Solid silica sulfuric acid (SSA) as a novel and efficient catalyst for acetylation of aldehydes and sugars

Article abstract of DOI:10.1016/j.tet.2006.06.038

Acetylation of aldehydes and sugars catalyzed by solid silica sulfuric acid (SSA) is described. In these reactions SSA shows a highly catalytic nature: easy to handle procedure, short reaction time, recycle exploitation, insensitivity to air and moisture, excellent isolated yields. The catalyst could be recycled at least five times.

Full text of DOI:10.1016/j.tet.2006.06.038

Tetrahedron 62 (2006) 7995–7998
Solid silica sulfuric acid (SSA) as a novel and efficient catalyst
for acetylation of aldehydes and sugars
a,b,*
a
Yang Shen, Li-yan Fan, Yu Wan and Da-qing Shi
c
a
a,b
Hui Wu,
a
Department of Chemistry, Xuzhou Normal University, Xuzhou 221116, PR China
Key Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Xuzhou 221116, PR China
b
c
Department of Chemistry, Tongji University, Shanghai 200092, PR China
Received 26 March 2006; revised 12 June 2006; accepted 13 June 2006
Available online 30 June 2006
Abstract—Acetylation of aldehydes and sugars catalyzed by solid silica sulfuric acid (SSA) is described. In these reactions SSA shows
a highly catalytic nature: easy to handle procedure, short reaction time, recycle exploitation, insensitivity to air and moisture, excellent
isolated yields. The catalyst could be recycled at least five times.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
corrosion, effluent pollution and non-recoverable catalysts
and use of toxic organic solvents. In order to overcome these
drawbacks, mild, quick, and environmentally friendly con-
ditions have been developed. There are so many solid
Protection of aldehydes is a frequently desired exercise in
organic synthesis as it is often necessary to carry out a
reaction on a multifunctional substrate without affecting
a carbonyl group. Previously, aldehydes are often protected
by acetalization through reaction between aldehydes and
alcohols or trimethyl orthoformate in the presence of
acid catalyst or others such as copper(II) tetrafluoroborate,
DDQ–EtOH, CAN–Na CO , etc. However, these methods
2
1
8
19
catalysts, such as b-zeolite, sulfated zirconia, montmoril-
1
20
21
lonite clays, expensive graphite, trimethylchlorosilane/
2
2
23
2ꢀ
sodium iodide, scandium triflate, TiO /SO4 solid
2
superacid, iodine, Bi(OTf) xH O, AlPW O , and
3 2 12 40
2
3
24
25
26
27
4
28
LiOTf.
5
6
3
have some drawbacks such as long reaction time, high
temperature, use of costly catalysts, use of additional
reagents, requirement of special effort for catalyst prepara-
tion, need to use special apparatus, moderate yields, and
side reactions. The most serious drawback is that these
methods have no global utility and most of the products
are liquid, which may contain impurities and are difficult
to be purified compared to the powder and crystal.
We herein disclose a new mild and efficient protocol
(Scheme 1) for diacetylation of aldehydes using AcO2
(3–20 equiv) catalyzed by 0.06 mol % of SSA in short time.
OSO3H
RCHO + Ac O
RCH(OAc)2
2
2
Neat, r.t. 50-70s
1
Scheme 1.
Thus, 1,1-diacetates are developed as new protecting groups
for aldehydes due to their stabilities, easy purification, and
Carbohydrates, which are central to a wide array of biologi-
cal processes, have received much attention. Based on
7
–11
29
easy conversion into parent aldehydes.
are obtained from aldehydes and acetic aldehyde using
Usually, they
the concept of protected and unprotected glycosylation
reagents, further extension to so-called ‘programmable’ syn-
theses need efficient synthesis of fast and convenient pro-
1
2
strong proton acids such as sulfuric acid, phosphoric
acid, methanesulfonic acid or Lewis acid as Nafion-H,
1
2
12
13
30
1
4
11
15
ZnCl , ferric chloride, phosphorus trichloride or
2
tected sugar building blocks for the synthesis of biologically
potent oligosaccharides, glycoconjugates, as well as natural
1
6
17
LiBr, H NSO H. These methods have not been entirely
2
3
3
1
satisfactory owing to such drawbacks as low yields (4% in
the case of 4-nitrobenzaldehyde ), long reaction time (up
to 120 h in the case of 2-furaldehyde ), problems of
products. Per-O-acetylation is a frequently used reaction
for protection of sugars and is often carried out using acetic
anhydride as reagent and a catalyst such as pyridine,
1
5
1
5
32
3
3
34
pyridine derivatives, sodium acetates. However, dealing
with large volumes of pyridine and other homogeneous cata-
lysts is troublesome and recovery of catalysts is also diffi-
Keywords: Silica sulfuric acid (SSA); Acetylation; Aldehydes; Sugars.
*
Corresponding author. Tel.: +86 0516 83500349; fax: +86 0516
3403164; e-mail: wuhui72@yahoo.com.cn
3
5
8
cult. A variety of other catalysts, iodine, strong inorganic
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.06.038

7996
H. Wu et al. / Tetrahedron 62 (2006) 7995–7998
3
6
37
38
acid, Lewis acid, anionic surfactants, montmorillonite
K10, Nafion-H, H-b zeolite, zirconyl sulfophenyl phos-
converted into the corresponding geminal diacetates even
when the reaction complexes were stirred for 24 h.
3
9
40
41
4
2
43
44
45
phonate, lipases, Cu(OTf)2, and Sc(OTf)3 have been
investigated.
The results in Table 2 indicate that in contrast to the conven-
tional 4, wherein an excessive amount of Ac O was needed
2
SSA is an excellent acidic catalyst, which was frequently
used to promote some important reaction.
and neutralization followed by tedious workup and purifica-
tion, our method employing stoichiometric amount of Ac O
4
6–48
But it is never
2
used to catalyze acetylation reactions. Herein, we report
a new mild and efficient protocol (Scheme 2) for acetylating
sugar with Ac O catalyzed by SSA at room temperature.
offers a chance to carry out the 4 under solvent-free condi-
tions. Disaccharides (entries 3f–3g) required longer reaction
time than pentoses and hexoses (entries 3a–3e) and the
amount of SSA for disaccharides was 0.06 mol %, while it
was 0.03 mol % for monosaccharides. The reaction terminal
could easily be monitored when the reaction system cooled to
room temperature automatically due to its heat liberation. It
could also be judged by TLC. The outstanding feature of
this method was that the catalyst could be easy recycled
five times without significant deactivation. A comparison
of this method with previous ones, in Table 3, clearly shows
the advantages of this method. The data in Table 3 also show
that some protocols took much longer time, some used no-
recovery catalyst, or some used dangerous materials with
reduced isolated yields. This protocol is so efficient in acety-
lation of 3-nitrobenzaldehyde in less than 0.8 min, while the
2
OSO3H
O
O
Ac2O
AcO
+
HO
Neat, r.t, 8-30min
OAc
OH
3
4
Scheme 2.
2
. Results and discussion
As shown in Table 1, a series of geminal diacetates 2 were
synthesized with the catalyst SSA at room temperature.
We found that both aromatic and aliphatic aldehydes gave
high yields (ꢁ80%) and the reaction time was shorter than
that of previous methods. The results indicated that the
nature of substituents on the aromatic ring had no effect on
the reaction, except 2-methoxybenzaldehyde, which gave
lower yield due to the steric hindrance effect. Ketones, for
example, acetophenone and cyclohexanone could not be
1
1
same transformation requires 0.5–12 h if FeCl , b-zeo-
3
1
8
28
lite, and LiOTf are used. The use of LiOTf is equally
effective for benzaldehyde, but reaction time is much longer
(14 h). Compared with K-10, which has shown no effect for
4-hydroxybenzaldehyde, the catalytic activity of SSA is
observed in 99% yield and in a very short time (70 s).
Table 1. SSA-catalyzed solvent-free acetylation of aldehydes with acetic anhydride
a,b
Yield (%)
ꢂ
Entry
Aldehyde
Ac
2
O (equiv)
Time (s)
Mp ( C) found
Reported
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
Butyraldehyde
Pentanal
Benzaldehyde
p-Nitrobenzaldehyde
m-Nitrobenzaldehyde
4-Chlorobenzaldehyde
2,4-Dichlorobenzaldehyde
4-Hydroxybenzaldehyde
p-Tolualdehyde
4-Cyanobenzaldehyde
4-Methoxybenzaldehyde
2-Bromobenzaldehyde
4-Bromobenzaldehyde
Salicylaldehyde
3
3
3
20
20
15
20
15
3
15
3
3
15
3
3
60
60
60
50
50
50
50
70
50
50
50
60
60
60
50
91
85
82
99
93
99
85
99
99
98
95
98
96
96
80
2
5
44–45
124–125
64–65
44–45
125–126
2
0
7
20
64–65
81–82
101–102
25
81–82
1
102–104
92–93
80–81
101–102
67–68
89–90
90–91
101–103
66–68
17
81–82
98–102
67–68
9
25
1
7
103–104
2-Methoxybenzaldehyde
a
Yield of pure isolated products.
Products characterized by H NMR spectroscopy and compared with authentic samples.
b
1
a
Table 2. SSA-catalyzed solvent-free per-O-acetylation of sugar with acetic anhydride
Entry
Sugar
Product
Ac
2
O (equiv)
Time (min)
20
10
10
20
8
25
25
30
a:b
1.7
20
2.1
4.2
14
1.9
1.1
20
Yield (%)
b
3
3
3
3
3
3
3
3
a
b
c
d
e
f
D-Glucose
D-Xylose
D-Glucopyranose pentaacetate
D-Xylopyranose tetraacetate
D-Galactopyranose pentaacetate
D-Mannopyranose pentaacetate
L-Rhamnopyranose tetraacetate
D-Lactose octaacetate
5.1
4.1
5.1
5.1
4.1
9.0
9.0
9.0
94
96
98
89
b
b
D-Galactose
D-Mannose
L-Rhamnose
D-Lactose
D-Maltose
Sucrose
b
b
90
91
c
c
g
h
D-Maltose octaacetate
Sucrose octaacetate
88
91
c
a
b
c
Yield of pure isolated products.
SSA 0.03 mol %.
SSA 0.06 mol %.

H. Wu et al. / Tetrahedron 62 (2006) 7995–7998
7997
Table 3. Comparison of protocols for acylation of aldehydes and sugars
work up procedure was separated. The residue was washed
ꢂ
with 95% EtOH and dried at 110 C for 12 h to give pure
SSA for further use.
Entry Substrate
Catalyst
T
Time Yield Ref.
(min) (%)
ꢂ
(
C)
a
3
1
a
D-Galactose
SSA
I
K-10
Cu(OTf)
Sc(OTf)
25
25
25
10 98
120 98
600 92
c
3.4.1. Spectral data of new products.
3.4.1.1. 4-Hydroxybenzaldehyde. Colorless crystal; H
2
35b
39
44
45
a
b
1
b
2
b
0/15 1500 90
25
NMR (400 MHz, CDCl ) d 7.67 (s, 1H), 7.54 (d, J¼8.4 Hz,
3
13
3
510 88
2
H), 7.13 (d, J¼8.4 Hz, 2H), 2.31 (s, 3H), 2.12 (s, 6H).
C
b
3-Nitrobenzaldehyde
SSA
FeCl
25
0
0.8
NMR (100 MHz, CDCl ) d 168.95, 168.42, 151.29, 132.79,
3
3
30 93
120 91
720 93
9
127.80, 121.54, 88.85, 20.83, 20.57. Anal. Calcd for
C H O : C, 58.64; H, 5.30. Found: C, 58.59; H, 5.41%.
e
b-Zeolite 60
25
18
28
a
b
1
3 14 6
LiOTf
1
1
c
4-Methoxybenzaldehyde SSA
25
25
0.8 95
1740 91
1
3
.4.1.2. 4-Bromobenzaldehyde. Colorless crystal; H
b
LiOTf
28
a
NMR (400 MHz, CDCl ) d 7.62 (s, 1H), 7.54 (d, J¼
3
d
4-Hydroxybenzaldehyde SSA d
K-10
25
25
1.2 99
13
8
.4 Hz, 2H), 7.39 (d, J¼8.0 Hz, 2H), 2.13 (s, 6H). C
NMR (100 MHz, CDCl ) d 168.38, 134.23, 131.54,
20
3
a
b
c
d
e
Present work.
128.14, 123.69, 88.85, 20.53. Anal. Calcd for C H BrO :
1
C, 46.02; H, 3.86. Found: C, 46.15; H, 3.96%.
1
11
4
Long reaction time.
No recovery of catalyst.
No reaction.
1
3.4.1.3. 2-Bromobenzaldehyde. Colorless crystal; H
Heat is needed.
NMR (400 MHz, CDCl ) d 7.93 (s, 1H), 7.62 (dd, J¼
3
8
1
.4 Hz, J¼1.2 Hz, 1H), 7.57 (dd, J¼8.4 Hz, J¼1.6 Hz,
In conclusion, SSA is a cheap, green, easily recycled, and
efficient catalyst for acetylation of aldehydes and sugar at
excellent yield. We believe that this method should be given
a wide application in protection of the hydroxyl and carboxy.
1
3
H), 7.30 (m, 2H), 2.13 (s, 6H). C NMR (100 MHz,
CDCl ) d 168.08, 134.58, 132.94, 130.78, 127.58, 127.32,
3
122.24, 88.77, 20.41. Anal. Calcd for C H BrO : C,
11 11 4
46.02; H, 3.86. Found: C, 46.11; H, 3.85%.
1
3
. Experimental
3.4.1.4. 2-Methoxybenzaldehyde. Colorless crystal; H
NMR (400 MHz, CDCl ) d 8.02 (s, 1H), 7.49 (d, J¼8.4 Hz,
3
3
.1. General
2H), 7.36 (t, J¼7.6 Hz, 1H), 7.00 (t, J¼7.6 Hz, 1H), 6.91 (d,
1
3
J¼8.4 Hz, 1H), 3.83 (s, 3H), 2.11 (s, 6H). C NMR
Melting points were measured with a Fisher–Johns melting
point apparatus without correction. The nuclear magnetic
resonance spectra were measured on a Bruker AM-400
(100 MHz, CDCl ) d 168.31, 156.71, 130.65, 128.68,
3
123.54, 120.19, 110.69, 85.38, 55.36, 20.60. Anal. Calcd
for C H O : C, 60.50; H, 5.92. Found: C, 60.54; H, 5.96%.
1
2 14 5
spectrometer with Me Si (TMS) as the internal reference
4
and CDCl as solvent.
3
1
3.4.1.5. Sucrose. Yellow oil; H NMR (400 MHz,
CDCl ) d 5.62 (d, J¼4 Hz, 1H), 5.35 (m, 3H), 5.01 (t,
3
3
.2. General procedure for acetylation of aldehydes
J¼9.6 Hz, 1H), 4.82 (d, J¼8 Hz, 1H), 2.11–1.95 (m, 26H).
1
3
C NMR (100 MHz, CDCl ) d 170.30, 170.11, 169.73,
3
Aldehyde(1 mmol), acetic anhydride (3–20 mmol), and SSA
0.06 mol %) were added in a flask and then stirred for about
min. The reaction was monitored by TLC. On completion
NaHCO3(aq) and CH Cl were added to the reaction system
169.69, 169.65, 169.52, 169.26, 169.14, 103.60, 89.52,
78.71, 77.22, 76.58, 75.30, 74.60, 69.84, 69.20, 68.07,
67.78, 63.23, 62.44, 61.37, 20.26, 20.23, 20.18, 20.15,
20.12, 20.10. Anal. Calcd for C H O : C, 50.29; H,
29 40 19
5.82. Found: C, 50.36; H, 5.91%.
(
1
2
2
yielding three layers: water on the top, silica sulfuric acid in
the middle, and CH Cl at the bottom. The bottom layer
2
2
was separated, washed with water and brine, dried over
anhydrous magnesium sulfate, and concentrated to crude
product and subjected to flash column chromatography.
Acknowledgements
We are grateful to the foundation of the ‘Natural Science
Research Project of University in Jiangsu Province’ (No.
JH03-038).
3
.3. General procedure for per-O-acetylation of sugar
To a mixture of sugar (2 mmol) and acetic anhydride (4.1–
mmol), SSA (0.03–0.06 mmol %) was added at room
9
temperature, and the reaction system was stirred until the
starting material disappeared completely (as monitored by
TLC).
References and notes
1. Arlette, S. C.; Guy, S. J. Org. Chem. 1979, 44, 4189.
2
3
4
. Greene, T. W. Protective Groups in Organic Synthesis, 3rd ed.;
Wiley: New York, NY, 1999.
. Rangam, G.; Jiaul, H.; Bhisma, K. P. J. Org. Chem. 2002, 67,
5842.
. Kumar, R.; Chakraborti, A. K. Tetrahedron Lett. 2005, 46,
The workup procedure was as described above.
3
.4. Preparation and recycle of SSA
The preparation of SSA was according to Mohammad Ali
Zolfigol. The middle layer in the first stage of the above
8319.
5. Karimi, B.; Ashtiani, A. M. Chem.Lett. 1999, 1199.
4
9

7998
H. Wu et al. / Tetrahedron 62 (2006) 7995–7998
6
. Nair, V.; Rajan, R.; Balagopal, L.; Nair, L. G.; Ros, S.; 30. (a) Ye, X. S.; Wong, C.-H. J. Org. Chem. 2000, 65, 2410; (b)
Mohanan, K. Indian J. Chem. 2005, 44B, 141.
. Cotelle, P.; Catteau, J. P. Tetrahedron Lett. 1992, 33, 3855.
. Jin, T. S.; Ma, Y. R.; Zhang, Z. H.; Li, T. S. Org. Prep. Proced.
Int. 1998, 30, 463.
. Kochhar, K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyaksha,
S. N.; Pinnick, H. W. J. Org. Chem. 1983, 48, 1765.
Reviewed in: Sears, P.; Wong, C.-H. Science 2001, 291, 2344.
31. (a) Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 1997, 52,
179; (b) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.;
Baasov, T.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734;
(c) Ye, X.-S.; Wong, C.-H. J. Org. Chem. 2000, 65, 2410.
32. Yu, B.; Xie, J.; Deng, S.; Hui, Y. J. Am. Chem. Soc. 1999, 121,
12196.
33. Hofle, G.; Steglich, W.; Vorbruggen, H. Angew. Chem., Int. Ed.
Engl. 1978, 17, 569.
34. Wolfrom, M. L.; Thompson, A. Methods Carbohydr. Chem.
1963, 2, 211.
35. (a) Kartha, K. P. R.; Field, R. A. Tetrahedron 1997, 53, 11753;
(b) Balaram, M.; Ravindranathan, K. P.; David, A. R.; Robert,
A. F. J. Org. Chem. 2004, 69, 7758.
36. (a) Hyatt, J. A.; Tindall, G. W. Heterocycles 1993, 35, 227;
(b) Binch, H.; Stangier, K.; Thiem, J. Carbohydr. Res. 1998,
306, 409.
37. (a) Limousin, C.; Cleophax, J.; Prtit, A.; Loupy, A.; Lukacs, G.
J. Carbohydr. Chem. 1997, 16, 327; (b) Dasgupta, F.; Singh,
P. P.; Srivastava, H. C. Carbohydr. Res. 1980, 80, 346.
38. Mueller, R.; Oftring, A. Anionic Surfactants as Catalysts for
Complete Acylation of Polyols; BASF: Germany, 1994.
39. Bhaskar, P. M.; Loganathan, D. Tetrahedron Lett. 1998, 39,
2215.
7
8
9
1
0. Jin, T. S.; Du, G. Y.; Li, T. S. Indian J. Chem., Sect. B 1998, 37,
39.
9
1
1. Perez, E. R.; Marrero, A. L.; Perez, R.; Autie, M. A. Tetra-
hedron Lett. 1995, 36, 1779.
2. Freeman, F.;Karcherski, E. M. J. Chem. Eng. Data1997, 22, 355.
3. Olah, G. A.; Mehrotra, A. K. Synthesis 1982, 962.
4. Sciabine, I. Bull. Soc. Chim. Fr. 1996, 1194.
5. Michie, J. K.; Miller, J. A. Synthesis 1981, 824.
6. Kumar, H. M. S.; Reddy, B. V. S.; Reddy, P. T.; Yadav, J. S.
J. Chem. Res., Synop. 2000, 86.
7. Jin, T. S.; Sun, G.; Li, Y. W.; Li, T. S. Green Chem. 2002, 4, 255.
8. Kumar, P.; Hegda, V. R.; Kumar, T. P. Tetrahedron Lett. 1995,
1
1
1
1
1
1
1
36, 601.
1
2
9. Raju, S. V. N. J. Chem. Res., Synop. 1996, 68.
0. Zhang, Z. H.; Li, T. S.; Fu, C. G. J. Chem. Res., Synop. 1997,
1
74.
1. Jin, T. S.; Du, G. Y.; Zhang, Z. H.; Li, T. S. Synth. Commun.
997, 27, 2261.
2
2
2
2
2
2
2
1
2. Deka, N.; Borah, R.; Kalita, D. J.; Sarma, J. C. J. Chem. Res.,
Synop. 1998, 94.
3. Aggarwal, V. K.; Fonguerna, S.; Vennall, G. P. Synlett 1998,
40. Kumareswaran, R.; Pachamuthu, K.; Vankar, Y. D. Synlett
2000, 1652.
41. Bhaskar, P. M.; Loganathan, D. Synlett 1999, 129.
42. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.; Rossi,
M. Synth. Commun. 2000, 30, 1319.
43. Junot, N.; Meslin, J. C.; Rabiller, C. Tetrahedron: Asymmetry
1995, 6, 1387.
44. Tai, C. A.; Kulkarni, S. S.; Hung, S. C. J. Org. Chem. 2003, 68,
8719.
382.
4. Jin, T. S.; Ma, Y. R.; Sun, X.; Liang, D.; Li, T. S. J. Chem. Res.
Synop. 2000, 96.
5. Nabajyoti, D.; Dipok, J. K.; Ruli, B.; Jadab, C. S. J. Org. Chem.
1997, 62, 1563.
6. Marc, D. C.; Kyle, J. E.; Matthew, C. O.; Ram, S. M. Tetra-
hedron Lett. 2001, 42, 8133.
7. Firouzabadi, H.; Iranpoor, N.; Nowrouzi, F.; Amani, K. Tetra-
hedron Lett. 2003, 44, 3951.
45. Lee, J. C.; An, C.; Hung, S. C. Tetrahedron Lett. 2002, 43, 851.
46. Peyman, S.; Minoo, D.; Mohammad, A. Z.; Mostafa, B. Tetra-
hedron Lett. 2005, 46, 7051.
2
2
8. Karimi, B.; Maleki, J. J. Org. Chem. 2003, 68, 4951.
9. (a) Varki, A. Glycobiology 1993, 3, 97; (b) Essentials of
Glycobiology; Varki, A., Cummings, R., Esko, J., Freeze, H.,
Hart, G., Marth, J., Eds.; Cold Spring Harbor Laboratory:
Cold Spring Harbor, NY, 1999.
47. Peyman, S.; Minoo, D.; Mohammad, A. Z.; Mostafa, B.
Tetrahedron Lett. 2003, 44, 2889.
48. Khodaei, M. M.; Khosropour, A. R.; Fattahpour, P. Tetrahedron
Lett. 2005, 46, 2105.
49. Zolfigol, M. A. Tetrahedron 2001, 57, 9509.