Bis(perfluorooctanesulfonyl)imide supported on fluorous silica gel: Application to protection of carbonyls

Article abstract of DOI:10.1016/j.jfluchem.2012.05.016

The immobilization of bis(perfluorooctanesulfonyl)imide (HNPf₂) on fluorous silica gel (FSG) and its utilization in protection of carbonyls have been investigated. This system is reasonably general and can be applied to converting several carbonyls to the corresponding acetals and ketals in good to excellent yields. There is no need for the use of anhydrous solvents or inert atmosphere. Recycling studies have shown that the FSG-supported HNPf₂ catalyst can be readily recovered and reused several times without significant loss of activity.

Full text of DOI:10.1016/j.jfluchem.2012.05.016

Journal of Fluorine Chemistry 140 (2012) 121–126
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Short Communication
Bis(perfluorooctanesulfonyl)imide supported on fluorous silica gel: Application to
protection of carbonyls
*
Mei Hong , Guomin Xiao
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, People’s Republic of China
A R T I C L E I N F O
A B S T R A C T
Article history:
The immobilization of bis(perfluorooctanesulfonyl)imide (HNPf2) on fluorous silica gel (FSG) and its
utilization in protection of carbonyls have been investigated. This system is reasonably general and can
be applied to converting several carbonyls to the corresponding acetals and ketals in good to excellent
yields. There is no need for the use of anhydrous solvents or inert atmosphere. Recycling studies have
shown that the FSG-supported HNPf2 catalyst can be readily recovered and reused several times without
significant loss of activity.
Received 20 March 2012
Received in revised form 15 May 2012
Accepted 15 May 2012
Available online 24 May 2012
Keywords:
ß 2012 Elsevier B.V. All rights reserved.
Fluorous silica gel
Bis(perfluorooctanesulfonyl)imide
Protection of carbonyls
1. Introduction
imidazolium–styrene copolymer-supported GaCl3 [17] have been
reported to be active for acetalization.
Protection of carbonyl groups plays an important role during
multistep syntheses in organic, medicinal, carbohydrate, and drug
design chemistry. Among carbonyl protecting procedures, acetali-
zation or ketalization is one of the most widely used methods for
aldehydes and ketones. The protection of carbonyl groups as acetals
is now commonly used as an important synthetic technique in the
course of preparation of many organic compounds [1,2]. In addition,
the acetals are important reactants for synthesis of enantiomerically
pure compounds, which are widely used as steroids, pharmaceu-
ticals, and fragrances [3–7]. Traditional methods [1] for the
formation of acetals and ketals involve condensation of an aldehyde
or ketone with an alcohol or diol using Brønsted or Lewis acid
catalysis with a Dean-Stark trap or a dehydrating agent to remove
water. Examples of these include dry HCl in alcoholic solvent [8],
(MeO)3CH/p-TsOH [9], (MeO)3CH/Sc(NTf2)3 [10], (EtO)3CH/Amber-
lyst-15 [11], (MeO)3CH/InCl3 in refluxing cyclohexane–MeOH (3:1)
[12] and In(OTf)3 [13]. Unfortunately, some of these methods lead to
a series of problems, such as product separation, catalyst recovery
and corrosion. One way toavoid theseproblemsistousesolid acidas
catalyst, which is insoluble in the reaction medium, providing for
facile separation by simple filtration. Some solid catalysts such
as sulfonic acid-functionalized FSM-16 mesoporous silica [14],
MCM-41 [15], ammonium triflate-functionalized silica [16] and
In recent decades, the catalytic application of metal bis(per-
fluorooctanesulfonyl)imides in FBS has undergone rapid growth
[18–20]. But perfluorinated solvents are expensive and environ-
mentally persistent. Nishikido et al. have already reported the
immobilization of fluorous Lewis acids using
b-cyclodextrin
epichlorohydrin copolymer as a support to catalyze Diels–Alder
and Mukaiyama-aldol reactions in water [21]. They also reported
that FSG-supported fluorous Lewis acids act as effective catalysts of
Baeyer–Villiger and Diels–Alder reactions in water [22]. FSG has
been generally used in solid–liquid extraction to separate fluorous
compounds from organic compounds as well as in HPLC [23–27].
Bannwarth et al. originally reported Suzuki-Miyaura and Sonoga-
shira coupling reactions catalyzed by fluorous-tagged palladium
complexes immobilized on FSG in 1,2-dimethoxyethane [28]. From
both economical and environmental point of views, the use of
nontoxic solvents and nonmetallic catalysts is very promising. In
this paper, we wish to introduce the immobilization of HNPf2 on
FSG and its utilization in protection of carbonyls.
2. Results and discussion
2.1. Characterization of the catalyst
Fig. 1 shows the IR spectra between 4500 and 500 cmÀ1 of FSG,
HNPf2 and FSG–HNPf2, respectively. The results reveal that the
supported catalyst possesses characteristic peaks of both support
and bis(perfluorooctanesulfonyl)imide.
* Corresponding author. Tel.: +86 2552090612; fax: +86 2552090612.
E-mail address: 101100685@seu.edu.cn (M. Hong).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.05.016

122
M. Hong, G. Xiao / Journal of Fluorine Chemistry 140 (2012) 121–126
100
90
80
70
60
50
40
30
a
a
c
b
b
0
100
200
300
400
500
600
Temperature / oC
4400 4000 3600 3200 2800 2400 2000 1600 1200 800
Wavenumber/cm-1
Fig. 3. Thermal analysis of samples: (a) TGA of the pure FSG; (b) TGA of FSG–HNPf2.
Fig. 1. FTIR spectra of: (a) the pure FSG; (b) HNPf2; (c) FSG–HNPf2.
From Fig. 2, it can be seen that FSG–HNPf2 presents obvious
chromatographic purification and proceed without the require-
ment for inert or anhydrous reaction conditions.
Lewis acid sites as well as Brønsted acid sites. The intensive band at
1540 cmÀ1 and weaker one at 1450 cmÀ1 are assigned to Brønsted
acid sites and Lewis acid sites, respectively. Another intensive band
at 1490 cmÀ1 is attributed to a combination signal associated with
both Lewis acid and Brønsted acid sites. For fluorous silica gel, no
significant signals are observed at 1540 cmÀ1 band indicating that
the pure fluorous silica gel offers very weak Brønsted acidity.
The TGA curve of FSG (Fig. 3(a)) shows a fairly flat line, which
indicates that the support is highly stable before 500 8C. There is
one main stage of weight loss for TGA of FSG–HNPf2 (Fig. 3(b))
between 350 and 500 8C, which corresponds to the decomposition
of HNPf2 from the FSG framework. It implies that the supported
catalyst cannot be treated above 350 8C.
For the beginning of this study, reactivities of FSG–HNPf2, HNPf2
and metal bis(perfluorooctanesulfonyl)imide complexes were
investigated in the acetalization of benzaldehyde with trimethyl
orthoformate in methanol. FSG–HNPf2 catalyzed the reaction to give
benzaldehyde dimethyl acetal in the highest conversion of >99%
(Table 1, entry 5). The reaction catalyzed by HNPf2 without support
gave moderate yield (Table 1, entry 6), and the reaction in the
presence of FSG without HNPf2 gave low yield (Table 1, entry 7).
We next undertook examination of the conversion of a series of
aldehydes and ketones to the corresponding dimethyl acetals and
ketals using FSG–HNPf2. Acyclic acetals have frequently been paid
to special attention, owing to their liability as compared with cyclic
O,O-acetals. The reaction was carried out by stirring the carbonyl
compounds and trimethyl orthofomate (2 equiv.) in methanol with
1 mol% of FSG–HNPf2. While acetal formation was observed in the
presence of the catalyst and trialkyl orthoformate alone, the
addition of the alcohol accelerated the rate of the reaction. When
the reaction was attempted using the catalyst and alcohol alone
(no trialkyl orthoformate), significant acetal formation was not
observed. A wide variety of aldehydes and ketones underwent
smooth reaction to give the corresponding acetals and ketals in
good yield (Table 2). Aromatic aldehydes, such as p-chloroben-
zaldehyde, p-bromobenzaldehyde, p-nitrobenzaldehyde and
p-methoxybenzaldehyde could be acetalized to afford the corre-
sponding dimethyl acetals in excellent yields. The electronic
nature or position of the substituents on the aromatic ring showed
no effect on the conversion. Acid-sensitive substrate such as
2.2. Protection of carbonyls
We herein report effective protocols that facilitate the
protection of carbonyls as either their cyclic or acyclic acetals
and ketals using catalytic amounts of FSG–HNPf2 (Scheme 1). The
catalyst is very versatile and works well for the synthesis of
dimethyl acetals and ketals, diethyl acetals and ketals as well as
1,3-dioxolanes from a variety of aldehydes and ketones. The
reactions are extremely simple and do not generally require
a
Table 1
b
Comparison of catalytic activities in the acetalization of benzaldehyde with
trimethyl orthoformate.a
Entry
Catalyst
Conversion (%)b
1
2
3
4
5
6
7
8
FSG–Sn(NPf2)4
FSG–Hf(NPf2)4
FSG–Sc(NPf2)3
FSG–Yb(NPf2)3
FSG–HNPf2
HNPf2
68
79
89
87
>99
83
FSGc
34
None
Trace
1300
1400
1500
1600
Wavenumber/cm-1
1700
1800
1900
2000
a
Reaction conditions: 1 mmol benzaldehyde, 2 mmol trimethyl orthoformate,
3 mL methanol, 1 mol% catalyst, reflux, 2 h.
b
Detected by GC/MS. Conversion based on benzaldehyde.
c
Fig. 2. Pyridine-FTIR spectra of: (a) the pure FSG; (b) FSG–HNPf2.
The amount of the catalyst: 0.1 g.

M. Hong, G. Xiao / Journal of Fluorine Chemistry 140 (2012) 121–126
123
Scheme 1. Acetalization of carbonyl compounds catalyzed by FSG-supported bis(perfluorooctanesulfonyl)imide.
Table 2
Protection of carbonyls as dialkyl acetals (ketals).a
Entry
1
Aldehydes (ketones)
Time (h)
2
Conversion (%)b
Dimethyl acetals (ketals)
>99
Selectivity (%)
Dimethyl acetals (ketals)
100
Diethyl acetals (ketals)
97
Diethyl acetals (ketals)
100
100
100
2
3
2
2
93
98, 99, 97, 96c
100
100
>99
81
4
2
>99
79
100
100
5
6
7
8
9
2
2
3
2
2
94
93
91
99
81
80
100
100
100
100
100
100
100
100
100
100
>99
91
91
91
10
11
2
4
57
63
93
97
100
100
100
100
12
13
4
4
88
99
68
90
100
100
100
100
a
Reaction conditions: 1 mmol aldehyde or ketone, 2 mmol trialkyl orthofomate, 3 mL alcohol, 1 mol% FSG–HNPf2, reflux.
Detected by GC/MS. Conversion based on the carbonyls.
b
c
Catalyst was reused in three times. Loss of catalyst (<5%) during handling.

124
M. Hong, G. Xiao / Journal of Fluorine Chemistry 140 (2012) 121–126
furfural was efficiently protected as dimethyl acetal without any
accompanying self-condensation or ring cleavage (Table 2, entry
acetalization without any trace of by-products to give the
corresponding acetals in excellent yields. For reactions of some
less reactive ketones, such as cyclohexanone and acetophenone,
ketalization were also observed in excellent yields.
8). Notably,
a,b-unsaturated aldehyde was facilely acetalized
without concomitant double-bond isomerization (Table 2, entry 9).
Aliphatic aldehyde (Table 2, entry 10) reacted sluggishly, however,
the product yield was much lower than those obtained with
aromatic aldehydes. The ketalization reaction was also examined
over the FSG–HNPf2 system. A moderately hindered ketone,
acetophenone which is difficult to protect as its acetal is also
converted to the corresponding dimethyl acetal in 99% yield
(Table 2, entry 13).
A large number of methods exist for the synthesis of dimethyl
acetals, while fewer methods are available for the synthesis of
diethyl acetals [29,30]. We also examined the diethyl acetalization
of a variety of structurally different aldehydes and ketones (Table
2). Both activated and deactivated aldehydes underwent smooth
Cyclic acetals are also important protecting groups for carbonyl
compounds. The standard method for synthesis of 1,3-dioxolanes
consists of heating a mixture of the carbonyl compound and
ethylene glycol in refluxing benzene with the azeotropic removal
of water. This method is not particularly suitable for large-scale
synthesis and also uses the carcinogenic solvent benzene. We have
developed a practical method for the synthesis of 1,3-dioxolanes
(Table 3). In the method, toluene is used as a solvent and 1 mol%
FSG–HNPf2 serves as the catalyst. Under these conditions, at
110 8C, the reactions reached moderate to excellent conversion.
It is notable that o-hydroxybenzaldehyde did not form any trace
of dialkyl acetal and 1,3-dioxolane even after 24 h, mostly because
Table 3
Protection of carbonyls as 1,3-dioxolanes.a
Entry
1
Aldehydes (ketones)
Time (h)
2
Conversion (%)b
97, 98, 97, 97c
Selectivity (%)
100
2
3
2
2
>99
>99
100
100
4
5
6
7
8
2
2
3
2
2
93
100
100
100
100
100
>99
90
>99
71
9
2
5
72
88
100
100
10
11
12
5
5
>99
100
100
97
a
Reaction conditions: 1 mmol aldehyde or ketone, 2 mmol ethylene glycol, 3 mL toluene, 1 mol% FSG–HNPf2, reflux.
Detected by GC/MS. Conversion based on the starting carbonyls.
b
c
Catalyst was reused in three times. Loss of catalyst (<5%) during handling.

M. Hong, G. Xiao / Journal of Fluorine Chemistry 140 (2012) 121–126
125
o-hydroxybenzaldehyde has higher electron density around the
carbonyl carbon and it is less susceptible to nucleophilic attack by
alcohols.
The reaction mixture was heated at reflux for 2 h and then cooled
to room temperature. Supported catalyst was recovered by
filtration and washed with 1,2-dichloroethane (5 mL). FSG–HNPf2
was dried under vacuum for reuse in the next cycle. The reaction
mixture was analyzed by GC and GC/MS. The crude residue was
purified by column chromatography using silica gel with hexanes/
ethyl acetate (20:1 to 5:1 gradient) as the eluent system.
Spectroscopic data for selected examples are shown below.
2.3. Effect of the recovered FSG–HNPf2 on acetalization of carbonyls
The recycling performance of FSG–HNPf2 was also investigated
in the reactions of both p-chlorobenzaldehyde with triethyl
orthoformate in ethanol and benzaldehyde with ethylene glycol
in toluene. After the reaction, FSG–HNPf2 was recovered by simple
filtration. The data listed in Tables 2 and 3 showed recycling of the
catalyst was achieved by FSG–HNPf2 without obvious loss of
catalytic activities indicating the non-leaching behavior of acidic
contents from the catalyst during the course of reaction. The non-
leaching behavior of the acidic contents was also checked by doing
several blank experiments [31].
2-Phenyl-1,3-dioxolane: 1H NMR (500 MHz, CDCl3)
d 7.53–7.45
(m, 2H), 7.41–7.32 (m, 3H), 5.81 (s, 1H), 4.18–4.07 (m, 2H), 4.09–
3.97 (m, 2H). 13C NMR (125 MHz, CDCl3)
d 137.8, 129.3, 128.1,
126.3, 103.7, 65.5. MS m/z 150 (M+).
2-Methyl-2-phenyl-1,3-dioxolane: 1H NMR (500 MHz, CDCl3)
d
7.51–7.45 (m, 2H), 7.38–7.24 (m, 3H), 4.15–3.93 (m, 2H), 3.87–3.73
(m, 2H), 1.67 (s, 3H). 13C NMR (CDCl3)
d 143.1, 128.3, 127.6, 125.3,
108.7, 64.5, 27.6. MS m/z 164 (M+).
2-(4-Methoxyphenyl)-1,3-dioxolane: 1H NMR (500 MHz, CDCl3)
d
3. Experimental
7.43 (d, J = 8.5 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 5.78 (s, 1H), 4.17–
4.09 (m, 2H), 4.07–3.95 (m, 2H), 3.83 (s, 3H). 13C NMR (125 MHz,
3.1. General
CDCl3)
(M+).
d 160.5, 130.1, 127.6, 113.8, 103.9, 65.2, 55.3. MS m/z 180
Mass spectra were recorded on Saturn 2000 GC/MS instrument.
1H NMR and 13C NMR spectra were measured on Bruke Advance
RX500. The quantitative analysis of the reaction mixture was
determined by HP4890 GC analyzer with HP-5. FTIR and pyridine-
FTIR wereconductedona Bruker VERTEX70spectrophotometer. The
thermogravimetric analysis (TGA) was carried out on a Shimadazu
TGA-50 with a heating rate of 10 8C/min from 50 to 600 8C under
nitrogen atmosphere. Fluorous silica gel was purchased from
Fluorous Technologies Inc. All chemicals (AR grade) were commer-
cially available and used without further purification.
4. Conclusion
In conclusion, the present procedure using FSG–HNPf2 as a
catalyst provides a very simple, efficient and general methodology
for the protection of a variety of structurally diverse aldehydes and
ketones to the corresponding 1,3-dioxolanes and dialkyl acetals.
The significant advantages offered by this method are: (a) general
applicability to all types of carbonyl compounds providing 1,3-
dioxolanes as well as acetals, (b) high yields, (c) considerably lower
catalyst loading, (d) no migration of double bonds during
acetalization, (e) ease of handling, and (f) recyclability of the
catalyst. Thus, we believe that this procedure will provide a
practical and better alternative to the existing procedures for
acetalization.
3.2. Preparation of catalyst [22]
Into a solution of bis(perfluorooctanesulfonyl)imide (200 mg)
in ethanol (10 mL), fluorous silica gel (2 g) was added and the
resulting mixture was stirred for 1 h at room temperature. After
removal of the solvent under reduced pressure, residual FSG-
supported bis(perfluorooctanesulfonyl)imide was dried under
vacuum at 80 8C for 6 h.
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A solution of benzaldehyde (1 mmol) and trimethyl orthofor-
mate (2 mmol) in methanol (3 mL) was stirred as FSG–HNPf2
(1 mol%) was added. The reaction mixture was heated at reflux for
2 h and then cooled to room temperature. Supported catalyst was
recovered by filtration and washed with 1,2-dichloroethane (5 mL).
FSG–HNPf2 was dried under vacuum for reuse in the next cycle. The
reaction mixture was analyzed by GC and GC/MS. The crude residue
was purified by column chromatography using silica gel with
hexanes/ethyl acetate (20:1 to 5:1 gradient) as the eluent system.
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d 7.48 (d,
J = 7.6 Hz, 2H), 7.41–7.33 (m, 3H), 5.56 (s, 1H), 3.69–3.47 (m, 4H),
1.25 (t, J = 7.1 Hz, 6H). 13C NMR (125 MHz, CDCl3)
128.3, 126.7, 101.6, 61.5, 15.1. MS m/z 180 (M+).
d 139.5, 129.7,
(1,1-Dimethoxyethyl)benzene: 1H NMR (500 MHz, CDCl3)
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7.51–
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and toluene (3 mL) was stirred as FSG–HNPf2 (1 mol%) was added.

126
M. Hong, G. Xiao / Journal of Fluorine Chemistry 140 (2012) 121–126
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the fresh reactants were added to the filtrate (by assuming if the leaching of acidic
contents occur, it may lead to some conversion). However no conversion was
observed for the reactions indicating the non-leaching behavior of the acidic
contents.