Crystal structure of methyl 3-amino-2,3-dideoxy-β-d-arabino- hexopyranoside. Stabilization of the crystal lattice by a double network of N-H...O, O-H...N and O-H...O interactions

Article abstract of DOI:10.1016/j.carres.2005.06.031

The structure, conformation and configuration of methyl 3-amino-2,3-dideoxy-β-d-arabino-hexopyranoside were investigated by ¹H NMR, ¹³C NMR and IR spectroscopy, as well as by optical rotation. The crystal structure was confirmed by single-crystal X-ray crystallographic analysis at 293 K and R = 0.0434 based on 910 independent reflections. The crystal belongs to the monoclinic system, space group of P2₁ with cell dimensions a = 6.050(1) A, b = 7.284(1) A, c = 10.289(2) A, β = 104.69(3)°, D_c = 1.341 Mg cm ^-3 and V = 438.9(1) A³ for Z = 2. Furthermore, the molecule has a typical ⁴C₁ chair conformation. Hydrogen bonds between sugar molecules are responsible for stabilizing the crystal lattice.

Full text of DOI:10.1016/j.carres.2005.06.031

Carbohydrate
RESEARCH
Carbohydrate Research 340 (2005) 2201–2205
Crystal structure of methyl 3-amino-2,3-dideoxy-
b-D-arabino-hexopyranoside. Stabilization of the crystal lattice by
a double network of N–Hꢀ ꢀ ꢀO, O–Hꢀ ꢀ ꢀN and O–Hꢀ ꢀ ꢀO interactions
*
´
Aleksandra Da˛browska, Dagmara Jacewicz, Artur Sikorski and Lech Chmurzynski
Faculty of Chemistry, University of Gdan´sk, Sobieskiego 18/19, 80-952 Gdan´sk, Poland
Received 11 April 2005; accepted 10 June 2005
Available online 25 July 2005
Abstract—The structure, conformation and configuration of methyl 3-amino-2,3-dideoxy-b-D-arabino-hexopyranoside were inves-
1
tigated by H NMR, 13C NMR and IR spectroscopy, as well as by optical rotation. The crystal structure was confirmed by sin-
gle-crystal X-ray crystallographic analysis at 293 K and R = 0.0434 based on 910 independent reflections. The crystal belongs to
˚
˚
4
˚
the monoclinic system, space group of P21 with cell dimensions a = 6.050(1) A, b = 7.284(1) A, c = 10.289(2) A, b = 104.69(3)ꢀ,
Dc = 1.341 Mg cmꢁ3 and V = 438.9(1) A for Z = 2. Furthermore, the molecule has a typical C1 chair conformation. Hydrogen
bonds between sugar molecules are responsible for stabilizing the crystal lattice.
ꢁ 2005 Elsevier Ltd. All rights reserved.
3
˚
Keywords: Methyl 3-amino-2,3-dideoxy-b-D-arabino-hexopyranoside; Single-crystal X-ray structure; Conformation and configuration; Hydrogen
bonding; Weak interactions
1. Introduction
X-ray structural analysis of its b-anomer. We observe an
elaborate network of N–Hꢀ ꢀ ꢀO and O–Hꢀ ꢀ ꢀN interac-
tions that stabilize the molecules in the solid state. The
details of the structural analysis are presented herein.
Solid-state organization of carbohydrates is governed
generally by hydrogen-bonding interactions in well-
defined geometrical arrangements in the crystal lattice.1
The presence of highly directional O–Hꢀ ꢀ ꢀO hydrogen-
bonding networks is an inbuilt feature of the hydroxyl
groups abundant sugar pyranoses.2 Although there are
several crystal structure reports available on either par-
tially or fully protected derivatives of pyranosides, the
generality of noncovalent interactions responsible for
the stability of crystalline lattice sugar derivatives
remains to be understood in detail. The roles of weak
interactions are becoming increasingly important to
understand the packing forces in the crystalline lattice
of carbohydrates.
2. Experimental
2.1. Materials and methods
The synthetic methods for the prepared substances are
given in Refs. 4 and 5. TLC was carried out on Silica
Gel 60 F254 aluminum plates (E. Merck). Melting points
were determined using a Buchi 510 apparatus. Optical
¨
rotations were measured using Hilgel–Watts polarimeter
in 1-dm tubes at the D line of sodium and room temper-
ature. IR spectra were recorded as Nujol mulls with a
Bruker IFS 66 spectrophotometer. The 1H and 13C
NMR spectra were measured using a Varian Mercury
spectrometer at 400 MHz in CD3OD with Me4Si as
the internal standard. Field desorption mass spectra
(FDMS) were recorded using a Varian Matt 711
In our previous paper, we reported the crystal struc-
ture of methyl 3-amino-2,3-dideoxy-a-D-arabino-hexo-
pyranoside.3 We have performed the single-crystal
*
Corresponding author. Tel.: +48 58 345 04 04; fax: +48 58 345 04
72; e-mail: lech@chem.univ.gda.pl
0008-6215/$ - see front matter ꢁ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2005.06.031

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A. Da˛browska et al. / Carbohydrate Research 340 (2005) 2201–2205
spectrometer. Elemental analyses were conducted with a
Carlo Erba EA1108 elemental analyzer.
2.2. Preparation of single crystals for X-ray
measurements
Methyl 3-azido-2,3-dideoxy-b-D-arabino-hexopyranos-
ide4,5 (0.5 g, 2.5 mM) was dissolved in 20 mL of dry
MeOH; the reaction mixture was stirred and argon gas
was bubbled through it for 15 min. After this time, the
reaction mixture was hydrogenated at rt for 1 h with
22 mg of 10% Pd/C. Then, the catalyst was filtered off,
and the filtrate was evaporated in vacuo to give the
crude product. Approximately 0.5–1.0 wt.% of crude
product was dissolved in 2:1 mixture of n-heptane and
EtOAc (distilled) at about 50 ꢀC. The sample tube was
slowly cooled to room temperature and stored for 3–
5 days. When no crystallization was observed after this
time, the cap of the reagent tube was slightly opened
to allow slow evaporation. Single crystals were obtained
typically within two weeks. After recrystallization,
methyl 3-amino-2,3-dideoxy-b-D-arabino-hexopyrano-
side was isolated in yields of up to 85% (0.38 g); mp
Figure 1. Structure of title compound showing 50% probability
displacements for ellipsoids (H atoms as circles).
selection of the crystalÕs important geometric parameters
is given in Table 3.
20
141.5–143 ꢀC; ½aꢂD ꢁ65 (c 0.1 CH3OH); Rf 0.29
3. Results and discussion
(MeOH); IR: m [cmꢁ1] 3400, 3348, 3304 (m-NH-amine),
2968, 2940. 2917 (mOH), 2815 (m-acetal), 1591 (d-NH-
amine), 1423 (d-OCH3), 1111, 947 (m-C–O–C); 1H
NMR (CD3OD): d [ppm] 1.353 (m, 1H, J2a,2e 12.4,
J2a,3 12.4 Hz, H-2a), 2.019 (dq, 1H, J2e,3 4.8 Hz, H-2e),
2.709 (m, 1H, J3,4 9.2 Hz, H-3), 3.038 (t, 1H, J4,5
Synthesis of the title compound was carried out by the
reduction of its 3-azido precursor with methanol in the
presence of Pd/C activators to afford the desired 3-ami-
no-2,3-dideoxysugar in 85% yield. Single crystals suit-
able for analysis were obtained upon slow evaporation
of a solution of the b anomer in n-heptane–EtOAc.
The configuration and conformation of the methyl
3-amino-2,3-dideoxy-b-D-arabino-hexopyranoside were
0
9.6 Hz, H-4), 3.21 (m, 1H, J5,6 6.0, J5,6 2.4 Hz, H-5),
0
3.47 (s, 3H, OCH3), 3.675 (dd, 1H, J6,6 12.0 Hz, H-
11A), 3.856 (dd, 1H, H-11B), 4.471 (dd, 1H, J1,2a 9.6,
J1,2e 2.0 Hz, H-1); 13C NMR (CD3OD): d [ppm]
39.574 (C-2), 54.135 (C-3), 56.87 (C-8), 63.204 (C-11),
73.788 (C-4), 79.319 (C-5), 102.904 (C-1); m/z (EI) 177
(M+, 45%); Calcd for C7H15NO4: C, 47.45; H, 8.53;
N, 7.9. Found: C, 47.41; H, 8.59; N, 7.79.
1
established on the basis of H, 13C NMR and IR spec-
troscopy and optical data. It has been reported that in
1
spite of the complexity of H NMR spectra in carbohy-
drates, the peak position for the anomeric proton is of-
ten readily identified and can provide useful diagnostic
information.10 The H-1 signal of the b anomer appeared
at a lower d value (4.47 ppm) than the analogous proton
of the a anomer3 owing to the axial orientation of H-1.
Two different values of coupling constants J1,2a 9.6 Hz
and J1,2e 2.0 Hz, as well as negative value of the optical
rotation, indicated the b-configuration for the molecule.
Furthermore, the strong coupling of H-3 and axially ori-
ented H-2 (J2a,3 12.4 Hz) indicated an axial orientation
for the H-3 proton and consequently the D-arabino
structure. The values of coupling constants, J3,4–J4,5
9.2–9.6 Hz also confirmed the D-arabino structure. All
the above findings were in accordance with the predicted
4C1 conformation.
2.3. Crystal structure determination and analysis
Diffraction data were collected at room temperature
(293 K) on a KUMA KM-4 diffractometer6 with Mo
˚
Ka radiation (k = 0.71073 A) using the 2H/x scan
mode. All H atoms were placed geometrically and
˚
refined using a riding model with C–H = 0.96 A, O–
˚
˚
H = 0.82 A, N–H = 0.86 A and Uiso(H) = 1.2Ueq(C)
˚
(C–H = 0.96 A and Uiso(H) = 1.5Ueq(C) in the case of
the methyl H atoms). The crystal structure was refined
to R1 = 0.0793 (910 reflections) and R1 = 0.0434 (810
reflections with F0 > 2r(F0)) by full-matrix least-squares
method using the program SHELX-977,8 based on 110
parameters. Atom numbering scheme and molecular
packing in the crystal are illustrated in Figures 1 and
2, respectively.9 The coordinates of atoms and their iso-
tropic temperature factors are collected in Table 2, and a
Noteworthy is the influence of the type of the substi-
tuent and configuration of the sugar on the chemical
1
shifts of the H-3 protons in the H NMR spectra. A
comparison analysis of these substituents3,4 showed that
their deshielding influence on the H-3 proton increased

A. Da˛browska et al. / Carbohydrate Research 340 (2005) 2201–2205
2203
Figure 2. Molecular packing in unit cell (view along a-axis). Hydrogen bonds are drawn in dashed lines. H atoms not involved in hydrogen bonds
have been removed.
Table 1. Crystal data and structure refinement
in the following order: –NH2 in b (d 2.71), –NH2 in a (d
3.00), –N3 in b (d 3.32), –N3 in a (d 3.95). These findings
Empirical formula
C7H15NO4
are in accordance with stereoelectronic interactions that
determine H NMR spectral positions.
Formula weight
Temperature (K)
Radiation wavelength (A)
Crystal system
Space group
Unit cell dimensions
177.20
293(2)
0.71073
Monoclinic
P21
1
˚
Crystal and X-ray diffraction data are given in Table
1. The molecular structure of methyl 3-amino-2,3-dide-
oxy-b-D-arabino-hexopyranoside is shown in Figure 1.
The coordinates of atoms and their isotropic tempera-
ture factors are collected in Table 2. All bond lengths
and valence and torsion angles are in proximity of the
ideal values. Some selected values are shown in Table 3.
The title compound crystallizes in the P21 space group
and differs significantly when compared to its a ano-
mer.3 The differences are related to the structure of the
sugar unit where the intermolecular contacts are impor-
tant in the overall arrangement of molecules in their
crystal states.
˚
a (A)
6.050(1)
7.284(1)
10.289(2)
104.69(3)
438.60(13)
2
1.342
0.109
192
0.3 · 0.3 · 0.4
2.05–25.25
ꢁ7 6 h 6 7, 0 6 k 6 8,
0 6 l 6 12
910/863
[Rint = 0.0368]
100
Full-matrix least-
squares on F2
863/1/113
1.006
R1 = 0.043
wR2 = 0.120
R1 = 0.079
wR2 = 0.142
3(3)
0.13(3)
0.339 and ꢁ0.159
˚
b (A)
˚
c (A)
b (ꢀ)
3
˚
V (A )
Z
Calculated density (Mg mꢁ3
)
Absorption coefficient (mmꢁ1
F(000)
)
Crystal size (mm)
H range for data collection (ꢀ)
Limiting indices
An analysis of the C–C bond lengths within the pyra-
nose ring shows that they are in the range between 1.488
Reflections collected/unique
˚
and 1.544 A (Table 3). Amongst the bonds within the
Completeness to 2H = 50.50 (%)
Refinement method
˚
pyranose ring, exocyclic C-1–O-7 1.377(5) A is found
to be the shortest. C-5–O-6 and O-6–C-1 are 1.437(5)
˚
and 1.411(5) A, respectively. The shortening of C-1–O-7
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2r(I)]
compared to O-6–C-1 indicates a significant anomeric
effect.
The Cremer–Pople puckering parameters11,12 Q =
R indices (all data)
˚
0.566(5) A, H = 1.8(5)ꢀ and the relevant dihedral angles
are indicative of almost perfect 4C1 conformation for the
six-membered pyranoside ring (O-6–C-1–C-2–C-3–C-4–
C-5). The packing arrangements are shown in Figure 2
(view along a-axis) and Fig. 3 (view along b-axis). The
torsion angles O-6–C-5–C-11–O-12 of ꢁ67.5(4)0 and
C-4–C-5–C-11–O-12 of 53.6(5)0 indicate the gauche–
gauche orientation of the primary hydroxy group with
respect to the ring oxygen, as well as the C-4 hydroxyl
group. On the other hand, the torsion angles of O-6–
C-1–O-7–C-8 of ꢁ72.4(5)0 and C-2–C-1–O-7–C-8 of
166.2(4)0 show that the anomeric substituent has
Absolute structure parameter
Extinction coefficient
Largest diff. peak and hole (e Aꢁ3
)
gauche–trans orientation with respect to the pyranose
ring.
Data on intermolecular interactions, that is, N–
Hꢀ ꢀ ꢀO, O–Hꢀ ꢀ ꢀN and O–Hꢀ ꢀ ꢀO hydrogen bonds are
presented in Table 4. Intermolecular hydrogen bonds
˚
extend from 2.7 A for O–Hꢀ ꢀ ꢀN and O–Hꢀ ꢀ ꢀO to

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A. Da˛browska et al. / Carbohydrate Research 340 (2005) 2201–2205
Table 2. Atomic coordinates (·104) and equivalent isotropic displace-
ment parameters (A · 10 ) for non-hydrogen atoms
˚
3.1 A for N–Hꢀ ꢀ ꢀO bonds. When viewed along the a-
axis, each molecule in the crystal lattice interacts with
another symmetry-related molecule by these hydrogen
bonds. These two types of hydrogen bonds, specifically
2
3
˚
Atom
x/a
y/b
z/c
Ueq
C-1
C-2
C-3
C-4
C-5
O-6
O-7
C-8
N-9
O-10
C-11
O-12
3209(8)
4509(8)
5881(7)
4316(6)
3010(7)
1790(5)
1883(6)
1005(9)
7056(6)
5619(5)
1335(8)
ꢁ167(5)
2232(6)
1164(8)
2414(8)
3847(6)
4868(6)
3560(4)
1044(4)
1835(7)
1384(7)
5142(6)
6221(8)
5469(7)
ꢁ1237(4)
ꢁ2054(5)
ꢁ2711(4)
ꢁ3529(4)
ꢁ2638(4)
ꢁ2037(3)
ꢁ717(3)
42(1)
49(1)
45(1)
38(1)
40(1)
41(1)
55(1)
52(1)
56(1)
54(1)
53(1)
67(1)
˚
Table 4. Hydrogen-bond distances and angles with Hꢀ ꢀ ꢀA < r(A) +
a
˚
2.00 A and D–Hꢀ ꢀ ꢀA > 110ꢀ
D–Hꢀ ꢀ ꢀA
D–H
Hꢀ ꢀ ꢀA
2.55
1.93
1.92
Dꢀ ꢀ ꢀA
3.135(6)
2.736(5)
2.721(5)
D–Hꢀ ꢀ ꢀA
126
168
166
311(5)
N-9–H-8Bꢀ ꢀ ꢀO-12i
O-10–H-10Aꢀ ꢀ ꢀN-9ii
O-12–H-12Aꢀ ꢀ ꢀO-10iii
0.86
0.82
0.82
ꢁ3560(4)
ꢁ4045(3)
ꢁ3404(5)
ꢁ4509(3)
a Symmetry codes: (i) [ꢁx + 1, y ꢁ 1/2, ꢁz ꢁ 1], (ii) [ꢁx + 1, y + 1/2,
ꢁz ꢁ 1], (iii) [x ꢁ 1, y, z]. D and A denote donor and acceptor,
respectively.
Ueq is defined as one-third of the trace of the orthogonalized Uij tensor.
˚
Table 3. Selected bond lengths (A), valence and torsion angles (ꢀ)
Bond lengths
Valence angles
Torsion angles
C-1–O-7
C-1–O-6
C-1–C-2
C-2–C-3
C-3–N-9
C-3–C-4
C-4–O-10
C-4–C-5
C-5–O-6
C-5–C-11
O-7–C-8
C-11–O-12
1.377(5)
1.411(5)
1.505(6)
1.503(7)
1.465(6)
1.513(6)
1.416(5)
1.544(5)
1.437(5)
1.488(7)
1.421(5)
1.376(6)
O-7–C-1–O-6
O-6–C-1–C-2
O-7–C-1–C-2
C-1–C-2–C-3
C-2–C-3–N-9
C-3–C-4–N-9
C-2–C-3–C-4
O-10–C-4–C-3
O-10–C-4–C-5
C-3–C-4–C-5
O-6–C-5–C-11
O-6–C-5–C-4
C-4–C-5–C-11
C-1–O-6–C-5
C-1–O-7–C-8
O-12–C-11–C-5
109.2(3)
110.8(4)
109.3(4)
111.4(4)
111.4(4)
110.6(4)
109.2(4)
109.8(3)
108.6(4)
110.2(3)
108.2(3)
109.4(3)
112.8(3)
113.8(3)
113.5(3)
113.0(5)
O-7–C-1–C-2–C-3
O-6–C-1–C-2–C-3
C-1–C-2–C-3–N-9
C-1–C-2–C-3–C-4
N-9–C-3–C-4–O-10
C-2–C-3–C-4–O-10
N-9–C-3–C-4–C-5
C-2–C-3–C-4–C-5
O-10–C-4–C-5–O-6
C-3–C-4–C-5–O-6
O-10–C-4–C-5–C-11
C-3–C-4–C-5–C-11
O-7–C-1–O-6–C-5
C-2–C-1–O-6–C-5
C-11–C-5–O-6–C-1
C-4–C-5–O-6–C-1
O-6–C-1–O-7–C-8
C-2–C-1–O-7–C-8
O-6–C-5–C-11–O-12
C-4–C-5–C-11–O-12
176.7(3)
56.3(5)
ꢁ177.2(4)
ꢁ54.7(5)
ꢁ62.8(5)
174.2(4)
177.6(4)
54.6(5)
ꢁ176.4(3)
ꢁ56.1(5)
63.1(5)
ꢁ176.6(4)
ꢁ179.6(3)
ꢁ59.1(5)
ꢁ177.8(4)
59.0(5)
ꢁ72.4(5)
166.2(4)
ꢁ67.5(4)
53.6(5)
Figure 3. Molecular packing in unit cell (view along b-axis). The dashed lines represent hydrogen bonds. H atoms not involved in hydrogen bonds
have been removed.

A. Da˛browska et al. / Carbohydrate Research 340 (2005) 2201–2205
2205
N-9–H-8Bꢀ ꢀ ꢀO-12 and O-10–H-10Aꢀ ꢀ ꢀN-9, form a zig-
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12Aꢀ ꢀ ꢀO-10, forms an infinite chain connecting mole-
cules and is roughly perpendicular to the above two inter-
actions. Consequently, these hydrogen bonds form rings
between crystal layers along the b-axis in the unit cell.
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This research was supported by the Polish State Com-
mittee for Scientific Research under grants BW/8000-
5-0265-5 and DS/8231-4-0097-5.