL
Table 3. Continued
Time
(min)
Yielda
(%)
Substrates (a)
Products (b)
11
12
25
25
90
82
13
30
80
14
15
30
30
80
70
16
17
18
25
25
25
92
90
90
19
20
25
25
96
93
21
30
87
22
23
30
25
90
92
(Continued )

1,1-DIACETATES FROM ALDEHYDES
447
Table 3. Continued
Time
(min)
Yielda
(%)
Substrates (a)
Products (b)
24
25
20
95
40
120
aYields refer to pure products, and all products were characterized by comparison of their infrared (IR)
and 1H NMR spectra.
Table 4. Chemoselective synthesis of acylals from aldehydes using acetic anhydride in the presence of
anhydrous CoBr2 at room temperature
Entry
Reaction
1
2
3
4
5

448
G. A. MESHRAM AND V. D. PATIL
Table 4 (entry 5), the rate of acylal formation of 3-phenyl propionaldehyde is less
than 4-nitrobenzaldehyde, which may be due to enol formation of 3-phenyl propio-
naldehyde in the presence of this catalyst.
CONCLUSIONS
In conclusion, this article describes a method in which anhydrous cobalt(II)
bromide (CoBr2) is used as a highly efficient catalyst for the diacetylation of
aldehydes. The advantages include the low cost, ease of catalyst handling, require-
ment of very small amount of catalyst (0.1 mol%, 22 mg) and Ac2O, mild reaction
conditions (room temperature), excellent yield, short reaction time, and no undesir-
able side products. The solvent-free conditions employed in the present method
should make it environmentally friendly and useful for industrial applications.
EXPERIMENTAL
Typical Procedure
A mixture of aliphatic, aromatic, and heterocyclic aldehydes (2 mmol), 5 mmol
acetic anhydride (Ac2O), and 0.1 mol% (22 mg) anhydrous cobalt(II) bromide
(CoBr2) was stirred magnetically at room temperature, and the progress of the
reaction was monitored by thin-layer chromatography (TLC). The reaction mixture
was diluted with water (30 ml) and extracted with chloroform (3 ꢁ 30 ml). The com-
bined chloroform extracts were washed successively with 10% sodium bicarbonate
and water, dried with Na2SO4, and concentrated under reduced pressure. In all the
cases, the product obtained after the usual workup gave satisfactory spectral data.
Characterization Data for Products
1,1-Diacetoxy-1-phenyl methane (1b). IR (KBr): 3040, 1760, 1588, 1517,
1
1456, 1372, 1239, 1203, 1061, 1010, 922, 846, 763, 699 cmꢂ1. H NMR (300 MHz,
CDCl3): d ¼ 7.7 (s, 1H), 7.34–7.51 (m, 5H), 2.1 (s, 6H).
1,1-Diacetoxy-1-(4-nitrophenyl) methane (4b). IR (KBr): 3087, 1763,
.
1610, 1529, 1350, 1231, 1203, 1062, 1013, 976, 856 cmꢂ1 1H NMR (300 MHz,
CDCl3): d ¼ 8.25 (d, J ¼ 8.2 Hz, 2H), 7.7 (d, J ¼ 8.2 Hz, 2H), 7.25 (s, 1H), 2.15
(s, 6H).
ACKNOWLEDGMENT
We thank the Faculty of Chemistry, University of Mumbai, India, for support-
ing this work.
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