Crystal and molecular structures of 2-(4-Chlorophenyl)-5,7- dimethoxyquinolin-4-yl phenyl bis(2-chloroethyl) phosphoramidate

Article abstract of DOI:10.1134/S0022476611050234

2-(4-Chlorophenyl)-5,7-dimethoxyquinolin-4-yl phenyl bis(2-chloroethyl) phosphoramidate is synthesized and characterized by NMR, IR and single crystal X-ray crystallography. The crystal is triclinic, P1 space group, with a = 9.5188(19) A, b = 12.856(3) A,

Full text of DOI:10.1134/S0022476611050234

Journal of Structural Chemistry. Vol. 52, No. 5, pp. 989-992, 2011
Original Russian Text Copyright © 2011 by J. W. Yuan, L. B. Qu, X. L. Chen, Z. B. Qu, and Y.C. Li
CRYSTAL AND MOLECULAR STRUCTURES OF
2-(4-CHLOROPHENYL)-5,7-DIMETHOXYQUINOLIN-
4-YL PHENYL BIS(2-CHLOROETHYL) PHOSPHORAMIDATE
1
J. W. Yuan, L. B. Qu, X. L. Chen, Z. B. Qu,
1,2
2
2
UDC 548.737:546.18
1
and Y.C. Li
2-(4-Chlorophenyl)-5,7-dimethoxyquinolin-4-yl phenyl bis(2-chloroethyl)phosphoramidate is synthesized
and characterized by NMR, IR and single crystal X-ray crystallography. The crystal is triclinic, P1 space
3
group, with a = 9.5188(19) Å, b = 12.856(3) Å, c = 13.250(3) Å, V = 1412.0(5) Å) , and Z = 2 (at
291(2) K). The crystal packing arrangement indicates that the molecule is stacked through π…π aromatic
stacking interactions.
Keywords: crystal and molecular structure, X-ray crystallography, 2-phenyl-4-quinolone,
phosphoramidate.
INTRODUCTION
In the latest years, considerable attention has been paid to the development of programs to purposefully synthesize
biologically active 2-phenyl-4-quinolones and related derivatives [1, 2]. These compounds can be used as potential
antimitotic [3], antibacterial [4], and anti-platelet agents [5] and cardiovascular protectors [6]. Moreover, phosphoramidates,
as an important component, have often been introduced to modify a wide variety of structurally diverse natural and
biologically active compounds, such as glycolipids and nucleic acids [7, 8]. The corresponding derivatives are sometimes
used as prodrugs to increase the water solubility and bio-availability of the agent [9]. Importantly, they have also been found
considerable biological interest as anticancer agents [10]. In the previous paper, the correlated phosporamidate derivatives of
2-phenyl-4-quinolones was reported by our group [11, 12]. It is known that the biological activity of a compound is related to
the geometry of its molecules and also the non-covalent bond interactions. The fine structure of one representative of 2-
phenyl-4-quinolone
derivatives
series,
2-(4-chlorophenyl)-5,7-dimethoxyquinolin-4-yl
phenyl
bis(2-chloro-
ethyl)phosphoramidate containing a phosphoramide mustard substituent, was shown in Fig. 1. It was obtained in a high yield
by the reaction of 2-phenyl-4-quinolone with phosphoramidochloridate under mild conditions. The structure of the title
compound was analyzed based on the X-ray crystallographic data for a deeper understanding of the structure of
phosphoramidate derivatives of 2-phenyl-4-quinolones.
1
Chemistry and Chemical Engineering School, Henan University of Technology, Henan Province, Zhengzhou, P. R.
2
China; qulingbo@zzu.edu.cn. Department of Chemistry, Zhengzhou University, Key Laboratory of Organic Chemistry and
Chemical Biology, Henan Province, Zhengzhou, P. R. China. The text was submitted by the authors in English. Zhurnal
Strukturnoi Khimii, Vol. 52, No. 5, pp. 1015-1018, September-October, 2011. Original article submitted January 29, 2010.
0022-4766/11/5205-0989 © 2011
989

Fig. 1. Synthesis of the title compound.
EXPERIMENTAL
Synthesis. 2-(4-Chlorophenyl)-5,7-dimethoxy-4-quinolone (0.5 g, 1.6 mmol) and phenyl bis(2-chloroethyl)
phosphoramidochloridate (0.54 g, 1.7 mmol) was dissolved in tetrahydrofuran (40 ml) and stirred at room temperature for
20 min. A mixed solution of dry triethylamine (0.25 ml, 1.7 mmol) and tetrahydrofuran (5 ml) was added dropwise to the
stirred solution. The reaction mixture was allowed to stand for 1 h before heating for 10 h to reflux. The solution was filtered,
evaporated to dryness, and the residue was purified by column chromatography on silica gel (cyclohexane: ethyl acetate, 3:1).
A 0.6 g colorless crystal was obtained, yield: 65%. m.p. 106-107°C. Found, %: C 54.28, H 4.29, N 4.72. C H Cl N O P.
27 26
3
2
5
Calculated, %: C 54.43, H 4.40, N 4.70.
1 13
NMR spectra were measured on a Bruker Avance 400 MHz spectrometer. H and C chemical shifts were
31
determined relative to internal TMS. P chemical shifts were determined relative to 85% H PO as the external standard.
3
4
1
Infrared (IR) spectra in KBr pellets were recorded on a Shimadazu IR-408 spectrometer. H NMR (CDCl ) δ: 7.89 (s, 1H,
3
4
3-H), 6.55 (d, J
4
= 1.4 Hz, 1H, 6-H), 7.10 (d, J
3
= 1.4 Hz, 1H, 8-H), 8.04 (d, J
= 8.5 Hz, 2H, 2′6′-H), 7.44 (d,
H–H
H–H
H–H
3
3
3
J
H–H
= 8.5 Hz, 2H, 3′5′-H), 3.94 (s, 6H, 5, 7-OCH ), 7.25 (d, J = 8.2 Hz, 2H, 2″6″-H), 7.33 (d, J = 8.0 Hz, 2H, 3″5″-H),
3 H–H H–H
3
13
7.17 (t,
J
= 7.6 Hz, 1H, 4″-H), 3.70–3.59 (m, 8H, NCH CH Cl). C NMR (CDCl ) δ: 157.3 (2-C), 106.6 (d,
H–H 2 2 3
3
2
= 2.7 Hz, 3-C), 155.2 (d, J = 6.7 Hz, 4-C), 156.4 (5-C), 99.7 (6-C), 161.6 (7-C), 100.9 (8-C), 153.6 (9-C), 108.2 (d,
J
J
J
C–P
C–P
C–P
C–P
3
2
= 6.8 Hz, 10-C), 137.0 (1′-C), 128.7 (2′6′-C), 128.9 (3′5′-C), 135.8 (4′-C), 55.7 (5-OCH ), 56.0 (7-OCH ), 150.4 (d,
3 3
3 2
= 7.2 Hz, 1″-C), 120.2 (d, J = 5.0 Hz, 2″6″-C), 129.9 (3″5″-C), 125.5 (4″-C), 49.4 (d, J = 4.4 Hz, NCH ), 41.7
C–P
C–P
2
31 –1
(CH Cl). P NMR (CDCl ) δ: –0.70. IR(KBr), ν(cm ): 2962, 2935, 2835 (CH , CH ), 1590 (C=N), 1210 (P=O), 1036 (P–O).
2
3
3
2
Single crystal X-ray diffraction. Crystals of X-ray quality were obtained by slow crystallization of the material
from methanol at room temperature with subsequent drying in air.
The X-ray diffraction analysis of the title compound (0.20×0.18×0.16 mm) was carried out at 291(2) K on an
R-Axis-IV diffractometer with a graphite monochromatic MoK radiation (λ = 0.71073 Å) in oscillation scan mode. The unit
α
cell dimensions were obtained with the least-squares refinements, and the structure was solved by direct methods using the
2
SHELXS-97 program [13] and refined by the full matrix least squares fitting on F with anisotropic thermal parameters for
all non-hydrogen atoms using SHELXL-97 [14]. Hydrogen atoms were generated geometrically. Molecular illustrations were
prepared using the XP package.
The crystal is colorless and triclinic; C H Cl N O P; M = 595.82; a = 9.5188(19) Å, b = 12.856(3) Å,
27 26 3 2 5
3 3
c = 13.250(3) Å; α = 110.90(3)°, β = 100.55(3)°, γ = 103.08(3)°; V = 1412.0(5) Å , d = 1.401 g/cm , Z = 2, P1 space group.
x
The scan angle is 1.72 < θ < 25.00°. A total of 4471 reflections were measured, 4471 being independent (R = 0.0000).
int
Absorption correction was introduced semi-empirically from equivalents. Final values of divergence factors are R = 0.0587
and R = 0.1509. GOOF = 1.075, extinction coefficient 0.019(2). Coordinates of atoms and structural parameters of the
w
crystal have been deposited with the Cambridge Crystal Structure Database (CCDC 680149).
990

Fig. 2. View of the molecule of the title
compound. Thermal ellipsoids are drawn
at the 30% probability level.
Fig. 3. Crystal packing of the title compound.
Thermal ellipsoids are drawn at the 30% probability
level.
RESULTS AND DISCUSSION
The X-ray structural study revealed the specific features and geometry of the title compound that was isolated as
well-shaped crystals. An overall view of the molecule is shown in Fig. 2. The P=O bond length (1.455(3) Å) in the crystal
structure is close to the normal P=O bond length found in P(O)Cl (1.45 Å) [15, 16] and is shorter than those of P(1)–O(2)
3
(1.585(2) Å) and P(1)–O(3) (1.598(2) Å). The P–N bond length (1.629(3) Å) is shorter than the typical P–N bond length
found in NaHPO NH (1.77 Å) [17].
3
2
The environment of the amine N(1) atom of the compound is approximately trigonal planar, since the C(1)–N(1)–
C(3), C(1)–N(1)–P(1), and C(3)–N(1)–P(1) angles have the values of 118.0(3)°, 120.6(3)°, and 121.0(2)° respectively with
2
average 119.9°, which indicates sp hybridization for the nitrogen atoms (deviation from the ideal value of 120° can be
caused by electronic and/or steric effects). The C(18)–C(19)–C(20)–C(21) torsion angle is 12.5(5)°, which shows that the
plane of the quinoline ring is not coplanar with the 4-chlorophenyl group. Furthermore, the C(16)–C(15)–N(2)–C(19) torsion
angle has a value of 1.3(5)°, which indicates that the quinoline ring is not absolutely planar.
In the crystal packing, as shown in Fig. 3, the adjacent molecules consisting of two enantiomers with a phosphorus
atom as a stereogenic center are stacked through π…π aromatic stacking interactions with a face-to-face distance of 3.40 Å
and a 0° angle between the quinoline rings. Interestingly, the conjugated molecular planes are arranged in a head-to-tail
fashion due to a strong “push-pull” electron system. No intramolecular and intermolecular hydrogen bonds were observed in
the crystal structure. Intermolecular π…π stacking interactions also make a considerable contribution to the supramolecular
organization of the crystal structure.
This work was supported by the Chinese National Science Foundation (No. 20472076) and the Henan Academic
Foundation of Science and Technology (No. 0512001400).
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