Polymer-supported gadolinium triflate as a convenient and efficient Lewis acid catalyst for acetylation of alcohols and phenols

Article abstract of DOI:10.1016/j.tetlet.2008.03.005

A polymer-supported gadolinium triflate (CMPS-IM-Gd) catalyst was prepared from chloromethyl polystyrene (CMPS) resin using a simple and convenient procedure. This polymeric catalyst was used as an efficient Lewis acid catalyst for the acetylation of various alcohols and phenols with acetic anhydride, affording high yields under mild conditions. The reaction was completed in a short period of time with small amounts of the catalyst. The catalyst was reused over 10 times without any significant loss of its catalytic activity.

Full text of DOI:10.1016/j.tetlet.2008.03.005

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3165–3171
Polymer-supported gadolinium triflate as a convenient and
efficient Lewis acid catalyst for acetylation of alcohols and phenols
Hyo-Jin Yoon a, Sang-Myung Lee a, Jong-Ho Kim a, Hong-Jun Cho a,
Jung-Woo Choi a, Sang-Hyeup Lee b, Yoon-Sik Lee a,*
a School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea
b Department of Life Chemistry, Catholic University of Daegu, Gyeongsan 712-702, Republic of Korea
Received 18 December 2007; revised 27 February 2008; accepted 4 March 2008
Available online 6 March 2008
Abstract
A polymer-supported gadolinium triflate (CMPS-IM-Gd) catalyst was prepared from chloromethyl polystyrene (CMPS) resin using a
simple and convenient procedure. This polymeric catalyst was used as an efficient Lewis acid catalyst for the acetylation of various
alcohols and phenols with acetic anhydride, affording high yields under mild conditions. The reaction was completed in a short period
of time with small amounts of the catalyst. The catalyst was reused over 10 times without any significant loss of its catalytic activity.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Polymer-supported catalyst; Acetylation; Gadolinium triflate; Lewis acid catalyst
Functional group manipulations through protection and
deprotection strategies are highly essential in organic syn-
thesis and extensively used in the preparation of multifunc-
tional organic compounds. Among various protecting
methods, acetylation is one of the most frequently used
functional group transformations.1–3 The acetylation of
alcohols and phenols is typically performed using acetic
anhydride with the aid of either base or acid catalysts.
Some of the base catalysts are toxic, flammable and possess
offensive odours.4 Protic acids are also known to catalyze
the acetylation process.5 However, some of these catalysts
are not entirely satisfactory due to the instability of reac-
tants or products under the reaction conditions and the
time-consuming work-up procedures. In addition, several
Lewis acids, including simple metal salts,6 metal triflates7
and others,8 have been used as catalysts for these transfor-
mations. Although various acetylation methods are avail-
able, most of the aforementioned methods have one or
more drawbacks, which include long reaction times, harsh
reaction conditions and often, poor yields of the desired
products. Furthermore, most of the metal triflates are
rather expensive and some of them must be used under
critically anhydrous conditions for optimum results. Also,
most of the catalysts are usually used in environmentally
harmful organic solvents, thereby generating large
amounts of corrosive and toxic waste products. One of
the most promising solutions to this problem appears to
be the immobilization of the soluble catalysts onto an
insoluble matrix, without any reduction of catalytic perfor-
mance (activity and selectivity, etc.) with respect to the
homogeneous ones. Consequently, in recent years, some
of the supported acid catalysts have received much atten-
tion for their reusability, increasing reactivity, ease of
handling as well as for their environmental and economic
advantages.9 However, some of them still require high reac-
tion temperatures, tedious work and high preparation
costs.
Very recently, Gd(OTf)3 was used as a water-tolerant
Lewis acid in the aldol reaction10 as well as the acetylation
of alcohols and amines.11 It is not only more water-tolerant
*
Corresponding author. Tel.: +82 2 880 7080; fax: +82 2 876 9625.
E-mail address: biddory3@snu.ac.kr (Y.-S. Lee).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.005

3166
H.-J. Yoon et al. / Tetrahedron Letters 49 (2008) 3165–3171
than other lanthanide based metal triflates but also milder
and inexpensive. Previously, we have demonstrated the
advantages of various polymer-supported catalysts in
organic synthesis.12 In continuation of our ongoing studies
on polymer-supported catalysts, we found that immobi-
lized Gd(OTf)3 could be an effective Lewis acid catalyst.
Herein, we now report a polymer-supported gadolinium
triflate catalyst as a new, milder and efficient recyclable
heterogeneous catalyst for the acetylation of alcohols and
phenols (Scheme 1).
Our design for the preparation of polymer-supported
gadolinium triflate catalyst is depicted in Figure 1. The imi-
dazolium-loaded ionic liquid resin for the immobilization
of gadolinium triflate was synthesized from Merrifield resin
(CMPS, 1.80 mmol Cl/g) by treating with 1.5 equiv of
1-methylimidazole in DMF at 80 °C for 12 h. The loading
of imidazolium group was 1.42 mmol/g, which was deter-
mined by nitrogen analysis. The imidazolium-loaded ionic
liquid was then treated with potassium t-butoxide, which
acted as a base for the in situ deprotonation of imidazolium
salts. After washing out extra unreacted base, Gd(OTf)3
was then treated with CMPS-IM to give the desired poly-
mer-supported gadolinium triflate (CMPS-IM-Gd) cata-
lyst. The loading level of Gd was 0.05 mmol/g, which was
determined by inductively coupled plasma-atomic emission
spectrometry (ICP-AES). This means that 3.52% of the
imidazoium functionality on the resin participated in the
Gd complex formation. In addition, the gadolinium com-
plex formation was confirmed by energy dispersive X-ray
spectroscopy (EDX) and FT-IR spectroscopy. The surface
morphology of the catalyst was characterized by field emis-
sion scanning electron microscope (FE-SEM).13
As shown in Figure 2, the swelling volume of the CMPS-
IM-Gd catalyst was measured. The catalytic activity was
then evaluated using the acetylation of alcohols and phe-
nols as a model reaction. Since the solvent employed may
influence the catalytic activity of the CMPS-IM-Gd cata-
lyst, a variety of solvents were tested using benzylalcohol
as a model substrate (Table 1). As expected, the catalytic
activity of the CMPS-IM-Gd catalyst was well correlated
Polymer-supported
Gadolinium Triflate Catalyst (0.5 mol %)
Ac2O
(0.5 mmol) (1.5 mmol)
R-OAc
R-OH
+
DMSO, RT
Scheme 1.
Fig. 1. Preparation of the CMPS-IM-Gd catalyst.
Fig. 2. Swelling volume of the CMPS-IM-Gd catalyst. The swelling volumes of the polymer-supported gadolinium triflate in various solvents were
measured in a fritted column (ID 1 cm, length 15 cm). The resins (1.0 g) were swollen in a solvent at rt for 30 min, and then washed. The resin volume was
measured after filtering out the solvent.

H.-J. Yoon et al. / Tetrahedron Letters 49 (2008) 3165–3171
3167
Table 1
Effects of solvent on the acetylation of benzyl alcohol
O
CMPS-IM-Gd catalyst
(0.5 mol %)
O
O
OH
O
H3C
O
CH3
Various Solvents
RT
(0.5 mmol)
(1.5 mmol)
Rxn. time (h)
Conversiona (%)
Hexane
Toluene
Ether
MC
THF
CHCl3
Dioxane
MeCN
DMF
NMP
DMSO
2
3
a
78
91
38
58
78
77
24
42
41
66
23
43
32
52
50
75
90
>99
88
>99
>99
>99
Conversions were determined by GC/MS.
Table 2
Conversion of benzyl alcohol in the presence of the catalyst and in the absence of the catalyst
O
O
O
CMPS-IM-Gd catalyst
(0.5 mol %)
OH
(0.5 mmol)
Amount of catalyst (mol %)
O
H3C
O
CH3
DMSO (2 ml), RT
(1.5 mmol)
Entry
Conversiona (%) at a given reaction time
1 min
5 min
10 min
20 min
30 min
45 min
60 min
90 min
120 min
1
2
3
4
a
None
0.1
0.5
—
—
17
24
—
5
27
41
—
6
40
84
2
9
68
89
4
11
69
4
13
82
6
17
88
7
24
>99
>99
13
28
>99
>99
1.0
>99
>99
>99
Conversions were determined by GC/MS.
to the swelling property of the solvent employed. The
catalyst displayed the largest swelling volume and the high-
est activity in polar aprotic solvents such as DMF, NMP
and DMSO. As shown in Table 2, the amounts of catalyst
were also varied in order to monitor the progress of reac-
tion versus time. In the absence of catalyst, no appreciable
amount of the corresponding products was detected even
after prolonging the reaction time up to 24 h (entry 1).
By increasing the amount of the CMPS-IM-Gd catalyst,
the acetylation was shown to be greatly accelerated (entries
2–4). When 1.0 mol % of the catalyst was employed, the
reaction was completed in less than 30 min (entry 4) at
room temperature.
On the basis of these results, we next investigated the
scope of the substrate alcohols including phenols with
regard to the CMPS-IM-Gd catalyst-mediated acetylation,
and the results obtained are summarized in Table 3. To
examine the utility of this catalyst, a wide range of alcohols
including primary (acyclic, and benzylic), secondary (acy-
clic, cyclic and benzylic) and sterically hindered tertiary
alcohols were evaluated as substrates. The reactivity of
the substrate alcohol was greatly dependant on the steric
factor. Most of the primary and secondary alcohols were
easily converted to their corresponding acetate, with good
to excellent yields (entries 1–10). However, in the cases of
employing tertiary or sterically demanding alcohols, low
conversion was observed even after prolonging the reaction
time (entries 12–15, 18). When the reaction conditions such
as the amount of catalyst or the reaction temperature were
changed, the above-mentioned compounds were acetylated
in higher yields (entries 16–18). As shown in Table 4, a
series of phenols were also examined, and their conversions
to their acetyl products gave similar results under the same
conditions.
The stability of the catalyst and its reusability are the
main advantages of this polymeric catalyst. The CMPS-
IM-Gd catalyst could be stored and handled under open-
air conditions. Furthermore, the catalyst was quantita-
tively recovered by simple washing and filtration methods,
and proved to be reusable up to 10 times without any loss
of appreciable amount of catalytic activity (Table 5). In
most cases of employing different types of selected sub-
strates, the conversions at a given reaction time were
almost same as those obtained in the first use. The extent
of Gd ion leaching from the catalyst was very low as judged
by ICP-AES analysis. After the 2nd run to the 10th run, the
Gd contents in the recovered catalyst were remained
almost the same.
In conclusion, we have described an easy and novel
method for the immobilization of gadolinium triflate on a
polymer matrix. The resulting CMPS-IM-Gd catalyst was
found to be air-stable, non-volatile and much easier to
handle than its soluble counterpart, Gd(OTf)3. This com-
plex was evaluated as a heterogeneous catalyst for the acet-
ylation of alcohols and phenols with acetic anhydride, and
exhibited super activity over a wide range of substrates.

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H.-J. Yoon et al. / Tetrahedron Letters 49 (2008) 3165–3171
Table 3
Acetylation of various alcohols
CMPS-IM-Gd catalyst
(0.5 mol %)
Ac2O
(0.5 mmol) (1.5 mmol)
R-OH
R-OAc
+
DMSO (2 ml), RT
Entry
1
Alcohol
Acetate
Time
5 min
Yielda (%)
94
OH
OAc
O
O
2
3
5 min
1.5 h
94
OH
OH
OAc
OAc
>99
O
O
4
5
6
1 h
97
OAc
OAc
OH
OH
OH
S
S
1.5 h
1 h
>99
97
-O
-O
N+
N+
OAc
O
O
OH
OAc
7
8
5 h
96
HO
AcO
12 h
6 h
63
OH
OH
OAc
OAc
9
52
10
11
5 min
6 h
>99
93
OH
OAc
OH
OAc
12
13
14
24 h
24 h
24 h
14
17
18
OH
OAc
OH
OAc
OH
OAc
15
16
24 h
24 h
31
62b
OH
OAc

H.-J. Yoon et al. / Tetrahedron Letters 49 (2008) 3165–3171
3169
Table 3 (continued)
Entry
Alcohol
Acetate
Time
24 h
Yielda (%)
27d
OH
OAc
17
O
O
22 (38)c
OH
OAc
18
24 h
a
Yields were determined by GC/MS.
b
c
1 mol % of catalyst was used at room temperature.
3 mol % of catalyst was used at room temperature.
3 mol % of catalyst was used at 50 °C.
d
Table 4
Acetylation of various phenols
CMPS-IM-Gd catalyst
(0.5 mol %)
Ac2O
(0.5 mmol) (1.5 mmol)
R-OH
R-OAc
+
DMSO (2 ml), RT
Entry
1
Phenol
Acetate
Time
5 min
Yielda (%)
94
OH
OAc
2
3
3 min
3 min
92
91
I
OH
OH
I
OAc
Br
Br
Br
OAc
OAc
Br
OH
4
5
6
3 min
5 min
10 min
>99
93
Br
Br
O
O
O
O
OH
OAc
95
O
OH
O
OAc
7
45 min
97
OH
OAc
8
9
30 min
15 min
>99
91
OH
OH
OAc
OAc
10
5 min
99
OH
OAc
(continued on next page)

3170
H.-J. Yoon et al. / Tetrahedron Letters 49 (2008) 3165–3171
Table 4 (continued)
Entry
Phenol
Acetate
Time
5 min
Yielda (%)
93
O
O
11
12
OH
OAc
O
O
OH
OAc
1 h
96
95
OH
OH
OAc
OAc
13
5 min
a
Yields were determined by GC/MS.
Table 5
Recycling of the CMPS-IM-Gd catalyst
CMPS-IM-Gd catalyst
(0.5 mol %)
Ac2O
(0.5 mmol) (1.5 mmol)
R-OH
R-OAc
+
DMSO (2 ml), RT
Entry
Alcohols and phenols
Rxn. time
Conversiona,b (%)
1st
94
2nd
97
3rd
4th
5th
6th
7th
8th
9th
10th
>99
1
2
5 min
5 min
>99
>99
>99
>99
>99
>99
>99
OH
94
92
97
98
93
>99
93
96
94
94
96
94
>99
>99
>99
93
>99
91
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
98
OH
3
4
10 min
2 h
>99
>99
95
97
OH
OH
93
>99
97
90
5
5 h
96
92
>99
O
OH
a
Conversions were determined by GC/MS.
After the reaction, the mixture was filtered and washed with aq Na2CO3 solution, diethyl ether and brine. The catalyst was reused after drying.
b
Furthermore, the catalyst could be easily recovered by
simple washing and filtration and could be reused up to
10 times without significant loss in its catalytic activity.
These results suggest the increased potential of the
CMPS-IM-Gd catalyst to be used as a novel Lewis acid
catalyst in various organic reactions as well as industrial
applications. Studies involving the use of immobilized
gadolinium triflate catalyst in other Lewis acid-mediated
reactions are currently underway in our laboratory and will
be reported in due course.
the Korea Ministry of Commerce, Industry & Energy and
the ERC program of MOST/KOSEF(R11-2000-075-
03001-0).
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