Cupric sulfate pentahydrate: A mild and efficient catalyst for the chemoselective synthesis of 1,1-diacetates from aldehydes in a solvent-free system

Article abstract of DOI:10.1007/s00706-005-0499-0

Cupric sulfate pentahydrate was found to be an efficient catalyst for the protection of aldehydes as 1,1-diacetates in high yields in a solvent-free system at room temperature. Ketones are not affected under these reaction conditions. Springer-Verlag 2006.

Full text of DOI:10.1007/s00706-005-0499-0

Monatshefte f €u r Chemie 137, 1075–1078 (2006)
DOI 10.1007/s00706-005-0499-0
Cupric Sulfate Pentahydrate: A Mild
and Efficient Catalyst for the Chemoselective
Synthesis of 1,1-Diacetates from Aldehydes
in a Solvent-Free System
Ã
and Hossein A. Oskooie
Majid M. Heravi , Shima Taheri, Khadijeh Bakhtiari,
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
Received September 26, 2005; accepted (revised) October 29, 2005
Published online July 3, 2006 # Springer-Verlag 2006
Summary. Cupric sulfate pentahydrate was found to be an efficient catalyst for the protection of
aldehydes as 1,1-diacetates in high yields in a solvent-free system at room temperature. Ketones are not
affected under these reaction conditions.
Keywords. 1,1-Diacetates; CuSO Á5H O; Protection; Acylals; Aldehydes.
4
2
Introduction
The protection-deprotection reaction sequence constitutes an integral part of
organic synthesis such as the preparation of monomers, fine chemicals, and reac-
tion intermediates or precursors for pharmaceuticals. These reactions often involve
the use of acidic, basic, or hazardous reagents and toxic metal salts [1].
Acylals or 1,1-diacetates are synthetically useful as aldehyde protecting groups
[
2]. They are an alternative to acetals due to their stability in mildly acidic and
basic media and ease of chemoselective preparation in the presence of ketones [3].
In recent years, a number of different methods have been reported for the synthesis
of 1,1-diacetates and the regeneration of their parent aldehydes [4]. However, many
of these methods suffer from one or more drawbacks, such as long reaction times,
high catalyst to substrate ratio, use of volatile organic solvents, or large amounts of
solid supports, which eventually result in the generation of a large amount of toxic
waste, expensive reagents, unsatisfactory yields, and tedious work-up procedures.
Nevertheless, it is still desirable to develop alternative and milder conditions for the
preparation of acylals and to remove this protecting group.
à Corresponding author. E-mail: mmh1331@yahoo.com

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076
M. M. Heravi et al.
In recent years the use of inorganic reagents under solvent-free conditions has
rapidly increased, as these reactions often involve milder conditions, easier work-up,
and higher selectivity than similar reactions using organic reagents in solution [5, 6].
In continuation of our program to develop reactions in solvent-free systems
[
1
7–12], herein we report a simple and highly efficient process for the synthesis of
,1-diacetates.
Results and Discussion
Treatment of an aldehyde with acetic anhydride in the present of 10 mol% of
CuSO Á5H O in the absence of solvent at room temperature afforded the corre-
4
2
sponding geminal diacetate derivative in very high yields (Scheme 1).
The presence of electron donating and electron withdrawing groups on the
aromatic ring makes a difference to the reaction rates for the synthesis of 1,1-
diacetates. Substrates having electron-donating groups in the para position of
the aromatic ring underwent the reactions in a short period of time (Table 1, entries
4
(
and 5), whereas electron-withdrawing groups lead to higher reaction times
Table 1, entries 7–9).
It is noteworthy to mention that ketones such as acetophenone or benzophene-
none did not react under the same conditions (Table 1, entries 12 and 13). This
Scheme 1
Table 1. Synthesis of 1,1-diacetates using CuSO Á 5H O
4
2
mp
ꢀ
Time
min
Yielda
%
Entry
Substrate
C
found
reported
b
1
2
3
4
5
6
7
8
9
Isobutyraldehyde
Butyraldehyde
10
85
87
99
99
99
99
99
98
98
96
98
–
À
–
–
b
15
À
Benzaldehyde
15
43
80
63
81
89
65
125
86
53
–
44–45 [13]
81–82 [14]
64–65 [15]
81–82 [16]
90 [17]
4-Methylbenzaldehyde
4-Methoxybenzaldehyde
4-Chlorobenzaldehyde
2-Nitrobenzaldehye
3-Nitrobenzaldehye
4-Nitrobenzaldehye
Cinnamaldehyde
Furfuraldehyde
20
20
30
120
90
64–66 [15]
150
15
125–126 [15]
1
1
1
1
0
1
2
3
84–86 [13]
5
52–54 [18]
Acetophenone
No reaction
No reaction
–
–
Benzophenone
–
–
a
b
Yields refer to isolated pure products; oily products were obtained

Chemoselective Synthesis of 1,1-Diacetates
1077
Scheme 2
proved that a chemoselective protection of aldehydes in the presence of ketones
could be achieved with this procedure (Scheme 2).
In conclusion, we developed a convenient and efficient procedure for the synthesis
of acylals using catalytic amounts of CuSO Á5H O under mild reaction conditions
4
2
at room temperature. Some of the major advantages of this procedure are very good
yields, use of an inexpensive, nontoxic, readily available, and mild Lewis acid
catalyst, absence of volatile and hazardous solvents, and high chemoselectivity.
Experimental
Melting points were measured by using the capillary tube method with an electrothermal 9100
1
apparatus. H NMR spectra were recorded on a Bruker DRX-90 AVANCE spectrometer using TMS
as internal standard (CDCl solution). IR spectra were recorded from KBr disks on the FT-IR Bruker
3
Tensor 27. All products are known compounds and were identified by comparison of their spectra and
physical data with those of Refs. [13–18].
Preparation of Acylals, General Procedure
Cupric sulfate pentahydrate (10 mol%) was treated with 1 mmol aldehyde and 3 mmol acetic anhy-
dride. The slurry mixture was stirred for the indicated time (Table 1) at room temperature. The progress
of the reaction was monitored by TLC. After completion of the reaction, the catalyst was filtered off
3
3
and washed with 5 cm Et O. Then the filtrate was washed with 5 cm 5% NaHCO solution and
3
2
3
2
Â5 cm brine successively, and dried (MgSO ). The solvent was evaporated under reduced pressure.
4
The crude product was purified over silica gel by column chromatography to provide the pure product.
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