The synthesis and crystal determination of 3-hydroxy-4-(4-methoxyphenyl)-5- (2-nitrophenyl)furan-2(5H)-one

Article abstract of DOI:10.1007/s10870-010-9946-9

The title compound, C₁₇H₁₃NO₆, was synthesized and structurally characterized by elemental analysis, MS, ¹H NMR and single crystal X-ray diffraction. It crystallizes in monoclinic system space group C 2/c with a = 27.981(6) A, b = 12.996(3) A, c = 8.0900(16) A, β = 91.06(3)°, V = 2941.4(10) A³, Z = 8, R ₁ = 0.0675, wR ₂ = 0.1626, and T = 298(2) K. The X-ray structure determination revealed that the center furanone ring is nearly coplanar with p-methoxybenzene ring and forms a dihedral angle of 87.2(1)° with the nitrobenzene ring. O-H...O Intermolecular hydrogen bonds link pairs of molecules into centrosymmetric dimers, making a graph set motif of R ₂ ² (10). The dimers are further assembled into a chain of edge-fused R ₄ ⁴ (34) rings running along the [001] direction. The final three-dimensional supramolecular architecture is stabilized by weak π-π interactions. Graphical Abstract: The dimers were assembled into a chain of edge-fused R ₄ ⁴ (34) rings running along the [001] direction and a co-chain is formed with an "x" pattern of the cross section.

Full text of DOI:10.1007/s10870-010-9946-9

J Chem Crystallogr (2011) 41:649–653
DOI 10.1007/s10870-010-9946-9
ORIGINAL PAPER
The Synthesis and Crystal Determination of 3-Hydroxy-
4-(4-methoxyphenyl)-5-(2-nitrophenyl)furan-2(5H)-one
•
Zhu-Ping Xiao Zhi-Yun Peng Zhu-Xiang Liu
•
•
•
Li-Hua Chen Hai-Liang Zhu
Received: 4 August 2010 / Accepted: 30 December 2010 / Published online: 13 January 2011
Ó Springer Science+Business Media, LLC 2011
Abstract The title compound, C17H13NO6, was synthe-
sized and structurally characterized by elemental analysis,
MS, 1H NMR and single crystal X-ray diffraction. It
crystallizes in monoclinic system space group C 2/c with
Introduction
Vitamin C, one of the most potent naturally occurring
antioxidants, plays an important part in the prevention of a
large number of chronic diseases [1]. 3-Hydroxyfuran-
2-one is a lipophilic analogue of vitamin C, showing better
lipophilicity and chemical stability. We therefore focused
our efforts to design and synthesize 3-hydroxyfuran-2-ones
for biological activity screen. Cotelle reported that 4-aryl-
3-hydroxyfuran-2-one is a good inhibitor of HIV-1 integr-
ase [2]. On the other hand, Bailly and Weber reported that
4,5-diaryl-3-hydroxy-2(5H)-furanone show excellent anti-
oxidative and anti-inflammatory activities [3, 4]. In the
course of our work on screening hydroxy-2(5H)-furanones
as antibacterial, we synthesized the title compound and
herein reported its crystal structure.
˚
˚
a = 27.981(6) A, b = 12.996(3) A, c = 8.0900(16) A,
˚
3
˚
b = 91.06(3)°, V = 2941.4(10) A , Z = 8, R1 = 0.0675,
wR2 = 0.1626, and T = 298(2) K. The X-ray structure
determination revealed that the center furanone ring is
nearly coplanar with p-methoxybenzene ring and forms
a dihedral angle of 87.2(1)° with the nitrobenzene ring.
O–HꢀꢀꢀO Intermolecular hydrogen bonds link pairs of
molecules into centrosymmetric dimers, making a graph set
motif of R22(10). The dimers are further assembled into a
chain of edge-fused R44(34) rings running along the [001]
direction. The final three-dimensional supramolecular
architecture is stabilized by weak p–p interactions.
Keywords Synthesis ꢀ Crystal structure ꢀ
4,5-Diphenylfuran-2(5H)-one
Experimental Section
Reagents and Techniques
2-Hydroxy-3-(4-methoxyphenyl)acrylic acid and 1,5-diaza-
bicyclo[5.4.0]undecene (reagent grade) were purchased
from Aldrich (U.S.A) and the other chemicals were pur-
chased from Sinopharm Chemical Reagent Co., Ltd
(China). Melting points (uncorrected) were determined on
a XT4 MP apparatus (Taike Corp., Beijing, China). EI
mass spectra were obtained on a Waters GCT mass spec-
Z.-P. Xiao (&) ꢀ Z.-Y. Peng ꢀ Z.-X. Liu ꢀ L.-H. Chen ꢀ
H.-L. Zhu
School of Chemistry & Chemical Engineering,
Jishou University, Jishou 416000, People’s Republic of China
e-mail: xiaozhuping2005@163.com
1
trometer, and H NMR spectra were recorded on a Bruker
AV-300 spectrometer at 25 °C with TMS and solvent
signals allotted as internal standards. Chemical shifts were
reported in ppm (d). Elemental analyses were performed on
a CHN-O-Rapid instrument and were within 0.4% of the
theoretical values.
H.-L. Zhu (&)
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing
University, Nanjing 210093, People’s Republic of China
e-mail: zhuhl@nju.edu.cn
123

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J Chem Crystallogr (2011) 41:649–653
Synthesis of 3-Hydroxy-4-(4-methoxyphenyl)-
Table 1 Crystal data and experimental crystallographic details
5-(2-nitrophenyl)furan-2(5H)-one
Empirical formula
Formula weight
Temperature (K)
C17H13NO6
327.28
The pyruvic acid (1.94 g, 10 mmol), 2-hydroxy-3-
(4-methoxyphenyl)acrylic acid, was dissolved in dry DMF
(50 mL, dried over 4A molecular sieves) at 0 °C.
1,5-diazabicyclo[5.4.0]undecene (DBU, 1.60 mL, 10.7 mmol)
and methyl iodide (3.0 mL, 60 mmol) were successively
added and the solution was stirred at 0 °C for 3 h and then
overnight at room temperature. The solution was poured
into a mixture of AcOEt (20 mL) and 1 M HCl (60 mL).
The organic layer was separated and the aqueous layer was
extracted four times with AcOEt (30 mL). The combined
organic layers were washed with H2O (20 mL) and dried
over MgSO4. Evaporation of the volatiles in vacuo affor-
ded the methyl pyruvate, which was used without further
purification. 1H NMR (DMSO-d6): 3.76 (s, 3H); 3.79
(s, 3H); 6.38 (s, 1H); 6.92(d, J = 8.8 Hz, 2H); 7.71
(d, J = 8.8 Hz, 2H); 8.95 (s, 1H).
298(2)
˚
Wavelength (A)
0.71073
Monoclinic
C 2/c
Crystal system
Space group
Cell dimensions
˚
a (A)
27.981(6)
˚
b (A)
12.996(3)
˚
c (A)
8.0900(16)
a (8)
b (8)
c (8)
90
91.06(3)
90
3
˚
Volume(A )
2941.4(10)
Z
8
Density (calculated) (Mg/m3)
Absorption coefficient (mm-1
F000
1.478
)
0.114
1360
0.80 mL of DBU (5.35 mmol) was added under stirring
to a cold (0 °C) solution of a mixture of the methyl pyru-
vate (1.1 g, 5 mmol) and 2-nitrobenzaldehyde (0.76 g,
5 mmol) in dry DMF (24 mL, dried over 4A molecular
sieves). The mixture was stirred for 4 h at 0 °C and then
poured into a mixture of AcOEt (10 mL) and HCl 1 M
(50 mL). The organic layer was separated and the aqueous
layer was extracted with AcOEt. The organic layers were
combined, washed with water, dried over Na2SO4 and
evaporated in vacuo. The oily residue was then purified by
column chromatography on silica gel. The fraction was
partially evaporated and furnished colorless blocks of (I),
3-hydroxy-4-(4-methoxyphenyl)-5-(2-nitrophenyl)furan-
2(5H)-one, suitable for single crystal structure determina-
tion. Yield of 74%, mp 204–206 °C, 1H NMR (DMSO-d6):
3.75 (s, 3H); 6.91 (s, 1H); 6.95(d, J = 9.0 Hz, 2H); 7.36
(dd, J = 5.8 Hz, J = 3.3 Hz, 1H); 7.53(d, J = 8.9 Hz,
2H); 7.67 (dd, J = 5.7 Hz, J = 3.6 Hz, 1H); 8.06 (dd,
J = 5.8 Hz, J = 3.6 Hz, 1H); 11.00 (s, 1H); EIMS m/z 327
(M?). Anal. Calcd for C17H13NO6: C, 62.39; H, 4.00; N,
4.28; Found: C, 62.44; H, 3.99; N, 4.25.
Crystal size
0.2 mm 9 0.1 mm 9 0.1 mm
1.46–25.18°
-33 B h B 33
0 B k B 15
0 B l B 9
h range for data collection
Index ranges
Reflections collected/Unique
reflections
2707/2652
Rint
0.0303
Refinement method
Full-matrix least-squares on
F2
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r(I)]
R indices (all data)
2652/1/217
1.071
R1 = 0.0675, wR2 = 0.1271
R1 = 0.1626, wR2 = 0.1958
0.235/-0.236
-3
)
˚
Largest diff. peak and hole (eA
thermal parameters in Table 2. H atoms were positioned
geometrically and refined as riding atoms, with C–H of
˚
0.93 A for aromatic H atoms, 0.96 A for CH3 groups, 0.98 A
˚
˚
˚
for CH groups and O–H of 0.82 A, Uiso(H) values were set at
X-ray Structure Determination of I
1.2 times Ueq(C) for aromatic H atoms and CH, 1.5 times
Ueq(C) for CH3 and 1.5 times Ueq(O) for O–H groups.
X-ray diffraction data were collected using a Bruker SMART
APEX CCD diffractometer with graphite-monochromated
˚
Mo-Ka radiation (k = 0.71073 A) at room temperature. A
Results and Discussion
crystal with dimensions 0.2 mm 9 0.1 mm 9 0.1 mm was
used. Data having theta less than or equal to 25° were inte-
gratedandthestructurewassolvedbythe direct methodusing
the SHELXS-97 program [5], which refined by the full-
matrix least-squares method using the SHELXL-97 program
[5]. Crystal data and experimental details are listed in
Table 1, fractional coordinates and equivalent isotropic
The title compound (I), 3-hydroxy-4-(4-methoxyphenyl)-
5-(2-nitrophenyl)furan-2(5H)-one, crystallizes in the
monoclinic space group C 2/c and the structure of (I) with the
corresponding atomic numbering scheme is shown in Fig. 1.
The bond lengths and angles of the center unsaturated
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J Chem Crystallogr (2011) 41:649–653
651
˚
Table 2 Atomic coordinates and equivalent isotropic displacement
2
parameters (A )
Table 3 Selected bond lengths (A) and bond angles (°) of Compound I
˚
Bond
Dist.
x
y
z
U(eq)
C(5)–C(8)
C(9)–O(4)
C(10)–O(3)
C(11)–C(8)
C(13)–N(1)
O(6)–N(1)
C(8)–C(9)
C(10)–O(4)
C(10)–C(11)
C(11)–O(2)
O(5)–N(1)
1.448(5)
1.454(4)
1.215(5)
1.338(5)
1.500(5)
1.188(4)
1.519(5)
1.357(5)
1.436(6)
1.363(4)
1.225(4)
C1
0.92366(19)
0.89694(14)
0.86326(15)
0.86743(14)
0.90569(13)
0.94058(14)
0.93575(15)
0.90993(12)
0.87465(13)
0.93250(15)
0.94215(13)
0.82543(13)
0.78078(14)
0.73843(15)
0.73354(16)
0.77578(19)
0.81915(16)
0.78123(13)
0.88819(11)
0.98134(10)
0.95401(11)
0.89231(9)
0.6932(4)
0.5194(3)
0.4555(3)
0.3505(3)
0.3042(3)
0.3717(3)
0.4763(3)
0.1934(3)
0.1195(3)
0.0274(3)
0.1348(3)
0.1251(3)
0.1339(3)
0.1339(3)
0.1264(3)
0.1159(3)
0.1169(3)
0.1439(3)
0.6216(2)
0.1681(2)
0.1977(7)
0.0913(18)
0.0524(10)
0.0574(11)
0.0574(12)
0.0460(10)
0.0580(12)
0.0633(12)
0.0442(9)
C2
0.2370(5)
0.3039(5)
0.2915(5)
0.2115(5)
0.1515(6)
0.1601(5)
0.1991(4)
0.2761(4)
0.1464(6)
0.1232(5)
0.2048(5)
0.2887(5)
0.2144(6)
0.0417(5)
-0.0478(6)
0.0323(5)
0.4734(4)
0.2518(4)
0.0411(4)
0.1004(4)
0.2363(4)
0.5390(4)
0.5467(4)
C3
C4
C5
C6
C7
C8
C9
0.0431(9)
C10
C11
C12
C13
C14
C15
C16
C17
N1
0.0630(12)
0.0502(11)
0.0443(10)
0.0438(9)
Angle
(°)
C(5)–C(8)–C(9)
C(9)–C(8)–C(11)
O(6)–N(1)–C(13)
O(5)–N(1)–O(6)
C(5)–C(8)–C(11)
C(8)–C(9)–C(12)
O(5)–C(13)–N(1)
123.0(3)
106.1(3)
120.9(3)
124.0(4)
130.8(4)
114.5(3)
115.1(4)
0.0572(12)
0.0564(11)
0.0674(13)
0.0541(11)
0.0493(9)
O1
0.0756(10)
0.0718(10)
0.0784(11)
0.0604(8)
O2
O3
-0.0483(2)
0.0175(2)
0.1265(3)
0.1703(3)
O4
˚
1.338(5) and 1.363(4) A respectively, which are close to
those of typical enol-lactone [7, 8].
O5
0.74294(11)
0.81632(12)
0.0749(10)
0.0761(10)
O6
The enol-lactone motif and p-methoxybenzene ring are
˚
nearly coplanar with the mean deviation of 0.0272 A. In
comparison with C5–C8–C9 angle (123.1(3)°) (Table 3),
the mildly increased C5–C8–C11 angle (130.9(3)°) may
result from the coplanar atoms (H16 and O2) increasing
their steric strain. This was supported by the other reported
analogues [6, 7, 9]. In those compounds, the bigger the
dihedral angle between enol-lactone motif and the attached
benzene ring is, the smaller the above mentioned angle is.
The nitro group is tilted out of the mean plane that it
attached by 18.0(2)°, which is significantly higher than that
observed in the other nitrobenzenes [10, 11]. The increase
in the dihedral angle may be attributed to the presence of
the C4–H4ꢀꢀꢀO6 hydrogen bond represented by a graph-set
motif of S(9), which increases the torsion angle of C12–
C13–N1–O6 (19.1(5)°) (Fig. 1). The tiltation of nitro group
is therefore disrupted the conjugation with its attached
benzene ring, and elongate the bond length of C13–N1
˚
˚
from about 1.46 A [10, 11] to 1.500(5) A. The pendent aryl
ring (C12–C17) is almost vertical to the enol-lactone ring
with the dihedral angle of 87.2(1)°.
Fig. 1 Molecular structure of compound (I). Displacement ellipsoids
are drawn at the 30% probability level. Dashed lines indicate
hydrogen bonds
In (I), there is a single O–HꢀꢀꢀO hydrogen bond utilizing
the enolic hydroxyl group as the donor (Table 4), and this
links pairs of molecules into centrosymmetric dimers
characterized by a graph-set motif of R22(10) (Fig. 2). In the
lactone ring are within the ranges reported for analogues [6]
(Table 2). C8–C11–O2 portion shows clear enol group
character with C8–C11 and C11–O2 bond lengths of
123

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J Chem Crystallogr (2011) 41:649–653
˚
Table 4 Hydrogen-bond geometry (A, °)
D–HꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–HꢀꢀꢀA
O2–H2AꢀꢀꢀO3
C4–H4ꢀꢀꢀO6
0.82
0.93
0.93
0.98
0.93
0.82
0.93
2.59
2.60
2.38
2.11
2.28
1.89
2.57
2.956(4)
3.450(5)
3.022(5)
2.832(5)
2.628(6)
2.662(4)
3.453(6)
109
152
126
129
101
157
159
C6–H6ꢀꢀꢀO2
C9–H9ꢀꢀꢀO6
C14–H14ꢀꢀꢀO5
O2–H2AꢀꢀꢀO3i
C16–H16ꢀꢀꢀO5ii
Symmetry transformations used to generate equivalent atoms: i =
-x ? 2, -y, -z; ii = x, y, z - 1
Fig. 3 Part of the crystal structure of (I), showing the formation of
the co-chain. Solid dashed line indicate hydrogen bonds. For the sake
of clarity, the H atoms not involved in the hydrogen bonds have been
omitted
Fig. 2 Part of the crystal structure of (I), showing the formation of a
hydrogen bonded dimer and R44 motif built from paired O–HꢀꢀꢀO and
C–HꢀꢀꢀO hydrogen bonds (dashed lines). For the sake of clarity, the H
atoms not involved in the hydrogen bonds have been omitted
dimers packing along c-axis, the p-methoxyphenylenol-
lactone motifs of the molecules at (x, y, z) and (-x ? 2,
-y, -z) are in lines (the least square line through all atoms
of the p-methoxyphenylenol-lactone motif) alternatively
ꢀ
running along the [233] and ½233ꢁ directions, which lie
ꢀ
parallel to the ð011Þ plane. However, the pendent o-nitro-
phenyl rings are strictly parallel, with an interplanar
˚
spacing of 2.502(4) A. A relatively weak C16–H16ꢀꢀꢀO5
interactions connect the dimers via interaction of one
nitrophenyl ring with another, forming a R44(34) ring
(Fig. 2). The combination of these motifs generates a chain
of edge-fused rings running along the [001] direction, with
R44(34) rings centered at (0, 0, n/2), where n represents an
integer. The dimers along the other direction, alternatively
presented in this chain, generate another chain (Fig. 3). A
co-chain is therefore formed with an ‘‘x’’ pattern of the
cross section.
In the structure of (I), weak p–p interactions were
found between nitrobenzene rings at (x, y, z) and those at
(-x ? 1/2, -y ? 1/2, -z ? 1), with minimum centroid
˚
separations of 4.111(3) A (Fig. 4). These weak intermo-
lecular contacts consequently link the above mentioned
co-chains into a three dimensional network.
Fig. 4 Packing diagram of compound (I) viewing along c-axis, Solid
dashed lines indicate p–p interactions
123

J Chem Crystallogr (2011) 41:649–653
653
`
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`
Pommery J, Henichart JP, Cotelle P (2008) Eur J Med Chem
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CCDC deposit number of CCDC 787202 for I contain the
supplementary crystallographic data for this paper. These
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lographic Data Centre(CCDC), 12 Union Road, Cambridge
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