An efficient procedure for protection of carbonyls in Br?nsted acidic ionic liquid [Hmim]BF4

Article abstract of DOI:10.1016/j.tetlet.2004.04.138

Protection of carbonyls as acetals or ketals using Br?nsted acidic ionic liquid [Hmim]BF₄ as catalyst as well as solvent was investigated. Satisfactory results were obtained for the protection of carbonyls as cycloacetals or ketals with diols. The product can be separated conveniently from the reaction system, and the ionic liquid can be reused after removal of water.

Full text of DOI:10.1016/j.tetlet.2004.04.138

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4963–4965
An efficient procedure for protection of carbonyls
in Brønsted acidic ionic liquid [Hmim]BF4
Hai-Hong Wu, Fan Yang, Peng Cui, Jie Tang* and Ming-Yuan He
Center for the Chemistry of Ionic Liquids, Department of Chemistry, East China Normal University, Shanghai 200062, China
Received 8 January 2004; revised 10 April 2004; accepted 12 April 2004
Available online 13 May 2004
Abstract—Protection of carbonyls as acetals or ketals using Brønsted acidic ionic liquid [Hmim]BF4 as catalyst as well as solvent
was investigated. Satisfactory results were obtained for the protection of carbonyls as cycloacetals or ketals with diols. The product
can be separated conveniently from the reaction system, and the ionic liquid can be reused after removal of water.
Ó 2004 Elsevier Ltd. All rights reserved.
Protection of carbonyl groups plays an important role in
organic synthesis. Acid-catalyzed formation of acetals
and ketals is the most practical choice for protection of
aldehydes or ketones.1;2 The shortcomings of methods
currently used are: use of a large excess amount of
alcohols, poor chemical selectivity, and tedious work-up
processes. Alternative catalysts, including organome-
tallic reagents,3 silyl reagents,4 and inorganic com-
pounds (FeCl3, TiCl4, Bi(NO3)3),5 have recently been
reported for the protection of carbonyls as acetals or
ketals, and the search for a new catalyst is still being
actively pursued due to problems such as difficulty in
handling the reagents and limited examples.6
HO
R
R
O
HO
[Hmim]BF4
O
O
R'
R
R'
R
O
OMe
MeOH
[Hmim]BF4
R'
R'
OMe
Scheme 1.
([Hmim]BF4).8 We further report here a practical pro-
cedure for protection of various carbonyl compounds by
the formation of acetals or ketals in [Hmim]BF4 as
depicted in Scheme 1.
In recent years, ionic liquids have attracted intensive
interests as a possible replacement of traditional solvents
for organic reactions, particularly in the area of green
chemistry, due to their advantageous properties,
including negligible vapor pressure and high thermal
and chemical stability.7 An ever-increasing interest has
focused on ionic liquids as media for catalytic reactions
where the catalyst is in one phase and the product in
another, which makes product-isolation easy and cata-
lyst-reuse convenient. We have recently reported a
practical and efficient procedure for esterification of
carboxylic acids with alcohols in Brønsted acidic
ionic liquid, N-methylimidazolium tetrafluoroborate
In the protection of a variety of aldehydes and ketones
with neopentyl glycol, ethylene glycol or methanol,
Brønsted acidic ionic liquid [Hmim]BF4 acted as catalyst
as well as medium. Various carbonyls have been inves-
tigated and the results are summarized in Table 1.
The results in Table 1 clearly demonstrate that the
method of protecting carbonyls with neopentyl glycol is
efficient, with almost quantitative conversions and
selectivities in most cases. The molar ratio of aldehyde
or ketone to neopentyl glycol is 1:1. n-Hexanal was
converted in 3 h with 98% conversion and 100% selec-
tivity (Table 1, entry 1). Aromatic aldehydes, such as
benzaldehyde and o-nitrobenzaldehyde, also gave
satisfactory results with 93% and 100% conversions
(Table 1, entries 5 and 6). The protection of ketones was
also investigated. Cyclohexanone and cyclopentanone
were converted into the corresponding ketal with high
Keywords: Protection; Ionic liquid; Carbonyls.
* Corresponding author. Fax: +86-21-62232100; e-mail: jtang@chem.
ecnu.edu.cn
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.138

4964
H.-H. Wu et al. / Tetrahedron Letters 45 (2004) 4963–4965
a
Table 1. Results of protection for different aldehydes and ketones with alcohols in ionic liquid [Hmim]BF4
Run
Aldehydes (ketones)
Alcohols
Molar ratio
Conv.b (%)
Select.b;c (%)
T (°C)
Time (h)
1
n-Hexanal
Butanone
Neopentyl glycol
Neopentyl glycol
Neopentyl glycol
Neopentyl glycol
Neopentyl glycol
Neopentyl glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
Methanol
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:2
1:2
1:2
1:2
1:2
1:6
1:10
98
100
93
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
90
90
90
90
90
90
90
90
90
90
90
90
90
90
65
65
3
3.5
6
6
6
6
6
6
3
3
6
6
6
6
3
3
2
3
Cyclohexanone
Cyclopentanone
Benzaldehyde
o-Nitrobenzaldehyde
n-Hexanal
4
76
93
5
6
100
97
7
8
Butanone
94
92
9
Cyclohexanone
Cyclopentanone
Benzaldehyde
o-Nitrobenzaldehyde
p-Nitrobenzaldehyde
p-Chlorobenzaldehyde
n-Hexanal
10
11
12
13
14
15
16
100
60
100
100
53
100
50
Cyclohexanone
Methanol
a Ketones or aldehydes (27 mmol), alcohols (27 mmol), [Hmim]BF4 (4 mL).
b Detected by GC–MS. Conversions based on the starting carbonyls.
c Condensation by-products were detected.
a
Table 2. Recycling of [Hmim]BF4
selectivity (Table 1, entries 3 and 4). However, the
conversion of cyclopentanone was difficult.
Run
Conversion (%)
Selectivity (%)
1
2
3
4
5
6
7
8
92
92
94
94
95
94
95
94
100
100
100
100
100
100
100
100
When ethylene glycol was used, reaction rates slightly
decreased for straight chain carbonyls (Table 1, entries
7–14) under identical reaction conditions. For n-hexa-
nal, the reaction time required for similar conversions
and selectivities was longer than when neopentyl glycol
was used (Table 1, entry 7). Similarly, butanone reached
94% conversion after 6 h (Table 1, entry 8). However,
treatment of cyclopentanone with 2 equiv of ethylene
glycol gave quantitative conversion and selectivity (Ta-
ble 1, entry 10). The conversion of o-nitrobenzaldehyde
and p-nitrobenzaldehyde into corresponding protected
compounds produced higher yields than that of benz-
aldehyde (Table 1, entries 11–13). This is consistent with
reports that showed electron-withdrawing substituents
enhanced the rate of acetal formation.9
a Reaction of cyclohexanone with ethylene glycol (molar ratio 1:1) at
90 °C for 3 h.
In conclusion, aldehydes or ketones were efficiently
converted to corresponding acetals or ketals using
Brønsted acidic ionic liquid [Hmim]BF4 as catalyst as
well as medium. The products can be separated conve-
niently from the reaction system, and the ionic liquid
can be reused after removal of water. The merit of this
methodology is that it is simple, mild, and efficient.10
Further studies on its applicability are currently under
investigation.
The protection of n-hexanal and cyclohexanone with
methanol was also examined (Table 1, entries 15 and
16). n-Hexanal can be protected smoothly using a higher
proportion of methanol (molar ratio 1:6), while ketone
gave only about 50% conversion even when the molar
ratio of methanol was increased to 1:10. In this case,
large amount of excess methanol partially acted as the
solvent, and [Hmim]BF4 mainly played the role of an
acidic catalyst.
Acknowledgements
This project was supported by the National Natu-
ral Science Foundation of China (No. 20172016),
Shanghai Phosphor Project of Science and Technology
for Excellent Young Research (No. 01QA14017).
There was no need to remove the water produced during
the reaction, because [Hmim]BF4 was miscible with
water while the acetals and ketals were immiscible with
[Hmim]BF4. Therefore, the products could be separated
conveniently by decanting. The ionic liquid [Hmim]BF4
could be easily recycled. After the reaction, [Hmim]BF4
was readily separated and reused upon drying in
vacuum. The [Hmim]BF4 was reused eight times in
the protection of cyclohexanone with ethylene glycol,
each time with the same conversion and selectivity
(Table 2).
References and notes
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1991, pp 188–191; (b) Kocienski, P. J. Protecting Groups.
Thieme 1994, 156–170.

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4965
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10. General procedure for the protection of carbonyl groups:
The ionic liquid [Hmim]BF4 (4 mL) was mixed with n-
pentanal (2.9 mL, 27 mmol) and ethylene glycol (1.5 mL,
27 mmol). The mixture was heated in oil bath at designed
temperature. After the reaction, the organic layer was
separated from the ionic liquid by decanting, and the
product was detected by GC–MS. The ionic liquid
[Hmim]BF4 was reused after removal of water under
vacuum.