Supramolecular stacking motifs in the solid state of amide and triazole derivatives of cellobiose

Article abstract of DOI:10.1016/j.carres.2014.02.011

1-Acetamido-1-deoxy-(4-O-β-d-glucopyranosyl-β-d-glucopyranose) (5) and 1-deoxy-1-(4-phenyl-1,2,3-triazolyl)-(4-O-β-d-glucopyranosyl- β-d-glucopyranose) (7) were synthesised from 1-azido-1-deoxy-(4-O-β-d- glucopyranosyl-β-d-glucopyranose) (2) and crystalli

Full text of DOI:10.1016/j.carres.2014.02.011

Carbohydrate Research 388 (2014) 67–72
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Supramolecular stacking motifs in the solid state of amide
and triazole derivatives of cellobiose
John A. Hayes a, Kevin S. Eccles a, Simon J. Coles b, Simon E. Lawrence a, Humphrey A. Moynihan a,
⇑
a Department of Chemistry/Analytical and Biological Chemistry Research Facility/Synthesis and Solid State Pharmaceutical Centre, University College Cork, College Road, Cork, Ireland
b UK National Crystallographic Service, Chemistry, Faculty of Natural and Environmental Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
1-Acetamido-1-deoxy-(4-O-b-
D
-glucopyranosyl-b-
-glucopyranose) (7) were synthesised from 1-azido-1-deoxy-
-glucopyranose) (2) and crystallised as dihydrates. Crystal structural
analysis of 5ꢀ2H2O displayed an acetamide C(4) chain and stacked cellobiose residues. The structure of
7ꢀ2H2O featured stacking and stacking of the cellobiose residues.
Ó 2014 Elsevier Ltd. All rights reserved.
D-glucopyranose) (5) and 1-deoxy-1-(4-phenyl-1,2,
Received 12 December 2013
Received in revised form 29 January 2014
Accepted 7 February 2014
3-triazolyl)-(4-O-b-
D-glucopyranosyl-b-D
(4-O-b- -glucopyranosyl-b-
D
D
Available online 18 February 2014
p–p
Keywords:
Cellobiose
Crystal structure
Sugar amide
Sugar triazole
Cellobiose derivatives have been extensively studied as small-
molecule models for cellulose because the crystal chemistry of
these compounds can be more readily investigated then that of cel-
lulose itself.1 Key features that are examined include the pyranose
ring puckering, torsional angles for the primary hydroxyl groups
and acetal linkages,2 and supramolecular features such as
hydrogen bonding motifs.3 Examples of cellobiose derivatives
designed to act as cellulose fragments include methyl 4-O-
Another group, 1,2,3-triazoles, have been exploited in the crystal
engineering of metal-organic frameworks (MOFs),12 in particular,
and as supramolecular hydrogen bonding acceptors.13 Both groups
can be obtained readily from azides.
In addition to providing small-molecule cellulose analogues,
cellobioses functionalised with groups with strong propensities
for forming supramolecular motifs will also further investigation
of the crystal engineering of sugars. For sugars, crystal state prop-
erties affect issues such as hygroscopicity, flow, blending, and com-
pression into tablets.14 An ability to control the molecular
assembly of sugar molecules in crystalline solids in a rational
manner would have applications in areas such as pharmaceutical
formulation. In the work described here, acetamido and
4-phenyl-1,2,3-triazolyl derivatives of cellobiose have been
synthesised and the crystal chemistry of these compounds exam-
ined. Both groups give rise to supramolecular stacking motifs with
potential for exploitation in crystal engineering.
methyl-b-
D
-glucopyranosyl-(1-4)-b-
D
-glucopyranoside4 and cyclo-
hexyl 40-O-cyclohexyl b-
D
-cellobioside.5
One approach to designing such compounds would be to couple
cellobiose to groups which provide well established supramolecu-
lar motifs for crystal engineering. Crystal engineering exploits
structural units known as supramolecular synthons which assem-
ble by known intermolecular interactions or motifs.6 Amides,
which form well known hydrogen bonded networks in the solid
state, are good examples of such synthons.7 For example, second-
ary amides often form hydrogen bonded chains in crystal struc-
tures between the amide NAH and carbonyl groups.8 As these
chains consist of a repeating unit containing four atoms linked
by NAHꢀ ꢀ ꢀO@C hydrogen bonds, they can be labelled as C(4) chains
using Etter’s notation for describing hydrogen bonding motifs.9
Such hydrogen bonding motifs occur in many amido-sugars
including acetamido-lactoses,10 and N-glycoprotein models.11
1-Acetamido-1-deoxy-(4-O-b-
nose) (5) and 1-deoxy-1-(4-phenyl-1,2,3-triazolyl)-(4-O-b-
copyranosyl-b- -glucopyranose) (7) were prepared from the
D
-glucopyranosyl-b-
D-glucopyra-
D-glu-
D
corresponding azide (2)15 which was in turn obtained from the
bromide (1) as outlined in Scheme 1. Hydrogenation of azide (2)
over Pd/C at 200 psi gave the amine (3) as a single epimer.
N-Acetylation followed by O-deacetylation gave the target acetam-
ido-cellobiose (5). Triazole (6) was obtained by Cu(I) catalysed
azide 1,3-dipolar cycloaddition to phenylacetylene with micro-
wave assistance.16 Deacetylation of (6) gave the second target
compound, triazolyl-cellobiose (7).
⇑
Corresponding author. Tel.: +353 21 4902488; fax: +353 21 4274097.
E-mail address: h.moynihan@ucc.ie (H.A. Moynihan).
http://dx.doi.org/10.1016/j.carres.2014.02.011
0008-6215/Ó 2014 Elsevier Ltd. All rights reserved.

68
J. A. Hayes et al. / Carbohydrate Research 388 (2014) 67–72
Crystals of compounds (5) and (7) suitable for single-crystal
X-ray diffraction were grown by slow evaporation from aqueous
methanol. Both compounds were found to be dihydrates and their
crystallographic data are given in Table 1. Endotherms correspond-
ing to the loss of water molecules were observed in the DSC of both
materials with corresponding mass loss in TGA (Supplementary
Material). Features common to both structures include donation
by the 3-OH of the reducing glucopyranose to the oxygen of the
non-reducing glucopyranose, forming a 7 atom hydrogen bonded
ring [an S(7) motif in Etter’s notation9] (Figs. 1 and 2), a common
feature reported in a number of cellulose polymorphs17 and
OAc
OAc
AcO
AcO
O
O
AcO
O
AcO
Br
OAc
1
a
OAc
OAc
O
AcO
AcO
O
O
Figure 1. View of the crystal structure of compound (5) dihydrate showing S(7)
intramolecular hydrogen bonding [O12H12ꢀ ꢀ ꢀO22], and C(7) and C(8) intermolec-
ular hydrogen bonding motifs [O24H24ꢀ ꢀ ꢀO27 and O15H15ꢀ ꢀ ꢀO11 respectively].
N3
AcO
AcO
OAc
2
b
e
models.18,19 The conformation of the both rings in both structures
is the 4C1 chair conformation typical of glucopyranoses.19,20 The
angle and surrounding torsional angles at the acetal oxygens link-
ing the two glucopyranose rings in both structures are typical for
small molecule cellulose analogues.19,20 There are close packing
contacts of 2.1 Å between H-10 and H-4 in both structures with
both CAH bonds axial and approximately parallel, consistent with
the geometry of the acetal linkage. These bonds would correspond
to a twofold screw axis if present in an extended cellulose-like
polymer, that is glucopyranose residues in alternating orienta-
tions.19 In both structures, the conformation of the primary hydro-
xyl in the non-reducing glucopyranose is gauche-trans and that in
the reducing glucopyranose is gauche-gauche, these being typical
conformations for small molecule cellulose analogues.19,20
OAc
OAc
O
AcO
AcO
O
OAc
O
NH2
AcO
Ph
N
OR
OR
O
OAc
RO
RO
O
3
c
O
N
RO
N
OR
OR
6, R=Ac
7, R=H
d
OR
OR
RO
RO
O
O
NHAc
RO
O
OR
OR
4, R=Ac
5, R=H
d
Scheme 1. (a) NaN3, DMSO, 1 h; (b) H2, 10% Pd/C, 9:1 MeOH/THF, 200 psi, 16 h; (c)
Ac2O, pyridine, THF, reflux, 24 h; (d) KOMe, MeOH, 4 h; (e) phenylacetylene,
CuSO4ꢀ5H2O (10 mol %), sodium ascorbate (15 mol %), DMF, MW (300 W), 80 °C,
30 min.
Compound (5) crystallised with one acetamidocellobiose mole-
cule and two unique water molecules per unit cell. The acetamido-
cellobiose molecules are stacked upon each other with an amide
C(4) hydrogen bonding motif (Fig. 3). Hence, the amide C(4) pro-
vides a supramolecular stacking motif which guides the packing
of the modified cellobiose molecules. The amide bond torsional
angles /N and WN (defined by Loganathan and co-workers11) are
ꢁ101.63° and 174.73° respectively. The WN value is in the range
observed for amidodeoxyglucose models of glycoamide linkages,
while the /N value is marginally higher than those reported.11
The 6-OH of the reducing glucopyranose donates a hydrogen
bond to the 2-OH of the reducing glucopyranose of an adjacent
molecule, forming a C(8) hydrogen bonded chain motif (Fig. 1).
Similarly, the 3-OH of the non-reducing end donates a hydrogen
bond to the 6-OH of the non-reducing glucopyranose of the same
adjacent molecules, forming a C(7) chain (Fig. 1). Hence, each ace-
tamidocellobiose has one intramolecular hydrogen bond, intermo-
lecular amide hydrogen bonds to the molecules ‘above and below’
(the supramolecular stacking motif), and intermolecular hydrogen
bonds to the molecules on either side. The intermolecular hydro-
gen bond from 3-OH to 6-OH is typical of cellulose forms,18 while
the 6-OH to 2-OH bonding is observed in some model com-
Table 1
Crystallographic data for compounds 5 and 7
Compound reference
Chemical formula
Formula Mass
Crystal system
a/Å
5ꢀ2H2O
7ꢀ2H2O
C
14H25NO11ꢀ2H2O C20H27N3O10ꢀ2H2O
419.38
Triclinic
5.0161(8)
7.6405(11)
12.965(2)
89.437(5)
86.681(5)
74.033(5)
476.91(13)
300(2)
505.48
Monoclinic
10.813(2)
4.9094(9)
21.507(4)
90
97.769(8)
90
1131.2(4)
100(2)
P21
b/Å
c/Å
a
/°
b/°
/°
c
Unit cell volume/Å3
Temperature/K
Space group
P1
1
No. of formula units per unit cell, Z
Radiation type
2
Mo K
a
Mo Ka
0.123
11924
2884
0.0640
0.0489
0.0897
0.0567
0.0925
1.139
Absorption coefficient,
l
/mmꢁ1
0.130
4647
1661
0.0224
0.0273
0.0769
0.0313
0.0928
1.176
No. of reflections measured
No. of independent reflections
Rint
pounds.19 The amidocellobiose molecules pack in
arrangement which is slightly tilted, consistent with the 6-OH to
2-OH bonding. The two water molecules are involved in
a parallel
Final R1 values (I > 2r(I))
Final wR(F2) values (I > 2
Final R1 values (all data)
r(I))
a
Final wR(F2) values (all data)
Goodness of fit on F2
one-dimensional chain of hydrogen bonding running through the
structure.

J. A. Hayes et al. / Carbohydrate Research 388 (2014) 67–72
69
Figure 2. Intramolecular S(7) and intermolecular hydrogen bonds between 6-OH groups in the structure of compound (7).
Figure 3. Hydogen bonded amide C(4) chain motif [N7H7ꢀ ꢀ ꢀO9] in the crystal structure of compound (5) dihydrate.
Compound (7) crystallised with two triazole and four water
molecules per unit cell and the two triazole molecules are related
the phenyl rings being 4.9 Å. This gives rise to anti-parallel
p-stacked columns related by the 21 axis (Fig. 4), constituting a
by a 21 screw axis. The 4-phenyltriazolyl groups exhibit
p–p
supramolecular stacking motif which guides the intermolecular
stacking along the b axis with the distance between the centre of
assembly of the modified cellobiose molecules. For the non-

70
J. A. Hayes et al. / Carbohydrate Research 388 (2014) 67–72
Figure 4. View of the unit cell of compound (7) showing the 21 screw axis between the two molecules in the unit cell and p–p stacking extending along the crystallographic b
axis.
reducing end of the cellobiose residue the primary hydroxyl acts as
both a hydrogen bond donor and acceptor to the primary hydroxyl
on the non-reducing end of an adjacent cellobiose residue (Fig. 2).
The 2-OH of the reducing end of the cellobiose residue donates an
intermolecular hydrogen bond to 3-OH of the non-reducing end of
an adjacent molecule, while 4-OH of the non-reducing end donates
a hydrogen bond to the 3-OH of the non-reducing end of an adja-
cent residue (Supplementary Material, Fig. 7). The water molecules
are filling voids in the lattice without hydrogen bonding between
them.
In summary, acetamidocellobiose derivative (5) and phenyl-
triazolylcellobiose derivative (7) were prepared from azide (2)
and crystallised as dihydrates. In the crystal structure of compound
(5), the cellobiose molecules are stacked upon each other with an
amide C(4) hydrogen bonding chain. In the phenyltriazolyl deriva-
tive (7), the two molecules in the unit cell are related by a 21 screw
cellobiose molecules in their crystalline forms. Both structures dis-
play hydrogen bonding motifs typical of cellodextrins, such as
intramolecular S(7) rings involving the reducing end 3-OH and
the non-reducing glucopyranose. However, the intermolecular
hydrogen bonding between cellobiose residues in the two struc-
tures is different. The success of the acetamido and phenyltriazolyl
groups in promoting stacking of the glucopyranose unit could be
further exploited by extension to cellotriose and larger cellodext-
rins, although there is likely to be increased difficulty in growing
crystals suitable for crystal structure analysis as the molecular size
increases.
1. Experimental
1.1. General methods
axis and the 4-phenyltriazolyl groups exhibit p–p stacking. Hence
All commercial reagents were purchased from Sigma–Aldrich
and were used without further purification. All solvents were
either of a HPLC grade or distilled prior to use. Column chromatog-
raphy was conducted using Merck silica gel 60, typically with a
30:1 ratio of silica to sample. Infrared spectra were recorded on a
Perkin–Elmer Paragon 1000 FT-IR spectrometer. The NMR spectra
in both structures, stacking of both the modifying groups, that is
the amide in (5) and the phenyltriazolyl group in (7), and the
cellobiose residues are observed. The intermolecular bonding
between these groups provides supramolecular stacking motifs
which assist the coordination and packing of the modified

J. A. Hayes et al. / Carbohydrate Research 388 (2014) 67–72
71
were recorded on a Bruker AVANCE 300 spectrometer at 300 MHz
for 1H NMR and 75 MHz for 13C NMR. Chemical shift values (dH and
dC) are expressed as parts per million (ppm). Two dimensional het-
eronuclear HETCOR and COSY experiments were employed for
spectral assignments. High resolution mass spectra (HRMS) were
recorded on a Waters LCT Premier LC–MS instrument in electro-
spray ionisation (ESI) positive mode using 50% MeCN–H2O
containing 0.1% HCO2H as eluant; samples were made up in MeCN.
Microwave assisted synthesis was conducted on a CEM Discover
S-Class synthesiser in conjunction with Synergy software.
was removed under vacuum and the crude solid was recrystallised
from a minimum of hot MeOH to yield a white solid (0.61 g, 83%).
IR (KBr):
m
3377 (NAH), 2959 (CAH), 1755 (CO), 1629 (NHC@O),
1371 (CH), 1234 (OAC@O) and 1042 (CAOAC) cmꢁ1
;
1H NMR
(CDCl3): d 1.98 (3H, s, NHAc), 1.99 (3H, s, OAc), 2.01 (3H, s, OAc),
2.03 (3H, s, OAc), 2.05 (3H, s, OAc), 2.10 (3H, s, OAc), 2.13 (3H, s,
OAc), 2.23 (3H, OAc), 3.66 (1H, m), 3.75 (2H, m), 4.04 (1H, dd,
3J = 12.5, 2.2 Hz), 4.13 (1H, m), 4.38 (1H, dd, 3J = 12.7, 4.4 Hz,),
4.49 (2H, m), 4.83 (1H, t, 3J = 9.6 Hz), 4.93 (1H, t, 3J = 8.7 Hz), 5.12
(2H, m), 5.26 (1H, m), 6.20 (1H, d, 3J = 9.4 Hz, H-1); 13C NMR
(CDCl3): d 19.55–19.71 (1 ꢂ NHAc, 7 ꢂ OAc), 60.58 (CH2), 60.87
(CH2), 66.76 (CH), 69.81 (CH), 70.48 (CH), 70.93 (CH), 71.10 (CH),
71.87 (CH), 73.42 (CH), 75.21 (CH), 77.07 (CH), 99.60 (C-1),
168.01 (NHAc), 168.31 (OAc), 168.39 (OAc), 169.24 (OAc), 169.22
(2 ꢂ OAc), 169.51 (OAc), 170.32 (OAc).
1.2. Synthesis
1.2.1. 1-Azido-1-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-b-
glucopyranosyl)-2,3,6-tri-O-acetyl-b- -glucopyranose (2)
1-Bromo-1-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-b- -glucopyran-
osyl)-2,3,6-tri-O-acetyl-
-glucopyranose15 1 (5.0 g, 7.16 mmol)
D-
D
D
a-
D
1.2.4. 1-Acetamido-1-deoxy-(4-O-b-D-glucopyranosyl)-b-D-
was dissolved in DMSO (35 mL) and NaN3 (1.39 g, 21.48 mmol)
was added. The resulting solution was stirred at room temperature
for 1 h after which the solution was poured into water (150 mL).
The resulting cloudy solution was stirred at room temperature
for 20 min and the precipitate collected by filtration. Recrystallisa-
tion from hot MeOH yielded the azide as a white solid (3.07 g, 65%).
glucopyranose (5)
To
acetyl-b-
a
solution of 1-acetamido-1-deoxy-4-O-(2,3,4,6-tetra-O-
-glucopyranosyl)-2,3,6-tri-O-acetyl-b- -glucopyranose 4
D
D
(2.0 g, 2.95 mmol) in dry MeOH (50 mL) was added MeOK
(41 mg, 0.59 mmol) and the solution stirred for 4 h. The solution
was neutralized with AmberlystÒ ion exchange resin (to pH 7)
and was stirred for 30 min. The resin was removed by gravity fil-
tration and the solvent removed under vacuum. The crude solid
was recrystallised from a minimum of hot MeOH to yield a white
Mp 170–175 °C (lit.15 = 182–182.5 °C); IR (KBr):
2119 (N3), 1755 (C@O), 1374 (CAH), 1241 (OAC@O) and 1059
(OACAO) cmꢁ1 1H NMR (CDCl3): d 1.91 (3H, s, OAc), 1.94 (3H, s,
m 2970 (CAH),
.
OAc), 1.95 (3H, OAc), 1.96 (3H, s, OAc), 2.00 (3H, s, OAc), 2.02
(3H, s, OAc), 2.08 (3H, s, OAc), 3.56–3.64 (2H, m, H-5, H-50), 3.72
(1H, t, 3J = 9.3 Hz, H-4), 3.96 (1H, dd, 3J = 12.0, 3.0 Hz), 4.04 (1H,
dd, 3J = 12.0, 3.0 Hz), 4.31 (1H, dd, 3J = 12.0, 3.0 Hz), 4.42-4.49
(2H, m), 4.56 (1H, d, 3J = 8.7 Hz, H-1), 4.77–4.89 (2H, m), 5.00
crystalline solid (0.84 g, 74%). Mp 155 °C; IR (KBr):
m 3414 (OAH),
2952 (CAH) and 1667 (C@O) cmꢁ1 1H NMR (D2O): d 2.06 (3H, s,
;
NHAc), 3.28–3.31 (1H, m), 3.37–3.53 (4H, m), 3.66–3.97 (7H, m),
4.50 (1H, d, 3J = 8.1 Hz), 4.96 (1H, d, 3J = 9.0 Hz, H-1); 13C NMR
(D2O): d 21.99 (NHAc), 59.68 (CH2), 60.49 (CH2), 69.36 (CH),
71.45 (CH), 73.05 (CH), 74.88 (CH), 75.37 (CH), 75.90 (CH), 76.26
(CH), 77.87 (CH), 78.98 (CH), 102.42 (C-1), 175.42 (NHAc). MS-
3
(1H, t, 3J = 9.3 Hz), 5.05 (1H, t, J = 9.3 Hz, H-40), 5.12 (1H, t,
3J = 9.3 Hz, H-3).
ESI: Found m/z, 406.1316; calcd for
C
14H25NO11Na [M+Na+],
1.2.2. 1-Amino-1-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-b-
glucopyranosyl)-2,3,6-tri-O-acetyl-b- -glucopyranose (3)
1-Azido-1-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-b- -glucopyrano-
syl)-2,3,6-tri-O-acetyl-b- -glucopyranose 2 (10.0 g, 15.12 mmol)
D
-
406.1325.
D
D
1.2.5. 1-Deoxy-1-(4-phenyl-1,2,3-triazolyl)-4-O-(2,3,4,6-tetra-O-
acetyl-b- -glucopyranosyl)-2,3,6-tetra-O-acetyl-b-
D
D
D-
was dissolved in a 9:1 mixture of MeOH: THF (200 mL) and Pd/C
(0.32 g, 0.30 mmol of active palladium) was added. The resulting
suspension was placed in a Parr pressure reactor APP 600, com-
bined with a Texol HYG 600 H2 generator and a Watlow series
945 overhead stirrer under a positive atmosphere of H2 at 200
psi. The H2 atmosphere was maintained at 200 psi and the mixture
was agitated for 16 h. The catalyst was removed by filtration on a
bed of CeliteÒ and the solvent removed under reduced pressure to
yield an off white solid in quantitative yield. Mp 195–187 °C; IR
glucopyranose (6)
1-Azido-1-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
syl)-2,3,6-tri-O-acetyl-b-D-glucopyranose (2) (1.5 g, 2.27 mmol),
CuSO4ꢀ5H2O (56.7 mg, 0.27 mmol), and sodium ascorbate
(67.3 mg, 0.34 mmol) were dissolved in DMF (20 mL) along with
phenylacetylene (0.27 mL, 2.49 mmol) and 4 drops of water. The
mixture was then subjected to microwave radiation (300 W,
30 min) at 80 °C. The resulting cloudy yellow suspension was di-
luted with CHCl3 (50 mL) and filtered through a bed of CeliteÒ.
The organic layer was thoroughly washed with water
(2 ꢂ 20 mL), brine (2 ꢂ 20 mL), and dried over MgSO4. The solvent
was removed under vacuum to yield a pale yellow solid. Recrystal-
lisation from hot MeOH yielded a white solid (1.59 g, 92%). Mp
(KBr):
m
3411, 3500 (NH2), 2955 (CH), 1746 (CO), 1379 (CH),
1228 (OAC@O) and 1035 (CAOAC) cmꢁ1
;
1H NMR (CDCl3): d 1.91
(3H, s, OAc), 1.94 (3H, s, OAc), 1.95 (3H, OAc), 1.96 (6H, 2 ꢂ OAc),
2.01 (3H, s, OAc), 2.07 (3H, s, OAc), 3.61–3.76 (2H, m), 3.92–4.04
(3H, m), 4.21–4.32 (3H, m), 4.53 (1H, t, 3J = 9.3 Hz), 4.63 (1H, t,
3J = 9.6 Hz), 4.81 (1H, d, 3J = 8.1 Hz, H-1), 4.87 (1H, t, 3J = 9.1 Hz),
5.10 (1H, t, 3J = 9.3 Hz), 5.24 (1H, t, 3J = 9.3 Hz).
266.78 °C; IR (KBr):
m
2874–3126 (CAH), 1757 (C@O), 1371
(CAH), 1231 (OAC@O) and 1070 (CAOAC) cmꢁ1
;
1H NMR (CDCl3):
d 1.88 (3H, s, OAc), 1.92 (3H, s, OAc), 1.95 (3H, s, OAc), 1.98 (6H, s,
2 ꢂ OAc), 2.04 (3H, s, OAc), 2.05 (3H, s, OAc), 3.63 (1H, ddd, 3J = 9.0,
4.8, 2.4 Hz), 3.82–3.91 (2H, m), 4.01 (1H, dd, 3J = 12.3, 2.4 Hz), 4.10
(1H, dd, 3J = 12.3, 4.8 Hz), 4.32 (1H, dd, 3J = 12.3, 4.2 Hz), 4.45 (1H,
d, 3J = 11.7 Hz), 4.51 (1H, d, 3J = 7.8 Hz), 4.89 (1H, t 3J = 9.3 Hz), 5.02
(1H, t, 3J = 9.3 Hz), 5.10 (1H, t, 3J = 9.3 Hz), 5.34 (1H, t, 3J = 9.3 Hz),
5.49 (1H, t, 3J = 9.3 Hz), 5.86 (1H, d, 3J = 9.0 Hz), 7.35–7.45 (3H,
m), 7.82 (2H, d, 3J = 7.5 Hz), 7.92 (1H, s). 13C NMR (CDCl3): d
20.22 (OAc), 20.45 (2 ꢂ OAc), 20.52 (OAc), 20.67 (2 ꢂ OAc), 20.77
(OAc), 61.58 (CH2), 61.70 (CH2), 67.76 (CH), 70.36 (CH), 71.59
(CH), 72.14 (CH), 72.43 (CH), 72.84 (CH), 75.91 (CH), 75.99 (CH),
85.61 (CH), 100.81 (C-1), 117.80 (CH@Cq), 125.88 (2 ꢂ ArCH),
128.57 (ArCq), 128.87 (ArCH), 129.9 (2 ꢂ ArCH), 148.34 (CH@Cq),
1.2.3. 1-Acetamido-1-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-b-
glucopyranosyl)-2,3,6-tri-O-acetyl-b- -glucopyranose (4)
1-Amino-1-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-b- -glucopyran-
osyl)-2,3,6-tri-O-acetyl-b- -glucopyranose 3 (0.69 g, 1.086 mmol)
D-
D
D
D
and pyridine (0.04 mL, 0.543 mmol) were added to a round bot-
tomed flask containing acetic anhydride (0.113 mL, 1.195 mmol)
and THF (15 mL). The reaction mixture was heated to reflux for
24 h and the solvent was removed under vacuum. The reaction
mixture was then diluted with dichloromethane (30 mL), washed
with satd aq NaHCO3 (2 ꢂ 20 mL), aq CuSO4ꢀ5H2O (2 ꢂ 20 mL),
water (30 mL), brine (30 mL), and dried over MgSO4. The solvent

72
J. A. Hayes et al. / Carbohydrate Research 388 (2014) 67–72
169.05 (OAc), 169.21 (OAc), 169.29 (OAc), 169.52 (OAc), 170.16
(OAc), 170.18 (OAc), 170.45 (OAc).
Thermal analysis data and PXRD patterns for compounds (5) and
(7) are provided as Supplementary data.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2014.
02.011.
1.2.6. 1-Deoxy-1-(4-phenyl-1,2,3-triazolyl)-(4-O-b-
anosyl)-b- -glucopyranose (7)
To solution of 1-deoxy-1-(4-phenyl-1,2,3-triazolyl)-4-O-
(2,3,4,6-tetra-O-acetyl-b- -glucopyranosyl)-2,3,6-tetra-O-acetyl-b-
-glucopyranose (6) (1.0 g, 1.31 mmol) in dry MeOH (25 mL) was
added MeOK (18 mg, 0.26 mmol) and the solution stirred for 4 h.
The solution was neutralized with AmberlystÒ ion exchange resin
(to pH 7) and was allowed to stir for 30 min. The resin was
removed by gravity filtration and the solvent removed under vac-
uum. The crude solid was recrystallised from a minimum of hot
MeOH to yield an off white crystalline solid (0.58 g; 95%) Mp
D-glucopyr-
D
a
D
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D
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m
3385 (OH), 2961 (CH), 1672 (C@C), 1231 and
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1.3. Solid state characterisation
Crystals of compounds (5) and (7) suitable for single-crystal X-
ray diffraction were grown by slow evaporation of aqueous meth-
anol solutions. Single-crystal X-ray diffraction measurements for
compound (5) were collected on a Bruker SMART X2S diffractom-
eter as previously described.21 A Rigaku FR-E+ diffractometer fitted
with VariMax HF optics to give monochromatized Mo Ka radiation
was used for compound (7) following previously described proce-
dures.22 Calculations for (5) were made using the APEX2 v2009.
3-0 software23 incorporating the SHELX suite of programs for
structure solution and refinement.24 Calculations for (7) were
made using CrystalClear-SM Expert 2.0 r13 software.25 The struc-
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diagrams were prepared using Mercury.27
Acknowledgments
This publication has emanated from research conducted with
the financial support of Science Foundation Ireland under Grant
Numbers 07/SRC/B1158, 05/PICA/B802/EC07 and 12/RC/2275,
IRCSET (PD/2012/2652) and the UCC 2012 Strategic Research Fund.
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Perez, S. Biopolymers 1979, 18, 2369–2374.
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J.; Kelly, D. M.; Jennings, W. B.; Ni Dhubhghaill, O. M.; Moynihan, H. A.;
Maguire, A. R.; Lawrence, S. E. J. Appl. Crystallogr. 2011, 44, 213–215.
22. Coles, S. J.; Gale, P. A. Chem. Sci. 2012, 3, 683–689.
23. APEX2 v2009.3-0; Bruker AXS; Madison, WI, 2009.
24. Sheldrick, G. M. Acta Crystallogr. A 2008, 64, 112–122.
25. CrystalClear-SM Expert 2.0 r13 program suite, Rigaku Corporation, Japan, 2011.
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27. Macrae, C. F.; Bruno, I. J.; Chisholm, J. A.; Edginton, P. R.; McCabe, P.; Pidcock, E.;
Rodriguez-Monge, L.; Taylor, R.; van de Streek, J.; Wood, P. A. J. Appl. Crystallogr.
2008, 41, 466–470.
Supplementary data
The crystallographic data on compounds (5) and (7) (dihy-
drates) have been deposited with the Cambridge Crystallographic
Data Centre, CCDC numbers 976571 and 976572. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Full data
on all hydrogen bonds are given in the Supplementary data.