Selective acetolysis of primary benzyl groups in carbohydrate derivatives under the mild reaction condition

Article abstract of DOI:10.1016/j.carres.2019.107830

Selective acetolysis of the primary benzyloxy groups in a wide variety of carbohydrate derivatives was achieved in excellent yield using acetic anhydride and perchloric acid supported over silica (HClO₄–SiO₂) as a solid acid catalyst

Full text of DOI:10.1016/j.carres.2019.107830

Journal Pre-proof
Selective acetolysis of primary benzyl groups in carbohydrate derivatives under the
mild reaction condition
Monalisa Kundu, Anup Kumar Misra
PII:
S0008-6215(19)30448-3
DOI:
https://doi.org/10.1016/j.carres.2019.107830
CAR 107830
Reference:
To appear in: Carbohydrate Research
Received Date: 30 July 2019
Revised Date: 26 September 2019
Accepted Date: 2 October 2019
Please cite this article as: M. Kundu, A.K. Misra, Selective acetolysis of primary benzyl groups in
carbohydrate derivatives under the mild reaction condition, Carbohydrate Research (2019), doi: https://
doi.org/10.1016/j.carres.2019.107830.
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Graphical abstract
Selective acetolysis of primary benzyl groups in
carbohydrate derivatives under the mild reaction
condition
Monalisa Kundu and Anup Kumar Misra*
OBn
O
OAc
O
Ac2O/ HClO4-SiO2
R2O
R2O
OR1
OR1
o
0 C - RT, 10-15 min
R1 = alkyl, aryl
R2 = protecting group
74-90%

Selective acetolysis of primary benzyl groups in carbohydrate derivatives
under the mild reaction condition
Monalisa Kundu and Anup Kumar Misra*
Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata-
700054, India; E-mail: akmisra69@gmail.com
Abstract: Selective acetolysis of the primary benzyloxy groups in a wide variety of
carbohydrate derivatives was achieved in excellent yield using acetic anhydride and
perchloric acid supported over silica (HClO4-SiO2) as a solid acid catalyst in a fast reaction
condition without using any organic solvent. The reaction condition is significantly rapid and
can be scaled up for its use in the multi-step oligosaccharide synthesis.
Keywords: Carbohydrates; acetylation; acetolysis; benzyl; protecting groups; HClO4-SiO2.
1.
Introduction
Due to their biological significance, synthesis of complex oligosaccharides is an important
area of research,1,2 which requires a wide range of monosaccharide intermediates having
persistent and temporary protecting groups.3,4 Judicious selection of functional groups for
derivatization of monosaccharides plays decisive roles in the stereoselective glycosylations.5,6
Among several protecting groups used in the functionalization of carbohydrates, benzyl ether
is widely used because of the ease of its installation and removal. Although, benzyl ether
protecting group is considered as a stable protecting group, sometimes it is required to
convert it into other functional groups. Acetolysis7,8 is one of the age-old techniques for the
hydrolysis of glycosidic bonds as well as selective transformation of benzyl ethers into
acetoxy groups providing late stage functionalization of monosaccharides. Because of its
application in the synthesis of oligosaccharides, a number of reports appeared in the literature
on the development of suitable reaction conditions for the selective acetolysis of benzyloxy
groups. The commonly used reaction conditions require the treatment of benzylated
monosaccharide derivatives with an excess amount of strong protic or Lewis acids such as
H2SO4,9 TFA,10 p-TsOH,11 FeCl3,12 ZnCl2,13 ZnI2,14 BF3 OEt2,15 TMSOTf16 together with
acetic anhydride. Besides using the acidic catalysts few other reaction conditions have also
18
been reported using iodine,17 a combination of Et3SiH/I2 and Selectfluor.19 Despite their

wide applications most of the earlier reported reaction conditions suffer from several
shortcomings such as, use of harsh reaction condition, requirement of excess reagents, use of
corrosive and moisture sensitive reagents, longer reaction time, formation of by-products, low
yields etc. Since all the earlier reported reaction conditions are homogeneous nature, rigorous
workup of the reaction mixture is required for quenching the reaction. In this context, the
application of an efficient insoluble solid acid catalyst for the regioselective acetolysis of
benzyl ethers would be highly beneficial avoiding the use of stoichiometric quantity of
catalysts and workup procedures. In an ongoing program, treatment 6-O-benzylated
monosaccharide derivatives with H2SO4 or p-TsOH together with acetic anhydride did not
furnish selective 6-O-acetylated product instead a mixture products were obtained as a result
of non-selective acetolysis. In order to overcome this situation, it was envisioned that
catalytic amount of perchloric acid supported over silica (HClO4-SiO2) could act as a solid
acid catalyst in the presence of acetic anhydride for the selective acetolysis of 6-O-benzylated
20-22
monosaccharide derivatives. Chakraborti and co-workers
reported the preparation of
HClO4-SiO2 and demonstrated its catalytic potential in several organic transformations. Later,
many researchers have applied HClO4-SiO2 as an efficient solid acid catalyst23-28 alternative
to the commonly used protic or Lewis acid catalysts. Inspired by the catalytic potential of
HClO4-SiO2 it was decided to carry out selective acetolysis of 6-O-benzylated
monosaccharide intermediates under a mild reaction condition and reported herein. It is worth
mentioning that this method will be useful as alternative to the use of bulky protecting groups
such as TBDPS, TBDMS, trityl etc. at the primary position for selective removal and thus
support the atom economy in protecting group manipulations.
OBn
Ac2O
HClO4-SiO2
OAc
O
O
R2O
R2O
OR1
R1 = alkyl, aryl
R2 = protecting group
OR1
Scheme 1: Selective acetolysis of primary benzyloxy group of carbohydrate derivatives using
acetic anhydride in the presence of HClO4-SiO2.
2.
Results and discussion
In a set of initial experiments, p-methoxyphenyl 4-O-acetyl-2,3,6-tri-O-benzyl-β-
D
-
galactopyranoside (1) was treated with a varied quantity of acetic anhydride (1.0-2.0 equiv.)
and HClO4-SiO2 in different temperatures without using any solvent. It was observed that use

of 1.5 equiv. of acetic anhydride and HClO4-SiO2 (10 mg/100 mg of substrate) at 0 °C under
solvent-free condition furnished 85% yield of compound 19 in 10 min. without formation of
any by products. Increasing the quantity of the reagent and catalyst did not give significantly
improved yield of the product. Carrying out the reaction at room temperature proceeded with
the formation of by products (Table 1). After completion of the reaction it was filtered and
concentrated under reduced pressure without the requirement of any special workup. A
variety of 6-O-benzylated carbohydrate derivatives were transformed into 6-O-acetylated
products in excellent yields under the optimized reaction condition of the regioselective
acetolysis of the primary benzyloxy groups (Table 2). In some cases the reaction was carried
out at room temperature due to the extra stability of the 6-O-benzyl group. However, per-O-
benzylated methyl -mannoside (7) was found very reactive at 0 °C and produced significant
D
quantity of anomeric acetolysis product, which was controlled by carrying out the reaction at
−15 °C. The reaction condition is applicable in disaccharide derivative also to give
satisfactory yield (75%) without affecting the inter-glycosidic linkage and isopropylidene
ketal as observed in the case of compound 18. Several commonly used functional groups
such as acetyl, benzoyl, allyl, p-methoxyphenyl (PMP), azido, octyl, 2-trimethylsilylethyl
(TMSET), N-benzyloxycarbonyl (Cbz) and secondary benzyloxy groups as well as
isopropylidene group were found unaffected under the reaction conditions. As expected, the
other acid sensitive protecting group such as p-methoxybenzyl (PMB) group present in
compound 13 was also transformed into acetate under the reaction condition. Isomerization
of the anomeric protecting groups was not observed under the reaction condition, which was
witnessed in many acid catalyzed reactions. The reaction is significantly fast to furnish the
required products in very short interval of time in comparison to the other reported methods.
It is noteworthy that the reaction condition does not require any organic solvent and very less
quantity of catalyst was required for the completion of the reaction in contrast to the
requirement of stoichiometric quantity of acidic catalyst reported earlier, which may be due
to the increased surface area of the HClO4 due to the impregnation over SiO2. It is also
worthy to mention that allowance of the reaction for a longer reaction time led to the
formation of by-products, which might be due to the acetolysis of secondary benzyl or other
protecting groups present in the substrate resulting a decrease in over all yield of the expected
product. The catalyst was prepared following exactly the reaction condition reported by
20-22
Chakraborti and co-workers
and used without measuring the exact acid strength of the
catalyst. The reaction condition can be scaled up without loss of the yield. The analytical

samples were prepared by passing through a short pad of SiO2 and characterized by their
NMR and mass spectral analysis.
Table 1: Optimization of selective acetolysis of primary benzyl group in compound 1.
Ac2O
HClO4-SiO2
OAc
O
OBn
O
AcO
BnO
AcO
BnO
OPMP
OPMP
OBn
OBn
19
1
Sl.
Ac2O
HClO4-SiO2 Temp. Time Yield
No. Equiv.
mg/100 mg
(min) (%)
(°C)
0 °C
0 °C
0 °C
0 °C
−10 °C
RT
1
2
3
4
5
6
1.5
2.0
1.2
1.5
1.5
1.5
25
25
25
10
10
10
10
10
10
10
30
5
85
85
78
85
70
60a
a: Together with some by products.
Table 2: Selective acetolysis of primary benzyloxy groups of differentially protected
monosaccharide derivatives using acetic anhydride (1.5 equiv.) and HClO4-SiO2 (10 mg/100
mg of substrate) as solid acid catalyst.
Sl.
No.
1
Starting material
Acetolysis product
(Yield in %)
Temp. Time
(min)
10
(°C)
0 °C
OBn
AcO
OAc
AcO
O
O
BnO
OPMP
BnO
OPMP
OBn
1
OBn
19 (85%; 82%a)
OAc
OAc
2
10
BnO
AcO
0 °C
BnO
AcO
O
O
BnO
AcO
OPMP
20 (82%)
OPMP
2
OBn
OAc
3
4
5
10
10
10
0 °C
0 °C
0 °C
AcO
AllO
O
AcO
AllO
O
BnO
BnO
OMe
OMe
21 (80%)
AcO
AcO
BnO
3
BnO
AcO
BnO
OBn
O
OBn
O
OAll
OAll
22 (82%)
4
AcO
AcO OBn
O
OAc
O
AcO
AcO
OC8H17
OBn
OC8H17
OBn
23 (78%)
5

OBn
O
OAc
O
6
10
0 °C
AcO
BnO
AcO
BnO
AcO
AcO
SiMe3
O
SiMe3
O
6
24 (74%)
OBn
O
OBn
O
7
8
9
30
15
15
BnO
AcO
BnO
BnO
−15
°C
BnO
BnO
OMe
OMe
25 (80%)
7
OAc
OAc
O
BnO
AcO
AcO
RT
RT
AcO
AcO
AcO
O
OPMP
OPMP
26 (86%)
8
OBn
OAc
AcO
AcO
O
AcO
AcO
O
BzO
OMe
BzO
OMe
9
27 (90%)
OAc
O
OBn
O
10
11
RT
RT
15
15
AcO
BnO
AcO
BnO
OPMP
OPMP
OBn
OBn
28 (78%)
10
AcO OBn
AcO OAc
O
O
AllO
AllO
OPMP
OAc
OPMP
OAc
29 (80%)
OAc
11
OBn
12
13
RT
RT
20
10
BzO
BzO
O
BzO
BzO
O
BzO
BzO
OMe
30 (85%)
OMe
12
OAc
OPMB
BzO
BzO
O
BzO
BzO
O
BzO
BzO
OMe
OMe
30
(90%)
13
OBz
OBz
14
15
16
RT
RT
RT
15
15
15
AcO
BzO
BzO
BnO
BzO
BzO
O
O
OMe
31 (90%)
OMe
14
OBn
O
OAc
AcO
AcO
O
AcO
AcO
OPMP
OPMP
N3
N3
15
OBn
32 (76%)
OAc
AcO
BzO
AcO
O
O
BzO
N3
N
3 OPMP
33 (72%)
OPMP
16

OAc
O
OBn
O
17
18
RT
20
5
AcO
AcO
AcO
AcO
OAll
OAll
NPhth
34 (76%)
BnO OAc
NPhth
17
BnO OBn
0 °C
O
O
O
O
BnO
BnO
NHCbz
O
O
NHCbz
3
O
O
AcO
AcO
3
O
O
O
18
O
35 (75%)
18
a: in a scale 10 g of the substrate 1.
3.
Conclusion
In conclusion, a significantly fast, mild and convenient reaction condition has been developed
for the preparation of the selectively acetolysis products of the primary benzyloxy groups in
carbohydrate derivatives using acetic anhydride in the presence of a catalytic quantity of
HClO4-SiO2 under solvent-free conditions. This method will be considered as alternative for
the temporary protection of primary hydroxyl group with benzyl ether avoiding the
conventional bulky protecting groups such as TBDPS, TBDMS, trityl etc. A large number of
functional groups used for protecting group manipulation of carbohydrates remained
unaffected under the reaction condition. This operationally simple reaction protocol will
certainly be considered as better alternative to the reported methods and find applications in
oligosaccharide syntheses.
4.
Experimental
4.1.
General methods: All reactions were monitored by thin layer chromatography over
silica gel coated TLC plates. The spots on TLC were visualized by warming ceric sulphate
(2% Ce(SO4)2 in 2N H2SO4) sprayed plates in hot plate. Silica gel 230-400 mesh was used for
column chromatography. NMR spectra were recorded on Bruker Avance 500 MHz using
CDCl3 as solvent and TMS as internal reference unless stated otherwise. Chemical shift value
is expressed in δ ppm. The complete assignment of proton and carbon spectra was carried out
1
13
13
by using a standard set of NMR experiments, e.g. H NMR, C NMR, C DEPT 135 etc.
HRMS were recorded on a Bruker mass spectrometer. HClO4-SiO2 was prepared following
the reported method.20-22

4.2.
Preparation of HClO4-SiO2 catalyst20: HClO4 (1.8 g, 12.5 mmol, as a 70% aq.
solution) was added to a suspension of SiO2 (230-400 mesh, 23.7 g) in Et2O (70.0 mL). The
mixture was concentrated and the residue was heated at 100 °C for 72 h under vacuum to
furnish HClO4-SiO2 (0.5 mmol/g) as a free flowing powder. (50 mg = approx. 0.025 mmol of
HClO4).
4.3.
Typical reaction condition for the acetolysis of 6-benzyloxy group in
carbohydrate derivative: A mixture of compound 1 (100 mg, 0.17 mmol) in acetic
anhydride (25 µL, 1.5 mmol) was cooled to 0 °C. To the cooled reaction mixture was added
HClO4-SiO2 (10 mg) and the reaction mixture was stirred at same temperature for appropriate
time mentioned in Table 2. The reaction mixture was filtered and washed with EtOAc (15
mL) and concentrated under reduced pressure to give the product, which was passed through
a short pad of SiO2 to give analytically pure compound 19 (80 mg, 85%). Following the
similar reaction condition, a set of 6-O-acetylated products were prepared from their
corresponding 6-benzyloxy derivatives.
4.4.
Spectral data of synthesized 6-O-acetylated products:
p-Methoxyphenyl 4,6-di-O-acetyl-2,3-di-O-benzyl-β- -galactopyranoside (19): Colorless
D
1
syrup; H NMR (500 MHz, CDCl3): δ 7.27-7.24 (m, 10 H, Ar-H), 6.99 (d, J = 9.0 Hz, 2 H,
Ar-H), 6.78 (d, J = 9.0 Hz, 2 H, Ar-H), 5.49 (d, J = 3.0 Hz, 1 H, Ar-H), 4.96 (d, J = 11.5 Hz,
1 H, PhCH), 4.82 (d, J = 11.5 Hz, 1 H, PhCH), 4.80 (d, J1,2 = 9.5 Hz, 1 H, H-1), 4.74 (d, J =
11.5 Hz, 1 H, PhCH), 4.53 (d, J = 11.5 Hz, 1 H, PhCH), 4.17-4.15 (m, 2 H, H-6ab), 3.90-3.79
(m, 2 H, H-2, H-5), 3.77 (s, 3 H, OCH3), 3.59 (dd, J2,3;3,4 = 9.5, 3.5 Hz, 1 H, H-3), 2.17 (s, 3
13
H, COCH3), 2.07 (s, 3 H, COCH3); C NMR (125 MHz, CDCl3): δ 170.1 (COCH3), 170.0
(COCH3), 155.5-114.5 (Ar-C), 103.1 (C-1), 79.0 (C-3), 78.5 (C-4), 75.5 (PhCH2), 72.2
(PhCH2), 70.9 (C-5), 66.2 (C-2), 61.9 (C-6), 55.5 (OCH3), 20.8 (COCH3), 20.7 (COCH3);
HRMS [M+Na]+: 573.2101 (calcd.); found: 573.2092 (found).
p-Methoxyphenyl 2,3,6-tri-O-acetyl-4-O-benzyl-α- -mannopyranoside (20): Colorless
D
syrup; 1H NMR (500 MHz, CDCl3): δ 7.40-7.20 (m, 5 H, Ar-H), 6.98 (d, J = 9.0 Hz, 2 H, Ar-
H), 6.78 (d, J = 9.0 Hz, 2 H, Ar-H), 5.53 (dd, J2,3;3,4 = 3.0, 9.5 Hz, 1 H, H-3), 5.34-5.32 (m, 1
H, H-2), 5.28 (br s, 1 H, H-1), 4.70 (d, J = 11.5 Hz, 1 H, PhCH), 4.60 (d, J = 11.5 Hz, 1 H,
PhCH), 4.30-4.28 (m, 2 H, H-6ab), 4.07-4.04 (m, 1 H, H-5), 3.83 (t, J3,4;4,5 = 9.5 Hz each, 1 H,
H-4), 3.75 (s, 3 H, OCH3), 2.16 (s, 3 H, COCH3), 2.03 (s, 3 H, COCH3), 1.99 (s, 3 H,
COCH3); 13C NMR (125 MHz, CDCl3): δ 170.1 (COCH3), 169.5 (COCH3), 169.3 (COCH3),

155.3-114.5 (Ar-C), 96.6 (C-1), 74.8 (PhCH2), 73.0 (C-5), 71.6 (C-3), 70.1 (C-2), 69.9 (C-4),
62.8 (C-6), 55.4 (OCH3), 20.9 (OCH3), 20.8 (COCH3), 20.7 (COCH3); HRMS [M+Na]+:
525.1737 (calcd.); 525.1747 (found).
Methyl 4,6-di-O-acetyl-3-O-allyl-2-O-benzyl-α- -glucopyranoside (21): Colorless syrup;
D
1H NMR (500 MHz, CDCl3): δ 7.34-7.26 (m, 5 H, Ar-H), 5.90-5.81 (m, 1 H, CH=CH2), 5.25-
5.11 (m, 2 H, CH=CH2), 4.91 (t, J3,4;4,5 = 10.0 Hz each, 1 H, H-4), 4.79 (d, J = 11.5 Hz, 1 H,
PhCH), 4.62 (d, J = 11.5 Hz, 1 H, PhCH), 4.54 (d, J1,2 = 3.5 Hz, 1 H, H-1), 4.34-4.30 (m, 1 H,
OCH), 4.19 (dd, J6a,6b;6a,5 = 12.0, 5.0 Hz, 1 H, H-6a), 4.13-4.08 (m, 1 H, OCH), 3.99 (dd,
J6a,6b;6b,5 = 12.0, 2.0 Hz, 1 H, H-6b), 3.81-3.78 (m, 1 H, H-5), 3.75 (t, J2,3;3,4 = 9.5 Hz each, 1
H, H-3), 3.49 (dd, J1,2;2,3 = 3.0, 9.5 Hz, 1 H, H-2), 3.36 (s, 3 H, OCH3), 2.06 (s, 3 H, COCH3);
13C NMR (125 MHz, CDCl3): δ 170.3 (COCH3), 169.2 (COCH3), 137.9-116.6 (Ar-C), 98.3
(C-1), 79.3 (C-3), 78.7 (C-4), 74.1 (PhCH2), 73.5 (OCH2), 69.8 (C-5), 67.6 (C-2), 62. 2 (C-6),
55.3 (OCH3), 20.9 (COCH3), 20.8 (COCH3); HRMS [M+Na]+: 431.1682 (calcd.); 431.1673
(found).
Allyl 4,6-di-O-acetyl-2,3-di-O-benzyl-α-
-glucopyranoside (22): Colorless syrup; 1H NMR
D
(500 MHz, CDCl3): δ 7.35-7.20 (m, 10 H, Ar-H), 5.86-5.80 (m, 1 H, CH=CH2), 5.39 (t, J3,4;4,5
= 10.0 Hz each, H-4), 5.23-5.16 (m, 2 H, CH=CH2), 4.85 (d, J1,2 = 10.0 Hz, 1 H, H-1), 4.74
(d, J = 12.0 Hz, 1 H, PhCH), 4.67 (d, J = 12.0 Hz, 1 H, PhCH), 4.56 (d, J = 12.0 Hz, 1 H,
PhCH), 4.47 (d, J = 12.0 Hz, 1 H, PhCH), 4.19 (dd, J6a,6b;6a,5 = 12.0, 5.0 Hz, 1 H, H-6a), 4.14-
4.08 (m, 2 H, OCH2), 3.95 (dd, J6a,6b;6b,5 = 12.0, 2.5 Hz, 1 H, H-6b), 3.82-3.80 (m, 2 H, H-3,
13
H-5), 3.78 (br s, 1 H, H-2), 2.07 (s, 3 H, COCH3), 1.99 (s, 3 H, COCH3); C NMR (125
MHz, CDCl3): δ 170.4 (COCH3), 169.3 (COCH3), 138.1-127.3 (Ar-C), 117.6 (CH=CH2),
97.5 (C-1), 77.2 (C-5), 74.1 (C-3), 72.8 (PhCH2), 71.9 (PhCH2), 69.3 (C-4), 68.1 (OCH2),
68.0 (C-2), 62.9 (C-6), 20.8 (COCH3), 20.7 (COCH3); HRMS [M+Na]+: 507.1995 (calcd.);
507.2004 (found).
Octyl 3,4,6-tri-O-acetyl-2-O-benzyl-β-
-galactopyranoside (23): Colorless syrup; 1H NMR
D
(500 MHz, CDCl3): δ 7.31-7.23 (m, 5 H, Ar-h), 5.30 (d, J3,4;4,5 = 3.0 Hz each, 1 H, H-4), 4.93
(dd, J2,3;3,4 = 9.5, 3.0 Hz, 1 H, H-3), 4.87 (d, J = 11.5 Hz, 1 H, PhCH), 4.60 (d, J = 11.5 Hz, 1
H, PhCH), 4.43 (d, J1,2 = 8.0 Hz, 1 H, H-1), 4.13-4.07 (m, 2 H, H-6ab), 3.96-3.90 (m, 1 H,
OCH), 3.84-3.80 (m, 1 H, H-5), 3.59-3.50 (m, 2 H, H-2, OCH), 2.09 (s, 3 H, COCH3), 2.03
(COCH3), 1.93 (s, 3 H, COCH3), 1.68-1.60 (m, 2 H, CH2), 1.40-1.20 (m, 10 H, CH2), 0.87 (t,
13
J = 7.0 Hz, 3 H, CH3); C NMR (125 MHz, CDCl3): δ 169.9 (COCH3), 169.8 (COCH3),

169.6 (COCH3), 138.3-127.5 (Ar-C), 103.8 (C-1), 76.3 (C-3), 74.6 (PhCH2), 72.1 (C-4), 70.4
(OCH2), 70.3 (C-5), 67.3 (C-2), 61.2 (C-6), 31.8 (CH2), 29.7 (CH2), 29.4 (CH2), 29.1 (CH2),
25.8 (CH2), 22.6 (CH2), 20.7 (COCH3), 20.6 (2 C, 2 COCH3), 14.4 (CH3); HRMS [M+Na]+:
531.2570 (calcd.); 531.2561 (found).
2-Trimethylsilylethyl 2,4,6-tri-O-acetyl-3-O-benzyl-α- -glucopyranoside (24): Colorless
D
1
syrup; H NMR (500 MHz, CDCl3): δ 7.28-7.15 (m, 5 H, Ar-H), 5.00 (d, J1,2 = 3.5 Hz, 1 H,
H-1), 4.98 (t, J3,4;4,5 = 9.5 Hz each, 1 H, H-4), 4.76 (dd, J1,2;2,3 = 3.0, 9.5 Hz, 1 H, H-2), 4.63
(d, J = 11.5 Hz, 1 H, PhCH), 4.52 (d, J = 11.5 Hz, 1 H, PhCH), 4.09 (dd, J6a,6b;6a,5 = 12.5, 5.0
Hz, 1 H, H-6a), 3.97 (dd, J6a,6b;6b,5 = 12.5, 2.5 Hz, 1 H, H-6b), 3.88 (t, J2,3;3,4 = 9.5 Hz each, 1
H, H-3), 3.83-3.79 (m, 1 H, H-5), 3.76-3.71 (m, 1 H, OCH), 3.48-3.40 (m, 1 H, OCH), 2.02
(s, 3 H, COCH3), 1.98 (s, 3 H, COCH3), 1.88 (s, 3 H, COCH3), 0.87-0.77 (m, 2 H, CH2), 0.00
13
(s, 9 H, Si(CH3)3); C NMR (125 MHz, CDCl3): δ 170.3 (COCH3), 170.1 (COCH3), 169.8
(COCH3), 137.1-126.0 (Ar-C), 96.0 (C-1), 75.0 (C-5), 73.6 (PhCH2), 68.4 (C-3), 67.5 (C-4),
64.0 (2 C, C-2, OCH2), 61.9 (C-6), 25.6 (CH2), 20.9 (2 C, 2 COCH3), 20.8 (COCH3); HRMS
[M+Na]+: 519.2027 (calcd.); 519.2016 (found).
1
Methyl 6-O-acetyl-2,3,4-tri-O-benzyl-α-
D
-mannopyranoside (25): Colorless syrup; H
NMR (500 MHz, CDCl3): δ 7.33-7.16 (m, 15 H, Ar-H), 4.91 (d, J = 11.0 Hz, 1 H, PhCH),
4.71-4.68 (m, 2 H, 2 PhCH), 4.59-4.55 (m, 3 H, H-1, 2 PhCH), 4.32-4.22 (m, 2 H, H-4,
PhCH), 3.89-3.88 (m, 1 H, H-5), 3.87-3.81 (m, 2 H, H-6ab), 3.74-3.72 (m, 2 H, H-2, H-3),
3.30 (s, 3 H, OCH3), 2.04 (s, 3 H, COCH3); 13C NMR (125 MHz, CDCl3): δ 170.5 (COCH3),
138.3-127.6 (Ar-C), 98.9 (C-1), 80.2 (C-5), 75.3 (PhCH2), 74.5 (2 C, C-3, C-4), 72.6
(PhCH2), 72.1 (PhCH2), 70.0 (C-2), 63.1 (C-6), 54.7 (OCH3), 20.8 (COCH3); HRMS
[M+Na]+: 529.2203 (calcd.); 529.2212 (found).
1
p-Methoxyphenyl 2,3,4,6-tetra-O-acetyl-α-
D
-mannopyranoside (26): Colorless syrup; H
NMR (500 MHz, CDCl3): δ 7.18 (d, J = 9.0 Hz, 2 H, Ar-H), 6.80 (d, J = 9.0 hz, 2 H, Ar-H),
5.51 (dd, J2,3;3,4 = 3.0, 9.5 Hz, 1 H, H-3), 5.39 (br s, 1 H, H-2), 5.37 (br s, 1 H, H-1), 5.29 (t,
J3,4;4,5 = 9.5 Hz each, 1 H, H-4), 4.26 (dd, J6a,6b;6a,5 = 12.0, 4.0 Hz, 1 H, H-6a), 4.12-4.09 (m, 1
H, H-5), 4.05 (dd, J6a,6b;6b,5 = 12.0, 2.0 Hz, 1 H, H-6b), 3.76 (s, 3 H, OCH3), 2.19 (s, 3 H,
COCH3), 2.05 (s, 3 H, COCH3), 2.04 (s, 3 H, COCH3), 2.02 (s, 3 H, COCH3); 13C NMR (125
MHz, CDCl3): δ 170.1 (COCH3), 169.6 (COCH3), 169.5 (COCH3), 169.4 (COCH3), 155.4-
114.6 (Ar-C), 96.6 (C-1), 69.5 (C-5), 69.0 (C-3), 68.9 (C-4), 66.0 (C-2), 62.1 (C-6), 55.4

(OCH3), 20.8 (COCH3), 20.7 (2 C, 2 COCH3), 20.6 (COCH3); HRMS [M+Na]+: 477.1373
(calcd.); 477.1380 (found).
1
Methyl 3,4,6-tri-O-acetyl-2-O-benzoyl-α-
D
-glucopyranoside (27): Colorless syrup; H
NMR (500 MHz, CDCl3): δ 7.60-7.27 (m, 5 H, Ar-H), 5.69 (t, J2,3;3,4 = 10.0 Hz each, 1 H, H-
3), 5.15 (t, J3,4;4,5 = 9.5 Hz each, 1 H, H-4), 5.13 (d, J1,2 = 3.5 Hz, 1 H, H-1), 5.07 (dd, J1,2;2,3
3.5, 9.5 Hz, 1 H, H-2), 4.31 (dd, J6a,6b;6a,5 = 12.0, 5.0 Hz, 1 H, H-6a), 4.13 (dd, J6a,6b;6b,5
=
=
12.0, 2.5 Hz, 1 H, H-6b), 4.08-4.03 (m, 1 H, H-5), 3.40 (s, 3 H, OCH3), 2.12 (s, 3 H, COCH3),
2.06 (s, 3 H, COCH3), 1.95 (s, 3 H, COCH3); 13C NMR (125 MHz, CDCl3): δ 170.7
(COCH3), 170.2 (COCH3), 169.6 (COCH3), 165.7 (COPh), 133.5-128.6 (Ar-C), 96.9 (C-1),
71.6 (C-5), 70.0 (C-4), 68.4 (C-3), 67.2 (C-2), 61.9 (C-6), 55.5 (OCH3), 20.7 (COCH3), 20.6
(COCH3), 20.5 (COCH3); HRMS [M+Na]+: 447.1267 (calcd.); 447.1276 (found).
p-Methoxyphenyl 4,6-di-O-acetyl-2,3-di-O-benzyl-β- -glucopyranoside (28): Colorless
D
1
syrup; H NMR (500 MHz, CDCl3): δ 7.33-7.17 (m, 10 H, Ar-H), 7.17 (d, J = 9.0 Hz, 2 H,
Ar-H), 6.80 (d, J = 9.0 Hz, 2 H, Ar-H), 5.07-5.00 (m, 2 H, H-4, PhCH), 4.85-4.78 (m, 2 H, H-
1, PhCH), 4.62-4.60 (m, 2 H, 2 PhCH), 4.25-4.18 (m, 1 H, H-6a), 4.10-4.07 (m, 1 H, H-6b),
3.77 (s, 3 H, OCH3), 3.71 (t, J2,3;3,4 = 9.5 Hz each, 1 H, H-3), 3.65-3.58 (m, 2 H, H-2, H-5),
2.11 (s, 3 H, COCH3), 1.91 (s, 3 H, COCH3); 13C NMR (125 MHz, CDCl3): δ 169.3
(COCH3), 168.1 (COCH3), 154.5-113.4 (Ar-C), 101.8 (C-1), 80.6 (C-5), 80.4 (C-4), 74.1 (2
C, 2 PhCH2), 70.9 (C-3), 67.9 (C-2), 61.2 (C-6), 54.5 (OCH3), 20.0 (COCH3), 19.9 (COCH3);
HRMS [M+Na]+: 573.2101 (calcd.); 573.2092 (found).
p-Methoxyphenyl 2,4,6-tri-O-acetyl-3-O-allyl-β-D-galactopyranoside
(29): Colorless
syrup; 1H NMR (500 MHz, CDCl3): δ 6.96 (d, J = 9.0 hz, 2 H, Ar-H), 6.80 (d, J = 9.0 Hz, 2
H, Ar-H), 5.82-5.74 (m, 1 H, CH=CH2), 5.43 (dd, J3,4;4,5 = 2.5 Hz each, 1 H, H-4), 5.27 (t,
J1,2;2,3 = 9.5 Hz each, 1 H, H-2), 5.23-5.16 (m, 2 H, CH=CH2), 4.82 (d, J1,2 = 9.5 Hz, 1 H, H-
1), 4.18-4.12 (m, 3 H, H-6a, OCH2), 3.93-3.87 (m, 2 H, H-5, H-6b), 3.76 (s, 3 H, OCH3), 3.55
(dd, J2,3;3,4 = 9.5, 3.0 Hz, 1 H, H-3), 2.17 (s, 3 H, COCH3), 2.09 (s, 3 H, COCH3), 2.06 (s, 3 H,
COCH3); 13C NMR (125 MHz, CDCl3): δ 170.1 (COCH3), 170.0 (COCH3), 168.9 (COCH3),
155.6-114.4(Ar-C), 100.8 (C-1), 76.3 (C-3), 71.1 (C-4), 70.5 (OCH2 ), 70.3 (C-5), 65.7 (C-2),
61.8 (C-6), 55.5 (OCH3), 20.8 (COCH3), 20.7 (COCH3), 20.6 (COCH3); HRMS [M+Na]+:
475.1580 (calcd.); 475.1590 (found).
1
Methyl 6-O-acetyl-2,3,4-tri-O-benzoyl-α-
D
-glucopyranoside (30): Colorless syrup; H
NMR (500 MHz, CDCl3): δ 7.90-7.27 (m, 15 H, Ar-H), 6.10 (t, J2,3;3,4 = 9.5 Hz, 1 H, H-3),

5.57 (t, J3,4;4,5 = 9.5 Hz each, 1 H, H-4), 5.25 (dd, J1,2;2,3 = 3.5, 9.5 Hz, 1 H, H-2), 5.22 (d, J1,2
= 3.5 Hz, 1 H, H-1), 4.31-4.20 (m, 3 H, H-5, H-6ab), 3.48 (s, 3 H, OCH3), 2.07 (s, 3 H,
COCH3); 13C NMR (125 MHz, CDCl3): δ 170.2 (COCH3), 165.6 (2 C, 2 COPh), 165.1
(COPh), 133.3-128.2 (Ar-C), 97.1 (C-1), 71.9 (C-5), 70.3 (C-3), 69.2 (C-4), 67.5 (C-2), 62.4
(C-6), 55.6 (OCH3), 20.7 (COCH3); HRMS [M+Na]+: 571.1580 (calcd.); 571.1589 (found).
1
Methyl 6-O-acetyl-2,3,4-tri-O-benzoyl-α-
D
-mannopyranoside (31): Colorless syrup; H
NMR (500 MHz, CDCl3): δ 8.15-7.23 (m, 15 H, Ar-H), 5.88 (t, J3,4;4,5 = 9.5 Hz each, 1 H, H-
4), 5.84 (dd, J2,3;3,4 = 3.0, 9.5 Hz, 1 H, H-3), 5.63-5.62 (m, 1 H, H-2), 4.96 (br s, 1 H, H-1),
13
4.34-4.24 (m, 3 H, H-5, H-6ab), 3.54 (s, 3 H, OCH3), 2.01 (s, 3 H, COCH3); C NMR (125
MHz, CDCl3): δ 170.2 (COCH3), 165.3 (COPh), 165.2 (COPh), 165.1 (COPh), 133.4-128.2
(Ar-C), 98.6 (C-1), 70.3 (C-5), 69.8 (C-3), 68.5 (C-2), 67.0 (C-4), 62.8 (C-6), 55.5 (OCH3),
20.6 (COCH3); HRMS [M+Na]+: 571.1580 (calcd.); 571.1589 (found).
p-Methoxyphenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-galactopyranoside
(32):
Colorless syrup; 1H NMR (500 MHz, CDCl3): δ 6.84 (d, J = 9.0 Hz, 2 H, Ar-H), 6.72 (d, J =
9.0 Hz, Ar-H), 5.83 (dd, J2,3;3,4 = 9.5, 3.0 Hz, 1 H, H-3), 5.78 (d, J1,2 = 10.0 Hz, 1 H, H-1),
5.49 (dd, J3,4;4,5 = 2.5 Hz each, 1 H, H-4), 4.74 (dd, J1,2;2,3 = 9.5 Hz each, 1 H, H-2), 4.25-4.09
(m, 3 H, H-5, H-6ab), 3.72 (s, 3 H, OCH3), 2.24 (s, 3 H, COCH3), 2.06 (s, 3 H, COCH3), 1.88
13
(s, 3 H, COCH3); C NMR (125 MHz, CDCl3): δ 170.0 (COCH3), 169.9 (2 C, 2 COCH3),
155.3-114.4 (Ar-C), 97.9 (C-1), 71.0 (C-3), 68.0 (C-4), 66.5 (C-5), 61.2 (C-6), 55.4 (OCH3),
51.3 (C-2), 20.7 (COCH3), 20.6 (COCH3), 20.5 (COCH3); HRMS [M+Na]+: 460.1332
(calcd.); 460.1343 (found).
p-Methoxyphenyl 4,6-di-O-acetyl-2-azido-3-O-benzoyl-2-deoxy-α- -galactopyranoside
D
1
(33): Colorless syrup; H NMR (500 MHz, CDCl3): δ 8.0-6.82 (m, 9 H, Ar-H), 5.79 (dd,
J2,3;3,4 = 9.5, 3.0 Hz, 1 H, H-3), 5.69 (dd, J3,4;4,5 = 2.5 Hz each, 1 H, H-4), 5.55 (d, J1,2 = 3.5
Hz, 1 H, H-1), 4.50-4.47 (m, 1 H, H-5), 4.18-4.07 (m, 2 H, H-6ab), 3.90 (dd, J1,2;2,3 = 9.5, 3.5
Hz, 1 H, H-2), 3.78 (s, 3 H, OCH3), 2.12 (s, 3 H, COCH3), 1.99 (s, 3 H, COCH3); 13C NMR
(125 MHz, CDCl3): δ 169.9 (COCH3), 169.4 (COCH3), 165.1 (COPh), 155.7-114.6 (Ar-C),
98.2 (C-1), 68.7 (C-3), 67.6 (C-4), 67.5 (C-2), 61.4 (C-6), 57.8 (C-5), 55.5 (OCH3), 20.6
(COCH3), 20.5 (COCH3); HRMS [M+Na]+: 522.1489 (calcd.); 522.1480 (found).
Allyl 3,4,6-tri-O-acetyl-2-deoxy-2-N-phthalimido-β- -glucopyranoside (34): Colorless
D
syrup; 1H NMR (500 MHz, CDCl3): δ 7.73-7.70 (m, 4 H, Ar-H), 5.75 (t, J = 9.5 Hz, 1 H, H-
3), 5.73-5.68 (m, 1 H, CH=CH2), 5.39 (d, J = 8.5 Hz, 1 H, H-1), 5.15 (t, J = 9.0 Hz, 1 H, H-

2), 5.14-5.06 (m, 2 H, CH=CH2), 4.33-4.25 (m, 3 H, H-4, H-6a, OCH), 4.16-4.13 (m, 1 H,
OCH), 4.05 (dd, J = 12.0, 2.5 Hz, 1 H, H-6b), 3.85-3.82 (m, 1 H, H-5), 2.11 (s, 3 H, COCH3),
2.02 (s, 3 H, COCH3), 1.86 (s, 3 H, COCH3); 13C NMR (125 MHz, CDCl3): δ 170.3
(COCH3), 169.9 (COCH3), 169.1 (COCH3), 134.1-117.9 (Ar-C), 97.1 (C-1), 71.9 (C-5), 70.8
(C-3), 70.0 (C-4), 68.9 (OCH2), 61.9 (C-6), 54.5 (C-2), 20.7 (COCH3), 20.6 (COCH3), 20.4
(COCH3); HRMS [M+Na]+: 498.1376 (calcd.); 498.1385 (found).
3-(N-Benzyloxycarbonyl)aminopropyl
(4-O-acetyl-2,3-O-isopropylidene-α- -rhamno-
L
1
pyranosyl)-(1→3)-6-O-acetyl-2,4-di-O-benzyl-α-
D
-galactopyranoside (35): H NMR (500
MHz, CDCl3): δ 7.34-7.28 (m, 15 H, Ar-H), 5.38 (br s, 1 H, H-1B), 5.25-5.14 (m, 2 H,
PhCH2Cbz), 4.84-4.76 (m, 3 H, H-1A, H-4B, NH), 4.64-4.58 (m, 3 H, 3 PhCH), 4.16-4.09 (m,
4 H, H-3A, H-3B, H-6aA, PhCH), 4.07-4.01 (m, 2 H, H-6bA, OCH), 3.97 (dd, J = 9.5 Hz, 3.5
Hz, 1 H, H-2A), 3.92 (m, 1 H, H-5A), 3.83-3.79 (m, 2 H, H-2B, H-5B), 3.78-3.73 (m, 1 H,
OCH), 3.71 (br s, 1 H, H-4A), 3.64-3.58 (m, 1 H, NCH), 3.42-3.35 (m, 1 H, NCH), 2.09 (s, 3
H, COCH3), 1.98 (s, 3 H, COCH3), 1.88-1.76 (m, 2 H, CH2), 1.53 (s, 3 H, CCH3), 1.34 (s, 3
13
H, CCH3), 1.15 (d, J = 6.0 Hz, 3 H, CCH3); C NMR (125 MHz, CDCl3): δ 172.4 (COO-),
170.0 (COCH3), 169.5 (COCH3), 138.2-127.8 (Ar-C), 109.6 (C(CH3)2), 98.8 (C-1A), 97.0 (C-
1B), 77.3, 76.8, 76.0, 75.8, 75.6 (PhCH2), 74.8, 74.4, 72.5 (PhCH2), 68.7, 68.4 (PhCH2), 66.1
(C-6A), 64.8, 63.4 (OCH2), 41.6 (NCH2), 28.8 (CH2), 27.7 (CCH3), 26.7 (CCH3), 20.9
(COCH3), 20.6 (COCH3), 16.7 (CCH3); HRMS [M+Na]+: 844.3521 (calcd.); 844.3530
(found).
5.
Acknowledgement
M.K. thanks CSIR, New Delhi for providing senior research fellowship. This work was
supported by SERB, New Delhi (Project No. EMR/2015/000282) (AKM).
6.
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Research Highlights
•
•
•
•
•
A convenient methodology for the selective acetolysis of primary benzyloxy groups.
The reaction condition is significantly fast, mild and highly selective.
A catalytic quantity of HClO4-SiO2 is required avoiding organic solvents.
HClO4-SiO2 has been used as a solid acid catalyst.
Most of the functional groups used in carbohydrates remained unaffected.

Conflicts of Interest
There are no conflicts to declare.