Synthesis and structural characterization of N-2,3-dimethyl-5-oxo-1-phenyl- 1H-pyrazol-4-yl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide

Article abstract of DOI:10.14233/ajchem.2013.12174

Present compound N-2,3-dimethyl-5-oxo-1-phenyl-1H-pyrazol-4-yl-exo-7-oxa- bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide (C₁₉H₁₇N ₃O₄, M_r = 351.36) was synthesized and characterized by elemental analysis, ¹H NMR spectra, IR spectra and single crystal X-ray diffraction. The crystal belongs to orthorhombic, space group P212121, with a = 6.4582(8), b = 15.8179(14), c = 16.2269(15) ?, β = 90°, V = 1657.7(3) ?³, Z = 4, D_c = 1.408 g/cm³, λ = 0.71073 ?, μ(MoK_α) = 0.101 mm^-1, F₍₀₀₀₎ = 736. The final refinement gave R = 0.0326, wR(F²) = 0.0723 for 1,702 observed reflections with I > 2σ (I). The structure of the title compound comprises a racemic mixture of chiral molecules containing four stereogenic centres. X-Ray diffraction analysis reveals that the cyclohexane ring tends towards a boat conformation. The dihedral angle between the dihydropyrazole ring and the pyrrolidine ring and the aromatic ring is 82.0(1) and 57.3(1)°, respectively. The crystal structure is stabilized by N-H···O, C- H···O, C-H···N and N-H···N hydrogen bonds.

Full text of DOI:10.14233/ajchem.2013.12174

Asian Journal of Chemistry; Vol. 25, No. 2 (2013), 685-687
http://dx.doi.org/10.14233/ajchem.2013.12174
Synthesis and Structural Characterization of N-2,3-Dimethyl-5-oxo-1-
phenyl-1H-pyrazol-4-yl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide
*
ZU-PEI LIANG and JIAN LI
Department of Chemistry and Chemical Engineering, Weifang University, Weifang 261061, P.R. China
*Corresponding author: Tel: +86 536 8877561; E-mail: lzpwfu@163.com
(Received: 7 June 2011;
Accepted: 13 August 2012)
AJC-11957
Present compound N-2,3-dimethyl-5-oxo-1-phenyl-1H-pyrazol-4-yl-exo-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide (C19H17N3O4,
Mr = 351.36) was synthesized and characterized by elemental analysis, 1H NMR spectra, IR spectra and single crystal X-ray diffraction.
The crystal belongs to orthorhombic, space group P212121, with a = 6.4582(8), b = 15.8179(14), c = 16.2269(15) Å, β = 90º, V =
1657.7(3) Å3, Z = 4, Dc = 1.408 g/cm3, λ = 0.71073 Å, µ(MoKα) = 0.101 mm-1, F(000) = 736. The final refinement gave R = 0.0326, wR(F2)
= 0.0723 for 1,702 observed reflections with I > 2σ(I). The structure of the title compound comprises a racemic mixture of chiral
molecules containing four stereogenic centres. X-Ray diffraction analysis reveals that the cyclohexane ring tends towards a boat
conformation. The dihedral angle between the dihydropyrazole ring and the pyrrolidine ring and the aromatic ring is 82.0(1) and 57.3(1)º,
respectively. The crystal structure is stabilized by N-H···O, C-H···O, C-H···N and N-H···N hydrogen bonds.
Key Words: N-2,3-Dimethyl-5-oxo-1-phenyl-1H-pyrazol-4-yl-exo-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide, Synthesis,
Structural characterization.
analyzer. Furan, maleic anhydride and o-aminobenzoic acid
were purchased from Weifang Runze (China). All other
chemicals used in this work were of analytical grade.
Synthesis of the title compound: 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 precipitate 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 impurities and then the filtrate was left for crysta-
llization 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
synthesized4,5. 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, the synthesis, molecular
structure and antibacterial activities of the title compound are
reported.
Anal. calcd. (%) for C19H17N3O4: C 64.95, H 4.84, N 11.96.
EXPERIMENTAL
Found (%): C 64.82, H 4.91, N 11.88. Selected IR (KBr, νmax
,
cm-1): 3057 (Ar-H), 2936 (-C-H), 1770, 1653 (C=O), 1600
Infrared absorption spectra were obtained from a Nicolet
NEXUS 670 FT-IR spectrometer in KBr discs and were reported
in cm-1 units. 1H NMR spectra were determined on a Bruker
DRX-400 NMR spectrometer with TMS as internal standard
in DMSO-d6. Carbon, nitrogen and hydrogen analyses were
performed on an Elemental Analysensteme GmbH Vario EL
1
(C=C), 1562 (C=N), 1194 (C-O-C), 719 (=C-H). H NMR
(DMSO-d6, ppm) δ: 7.23 (m, 2H, ArH), 6.78 (m, 1H, ArH),
6.72 (d, 2H, ArH), 5.84 (d, 2H, C6H, C7H), 4.67 (m, 2H, C5H,
C8H), 3.10 (d, 2H, C3H, C4H), 2.51 (s, 3H, C14H), 1.74 (s, 3H,
C12H).

686 Liang et al.
Asian J. Chem.
O
O
Data collection and structure determination: The single
H2N
crystal X-ray data of title compound was collected on a Bruker
SMART diffractometer. The reflection data were measured at
298(2) K, using a graphite monochromator MoKα (λ = 0.71073 Å)
radiation with an ω-2θ scan mode. The total reflections were
7614 with 1702 independent ones (Rint = 0.0352), of which
237 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.
methanol
refluxed
O
O
+
N
N
O
O
N
N
N
O
The structure was solved by direct methods using
SHELXS-9710 program. The positions of the H atoms bonded
to C atoms were calculated (C-H distance 0.96 Å) and refined
using a riding model. The H atom displacement parameters
were restricted tobe 1.2 Ueq or 1.5 Ueq (methyl C) of the parent
atom. The contributions of these hydrogen atoms were included
in the structurefactor calculations. The atomic scattering factors
and anomalous dispersion corrections were taken from Interna-
tional Table for X-ray crystallography11. The final least-square
cycle gave R = 0.0326 and ωR = 0.0723 (w = 1/[σ2(Fo2) +
(0.0378P)2 + 0.0856P], where P = (Fo2 + 2Fc2)/3). S = 1.175,
(∆/σ)max = 0.000, (∆ρ)min = -0.150 and (∆ρ)max = 0.136 e/Å3.
CIF file containing complete information on the studied
structure was deposited with CCDC, deposition number
780542 and is freely available upon request from the following
web site: www.ccdc.cam.ac.uk/data_request/cif
O
O
Scheme-II: Synthesis of the title compound
Fig. 1. Molecular structure of the title compound
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.
O
O
THF
Room temp.
O
O
+
O
O
rt
O
O
Scheme-I: Synthesis of exo-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-
dicarboxylic anhydride
The condensation reaction between exo-7-oxa-bicyclo-
[2,2,1]hept-5-ene-2,3-dicarboxylic anhydride and 4-amino-
1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one proceeded
smoothly in methanol at room temperature for 1 h and refluxed
temperature for 1 h, respectively, 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 4-amino-1,2-dihydro-2,3-dimethyl-1-phenyl-
pyrazol-5-one in a ratio of 1:1.
The molecular structures with the atom-numbering
scheme are shown in Fig. 1 and the crystal packing of the
compound is depicted in Fig. 2. The selected bond distances
and angles are listed in Table-1.
The structure of the title compound, C19H17N3O4, comp-
rises a racemic mixture of chiral molecules containing four
Fig. 2. Crystal packing of the title compound
stereogenic centres. As seen from Fig. 1, the cyclohexane ring
tends towards a boat conformation and the tetrahydrofuran
ring and the dihydrofuran ring adopt envelope conformations.
The dihedral angle between the dihydropyrazole ring and the
pyrrolidine ring and the aromatic ring is 82.0(1) and 57.3(1)º,
respectively. 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 [1.502(3)-1.563
(4) Å], except C6-C7 double bond length [1.311(4) Å], are

Vol. 25, No. 2 (2013) Synthesis & Structural Characterization of Substituted Pyrazol-4-yl-7-oxa-bicyclo[2,2,1]hept-5-ene-2,3-dicarboximide 687
TABLE-1
ACKNOWLEDGEMENTS
SELECTED BOND LENGTHS (Å) AND BOND ANGLES (º)
This work was supported by Shandong Provincial Natural
Science Foundation, China (No. ZR2010BM033).
Bond
Length (Å)
1.386(3)
1.397(3)
1.423(3)
1.404(3)
1.416(3)
1.440(3)
1.350(3)
1.459(4)
1.205(3)
1.202(3)
1.441(4)
1.442(3)
1.221(3)
Bond
Angle (º)
113.0(2)
125.4(2)
121.3(2)
108.4(2)
117.0(2)
119.2(2)
108.1(2)
124.6(2)
117.2(2)
95.7(2)
N(1)-C(1)
N(1)-C(2)
N(1)-C(10)
N(2)-N(3)
N(2)-C(9)
N(2)-C(14)
N(3)-C(11)
N(3)-C(13)
O(1)-C(1)
O(2)-C(2)
O(3)-C(5)
O(3)-C(8)
O(4)-C(9)
C(1)-N(1)-C(2)
C(1)-N(1)-C(10)
C(2)-N(1)-C(10)
N(3)-N(2)-C(9)
N(3)-N(2)-C(14)
C(9)-N(2)-C(14)
C(11)-N(3)-N(2)
C(11)-N(3)-C(13)
N(2)-N(3)-C(13)
C(5)-O(3)-C(8)
O(1)-C(1)-N(1)
O(2)-C(2)-N(1)
O(4)-C(9)-N(2)
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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,
exo-4-[(4-bromophenyl)amino]-10-oxa-4-azatricyclo-
(5,2,1,02,6)dec-8-ene-3,5-dine14 and 4-(2-aminophenyl)-10-
oxa-4-azatricyclo(5,2,1,02,6)dec-8-ene-3,5-dine15. The crystal
structure is stabilized by and N-H···O, C-H···O, C-H···N and
N-H···N intermolecular hydrogen bonds (Fig. 2 and Table-2).
15. J. Li, Acta Cryst., E67, 588 (2011).
TABLE-2
HYDROGEN BOND SCHEMES (Å, º)
D-H···A
D-H
D···A
D-A
D-H···A
N2-H2A…N1
N2-H2B…O2a
C3-H3…O1b
C8-H8…O2c
C14-H14…N2d
0.86
0.86
0.98
0.93
0.98
2.498
2.275
2.480
2.594
2.610
2.820
3.131
3.232
3.369
3.484
103
174
133
141
149
Symmetry codes: (a) 1/2-x, y, 1/2+z (b) -x, -y, -1/2+z (c) -x, 1-y, 1/2+z
(d) 1/2-x, y, -1/2+z.