Synthesis and structural characterization of N-propyl-7-oxa-bicyclo[2,2,1] hept-5-ene-2,3-dicarboximide

Article abstract of DOI:10.14233/ajchem.2013.12108a

The compound N-propyl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide (C₁₁H₁₃NO₃, M_r = 207.22) was synthesized and characterized by elemental analysis, ¹H NMR spectra, IR spectra and single crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/c, with a = 9.7040(10), b = 8.9501(8), c = 15.4719(16) ?, β = 128.845 (2)°, V = 1046.58(18) ?³, Z = 4, D_c = 1.315 g/cm³, λ = 0.71073 ?, μ(MoK_α) = 0.096 mm^-1, F ₍₀₀₀₎ = 736. The final refinement gave R = 0.0434, wR(F²) = 0.0998 for 5.254 observed reflections with I > 2σ (I). The structure of this compound comprises a racemic mixture of chiral molecules containing four stereogenic centres. X-ray diffraction analysis reveals that the cyclohexene ring tends towards a boat conformation, the tetrahydrofuran ring and the dihydrofuran ring adopt envelope conformation. The plan C3/C4/C5/C8 and the plan C5/C6/C7/C8 form dihedral angles of 69.1 (2)° and 64.2 (2)°, respectively with the pyrrole ring. The crystal structure is stabilized by C-H...O hydrogen bonds.

Full text of DOI:10.14233/ajchem.2013.12108a

Asian Journal of Chemistry; Vol. 25, No. 2 (2013), 660-662
http://dx.doi.org/10.14233/ajchem.2013.12108A
Synthesis and Structural Characterization of
N-propyl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide
*
JIAN LI and ZU-PEI LIANG
Department of Chemistry and Chemical Engineering, Weifang University, Weifang 261061, P.R. China
*Corresponding author: Tel: +86 536 8877561, E-mail: zupeiliang@163.com
(Received: 23 May 2011;
Accepted: 11 August 2012)
AJC-11951
The compound N-propyl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide (C11H13NO3, Mr = 207.22) was synthesized and characterized
by elemental analysis, 1H NMR spectra, IR spectra and single crystal X-ray diffraction. The crystal belongs to monoclinic, space group
P21/c, with a = 9.7040(10), b = 8.9501(8), c = 15.4719(16) Å, β = 128.845 (2)º, V = 1046.58(18) Å3, Z = 4, Dc = 1.315 g/cm3,
λ = 0.71073 Å, µ(MoKα) = 0.096 mm-1, F(000) = 736. The final refinement gave R = 0.0434, wR(F2) = 0.0998 for 5.254 observed
reflections with I > 2σ(I). The structure of this compound comprises a racemic mixture of chiral molecules containing four stereogenic
centres. X-ray diffraction analysis reveals that the cyclohexene ring tends towards a boat conformation, the tetrahydrofuran ring and the
dihydrofuran ring adopt envelope conformation. The plan C3/C4/C5/C8 and the plan C5/C6/C7/C8 form dihedral angles of 69.1 (2)º and
64.2 (2)º, respectively with the pyrrole ring. The crystal structure is stabilized by C-H...O hydrogen bonds.
Key Words: N-propyl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide, Synthesis, Structure characterization.
Synthesis of N-propyl-7-oxa-bicyclo[2,2,1]hept-5-ene-
2,3-dicarboximide: Exo-7-oxa-bicyclo [2,2,1]hept-5-ene-2,3-
dicarboxylic anhydride was synthesised according to the
literature8.A mixture of exo-7-oxa- bicyclo[2,2,1]hept-5-ene-
2,3-dicarboxylic anhydride (0.332 g, 2 mmol) and 4-amino-
1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (0.406 g,
2 mmol) in methanol (5 mL) was stirred for 1 h at room
temperature and then refluxed for 1 h.After cooling, the preci-
pitate was filtered and dried, the title compound was obtained.
Yield: 82 %. The crude product of 20 mg was dissolved in
methanol of 10 mL. The solution was filtered to remove impu-
rities and then the filtrate was left for crystallization at room
temperature. The single crystal suitable for X-ray determination
was obtained by evaporation from the methanol solution after
6 d.
INTRODUCTION
The imide moiety is an integral structural part of various
important bioactive molecules such as fumaramidmycin,
granulatimide, isogranulatimide and rebeccamycin. These
molecules are reported to exhibit antitumor, antiinflammatory
and antimicrobial activities1-3. 7-Oxa-bicyclo[2,2,1]hept-5-
ene-2,3-dicarboxylic anhydride has been widely employed in
clinical practice, as it is less toxic and much easier to be synthe-
sized4,5. Its derivatives are also pharmacologically active6.
Furthermore, exo-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-
dicarboximide and its N-substituent compounds have recently
become an intense research topic in heterocyclic chemistry
because of their antitumor, antivirus, analgesic, sedative and
fungicidal activities7. In this paper, N-propyl-7-oxa-bicyclo-
[2,2,1]hept-5-ene-2,3-dicarboximide was synthesized and its
molecular structure was investigated by elemental analysis,
FT-IR, 1H NMR and X-ray crystallographic techniques.
Anal. calcd. (%) for C11H13NO3: C 63.77, H 6.28, N 6.76.
Found (%): C 63.72, H 6.32, N 6.74. Selected IR (KBr, νmax
,
cm-1) data: 2935 (-C-H), 1695 (C=O), 1600 (C=C), 1191 (C-
O-C), 718 (=C-H). 1H NMR (DMSO-d6, ppm) δ: 5.80 (d, 2H,
C6H, C7H), 4.67 (m, 2H, C5H, C8H), 3.51 (m, 2H, C9H), 3.09
(d, 2H, C3H, C4H), 1.60 (m, 2H, C10H), 0.97 (m, 3H, C11H).
Data collection and structure determination:A selected
crystal of the title compound was mounted on a SMART CCD
diffractometer. The reflection data were measured at 298 K,
using a graphite monochromator MoKα (λ = 0.71073 Å)
radiation with an ω-2θ scan mode. The total reflections were
EXPERIMENTAL
All the reagents were of AR grade and used without
further purification. IR spectra (4000-400 cm-1), as KBr pellets,
were recorded on a Nicolet FT-IR 510P spectrometer. 1H NMR
spectra were measured with a BrukerALP 80 nuclear magnetic
resonance spectrometer (CD3COCD3 as solvent, TMS as
internal standard).

Vol. 25, No. 2 (2013)
Synthesis and Structural Characterization of N-propyl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide 661
TABLE-1
5.254 with 1.853 independent ones (Rint = 0.0434), of which
138 were observed with I > 2σ(I). Intensities were corrected
for Lorentz and polarization effects and empirical absorption
and all data were corrected using SADABB9 program.
The structure was solved by direct methods using
SHELXS-9710 program. All the non-hydrogen atoms were
refined on F2 anisotropically by full-matrix least squares
method. All hydrogen atoms were placed in the geometrically
calculated positions. The contributions of these hydrogen
atoms were included in the structure factor calculations. The
atomic scattering factors and anomalous dispersion corrections
were taken from international table for X-ray crystallography11.
The final least-square cycle gave R = 0.0672 and ωR = 0.1169
(w = 1/[σ2(Fo2) + 0.0386P2 + 0.3785P], where, P = (Fo2 + 2Fc2)/
3). S = 1.066, (∆ρ)min = -0.164 and (∆ρ)max = 0.177 e/Å3. CIF
file containing complete information on the studied structure
was deposited with CCDC, deposition number 825618 and is
freely available upon request from the following web site:
www.ccdc.cam.ac.uk/data_request/cif.
SELECTED BOND LENGTHS (Å) AND BOND ANGLES (º)
Bond
O(1)-C(1)
O(2)-C(2)
O(3)-C(5)
O(3)-C(8)
N(1)-C(1)
N(1)-C(2)
N(1)-C(9)
C(6)-C(7)
Length (Å)
1.210(2)
1.203(2)
1.431(3)
1.436(3)
1.371(3)
1.378(3)
1.463(3)
1.305(3)
Bond
Angle (º)
95.74(15)
112.31(17)
123.31(17)
124.32(17)
124.0(2)
109.33(17)
123.9(2)
109.41(17)
C(5)-O(3)-C(8)
C(1)-N(1)-C(2)
C(1)-N(1)-C(9)
C(2)-N(1)-C(9)
O(1)-C(1)-N(1)
N(1)-C(1)-C(4)
O(2)-C(2)-N(1)
N(1)-C(2)-C(3)
RESULTS AND DISCUSSION
Furan reacts in a Diels-Alder reaction with maleic
anhydride in tetrahydrofuran at room temperature to give exo-
7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylic anhydride, as
shown in Scheme-I. The condensation reaction between exo-
7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylic anhydride
and 1-propanamine proceeded smoothly in methanol at room
temperature for 5 h and refluxed temperature for 1 h, respec-
tively, leading to the title compound in high yield, as shown in
Scheme-II. The elemental analysis, IR spectra and 1H NMR
data clearly indicated the condensation reaction of exo-7-oxa-
bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylic anhydride with
1-propanamine in a ratio of 1:1.
Fig. 1. Molecular structure with atomic numbering scheme
O
O
Fig. 2. View of crystal packing down the a-axis
TABLE-2
THF
rt
O
O
HYDROGEN BOND SCHEMES (Åo)
+
O
O
D-H…A
D-H
0.93
0.93
0.98
H…A
2.560
2.510
2.610
D-A
3.429
3.327
3.484
D-H…A
156
147
C6-H6…O2i
C7-H7…O1ii
C14-H14…N2d
O
O
Scheme-I:Synthesis of exo-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylic
149
anhydride
Symmetry codes: i) x, 1/2-y, ½ + z; ii) 1 + x, 1/2-y,1/2 + z
O
O
Fig. 1, the cyclohexene ring tends towards a boat conformation,
the tetrahydrofuran ring and the dihydrofuran ring adopt
envelope conformations. The plan C3/C4/C5/C8 and the plan
C5/C6/C7/C8 form dihedral angles of 69.1 (2) ° and 64.2 (2) °,
respectively with the essential planar pyrrole ring (maximum
deviation = 0.010 (4) for atom N1). As seen from Table-1, the
bond lengths are expected12. And they are comparable to those
in the similar compounds13,14. In 7-oxabicyclo(2,2,1)hept-5-
ene-2,3-dicarboximide group, the C-C bonds lengths [1.505
(3)-1.557 (3) Å], except C6-C7 double bond length [1.305(3)
Å], are longer than the normal single bond length. The degree
of lengthening of the C-C bonds in the title compound is in
good agreement with that of corresponding C-C bonds in N-
methyl-7-oxabicyclo(2,2,1)hept-5-ene-2,3-exo-dicarboximide13,
methanol
NH2
N
O
O
O
+
refluxed
O
O
Scheme-II: Synthesis of the N-propyl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-
dicarboximide
The selected bond distances and bond angles are listed in
Table-1.A displacement ellipsoid plot with atomic numbering
scheme is shown in Fig. 1 and a perspective view of the crystal
packing in the unit cell is shown in Fig. 2. Hydrogen bond
schemes (Å, º) are listed in Table-2.
The title compound comprises a racemic mixture of chiral
molecules containing four stereogenic centres. As seen from

662 Li et al.
Asian J. Chem.
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ACKNOWLEDGEMENTS
This work was supported by Shandong Provincial Natural
Science Foundation, China (No. ZR2010BM033).
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