Crystal structures of two 4-phenylbenzophenones

Article abstract of DOI:10.1134/S0022476613040185

Two 4-phenylbenzophenones (I) and (II) are synthesized via Friedel-Crafts reactions. There are four crystallographically independent molecules with different conformations in the crystal structure of [1,1′-biphenyl]-4- yl(2-chlorophenyl)methanone (I). Crystals are orthorhombic, Pca2₁, C₁₉H₁₃ClO, a = 13.699(3) A, b = 8.9385(17) A, c = 46.836(9) A; V = 5735(2) A³, Z = 16, d _x = 1.356 g/cm³. Torsion angles between the biphenyl rings are between 28.5 and 30.8. Several C-H.O and C-H.Cl hydrogen bonds and weak π-π stacking contacts consolidate the crystal. Crystals of [1,1′-biphenyl]-4- yl(3-methoxyphenyl)methanone (II) are orthorhombic, Pbca, C₂₀H ₁₆O₂, a = 7.8179(15) A, b = 16.003(3) A, c = 23.345(5) A; V = 2920.7(10) A³, Z = 8, d _x = 1.311 g/cm³. The torsion angle between the biphenyl rings is 28.1 and C-H.O hydrogen bonds are observed in compound (II).

Full text of DOI:10.1134/S0022476613040185

Journal of Structural Chemistry. Vol. 54, No. 4, pp. 779-786, 2013
Original Russian Text Copyright © 2013 by Shi-Jie Zhang, Hai Xiang, Guo-Wu Rao, Wei-Xiao Hu
CRYSTAL STRUCTURES OF TWO 4-PHENYLBENZOPHENONES
1 2
Shi-Jie Zhang, Hai Xiang, Guo-Wu Rao,
3
©
UDC 548.73:548.737
3
and Wei-Xiao Hu
Two 4-phenylbenzophenones (I) and (II) are synthesized via Friedel–Crafts reactions. There are four
crystallographically independent molecules with different conformations in the crystal structure of [1,1′-
biphenyl]-4-yl(2-chlorophenyl)methanone (I). Crystals are orthorhombic, Pca2 , C19
1
H
13ClO, a =
3 3
3.699(3) Å, b = 8.9385(17) Å, c = 46.836(9) Å; V = 5735(2) Å , Z = 16, d = 1.356 g/cm . Torsion angles
1
x
between the biphenyl rings are between 28.5° and 30.8°. Several C–H…O and C–H…Cl hydrogen bonds
and weak π–π stacking contacts consolidate the crystal. Crystals of [1,1′-biphenyl]-4-yl(3-
16 2
methoxyphenyl)methanone (II) are orthorhombic, Pbca, C20H O , a = 7.8179(15) Å, b = 16.003(3) Å,
3 3
c = 23.345(5) Å; V = 2920.7(10) Å , Z = 8, d = 1.311 g/cm . The torsion angle between the biphenyl rings
x
is 28.1° and C–H…O hydrogen bonds are observed in compound (II).
DOI: 10.1134/S0022476613040185
Keywords: 4-phenylbenzophenone, [1,1′-biphenyl]-4-yl(2-chlorophenyl)methanone, [1,1′-biphenyl]-4-yl(3-
methoxyphenyl)methanone, crystal structure, single crystal XRD, torsion angle, hydrogen bond, π–π contact.
INTRODUCTION
Biphenyl is a challenging molecule from the structural point of view because its conformations in crystals, gas and
other condensed phases can differ substantially. In the crystalline state at room temperature, biphenyl owns a coplanar
conformation [1]. In the gas phase, Almenningen et al. found by electron diffraction that the equilibrium torsion angle
between the two phenyl planes was 44.4± 1.2° [2]. However, in solution, twisted conformations depend largely on the nature
of the solvent and the temperature [3], and for a biphenyl melt the dihedral angle was 32± 4° [4]. These torsion angles of
biphenyl are driven by the π-conjugation of phenyl rings, electron exchange, and steric repulsion between the adjacent hydrogen
atoms in ortho positions [5]. Furthermore, the debate for nonplanarity is still ongoing with the viewpoint that an unfavorable
lengthening of the central C–C bond might cause a hydrogen-hydrogen interaction once the planes become more coplanar [6].
Substituted biphenyls can be used as functional materials and the biphenyl moiety is also a part of many compounds
possessing potential biological activities. It is believed that degrees of the torsion angles play a critical role in bioactivities.
Among imidazolylmethylbenzophenones, biphenyl-4-yl-(3-imidazol-1-ylmethylphenyl)methanone was found to be the most
potent cytochrome P450 aromatase (CYP19) inhibitor with an IC50 value of 5.3 nM, comparable to currently marketed drugs.
Docking stimulations showed that the twisted biphenyl rings could establish interactions in a homology-built aromatase
model (PDB 1TQA), such as π–π interactions with His475 and His480 or hydrophobic contacts with Ala223 and Ala226 [7].
1
2
Graduate School, Zhejiang Chinese Medical University, Hangzhou, P. R. China; medchem@zcmu.edu.cn. College
3
of Bioengineering, Zhejiang Chinese Medical University, Hangzhou, P. R. China. College of Pharmaceutical Science,
Zhejiang University of Technology, Hangzhou, P. R. China. The text was submitted by the authors in English. Zhurnal
Strukturnoi Khimii, Vol. 54, No. 4, pp. 733-740, July-August, 2013. Original article submitted February 17, 2012.
0022-4766/13/5404-0779
779

X-ray cocrystals of peroxisome proliferators-activated receptor gamma (PPARγ) inhibitors revealed that compounds with a
twisted 4-phenylbenzophenone tail part could extend deeper into the pocket entrance of the protein (PDB 3GBK) and make
extensive hydrophobic contacts with the surrounding residues [8]. Moreover, in search for one subtype multidrug resistance-
associated protein (ABCC2/MRP2) inhibitor, it was concluded that in various biphenyl-substituted heterocycles, the degrees
of twisting between the two phenyl rings are crucial to the inhibition of ABCC2/MRP2 [9].
Studies on the conformations of substituted biphenyls have long attracted the attention of researchers who have
made considerable efforts on theoretical and experimental investigations. Numerous theoretical studies have been performed
on substituted biphenyls [10], several of which were accompanied by experimental studies [11, 12]. Recently, Grineva has
analyzed the conformations of 139 para-X–C H –C H –para-Y molecules and intermolecular contacts formed by these
6
4
6
4
molecules in 95 homo- and heteromolecular crystals based on the data of the Cambridge Structural Database (CSD) [13]. The
para-substituents X and Y were limited to H, halogens, CH , OH, COOH, NH , NO , and CN moieties.
3 2 2
Herein, we synthesized two 4-phenylbenzophenones (I) and (II) via Friedel–Crafts reactions, as shown in Scheme 1,
and discussed their crystallographic properties.
Scheme 1
EXPERIMENTAL
Melting points were taken on an X-4 apparatus and are uncorrected. Infrared spectra (IR) were obtained on a
Thermo Nicolet Avatar 370 FT–IR spectrophotometer. Ultraviolet spectra (UV) were obtained on a Jasco V-550 UV/VIS
1
spectrophotometer. H NMR spectra were recorded on a Brucker AVANCE III spectrometer operating at 500 MHz.
[1,1′-Biphenyl]-4-yl(2-chlorophenyl)methanone (I) was obtained as follows [14, 15]. To a solution of biphenyl
(9.3 g, 60 mmol) and anhydrous aluminum chloride (9.6 g, 72 mmol) in dry carbon disulfide (40 ml) ortho-chlorobenzoyl
chloride (11.6 g, 66 mmol) in carbon disulfide (20 ml) was added dropwise at room temperature. The reaction mixture was
refluxed for 8 h and poured onto ice-water containing 10% hydrochloric acid. The mixture was extracted by carbon disulfide
and the organic layer was washed by water and brine, and dried over anhydrous sodium sulfate. The crude product was
purified by recrystallization in 95% ethanol to give colorless solid, 14.0 g (yield: 79.7%); T : 94-97°С (T : 94°С [16]); IR
m
m
–1 1
KBr)/cm : 3063, 1670, 1603, 1295, 931, 744; H NMR (CDCl , 500 MHz)/ppm: 7.89 (d, J = 8.5 Hz, 2H, Ar), 7.69 (d,
(
3
J = 8.5 Hz, 2H, Ar), 7.63 (d, J = 7.0 Hz, 2H, Ar), 7.49-7.43 (m, 4H, Ar), 7.42-7.37 (m, 3H, Ar).
1,1′-Biphenyl]-4-yl(3-methoxyphenyl)methanone (II) was obtained in the same manner, with the corresponding
meta-methoxybenzoyl chloride (11.3 g, 66 mmol), as colorless solid, 14.6 g (yield: 67.6%); T : 99-105°С (T : 105-106°С
14]); IR (KBr)/cm : 1658, 1592, 1278, 778; 1H NMR (CDCl , 500 MHz)/ppm: 7.80 (d, J = 9.0 Hz, 2H, Ar), 7.70 (d,
[
m
m
–1
[
3
J = 9.0 Hz, 2H, Ar), 7.65 (d, J = 7.5 Hz, 2H, Ar), 7.48 (t, J = 7.5 Hz, 2H, Ar), 7.42-7.38 (m, 4H, Ar), 7.15-7.13 (m, 1H, Ar),
.87 (s, 3H, OCH3).
Single crystals of compounds (I) and (II) suitable for the XRD analysis were grown from ethanol by slow
3
evaporation at room temperature. The crystal data were collected on a Rigaku AFC10/Saturn 724+ diffractometer equipped
with graphite monochromated MoK (λ = 0.71073 Å) radiation by ϕ–ω scanning in a range to 2θ = 55° using the
α
2
CrystalClear program [17]. The structures were solved by direct methods and refined on F by full-matrix least-squares
techniques with SHELXS97 and SHELXL97 [18]. All of the hydrogen atoms were located in theoretical positions and
3
refined isotropically. The C–H distances were 0.95 Å for aromatic C atoms and 0.98 Å for the sp C atom. Crystallographic
data, main experiment characteristics, and refinement parameters for the structures of (I) and (II) are given in Table 1.
780

TABLE 1. Crystallographic Data, Main Experiment Characteristics, and Refinement Parameters for Structures I and II
Compound No.
Gross formula
Molecular weight
Crystal system
Space group
I
II
C
19
H
13ClO
20 16 2
C H O
292.74
Orthorhombic
Pca2
288.33
Orthorhombic
1
Pbca
a, b, c, Å
13.699(3), 8.9385(17), 46.836(9)
7.8178(15), 16.003(3), 23.345(5)
3
V, Å
5735(2)
16
2920.7(10)
8
Z
3
d
x
, g/cm
T, K
Size, mm
Color/shape
1.356
1.311
133(2)
103(2)
0.55×0.37×0.12
Colorless/platelet
0.26
0.40×0.37×0.37
Colorless/block
0.08
–1
μ, cm
Reflections meas./indep.
Reflections with [I > 2σ(I )]
49265/12983
10971
21095/3353
2790
R
int
0.086
0.038
Refined parameters
Final R indices
GOOF
758
200
R
1
= 0.070, wR
1.00
818747
2
= 0.176
R
1
= 0.050, wR
1.00
818748
2
= 0.125
CCDC deposit No.
CIF files containing complete information on the studied structures were deposited with CCDC, deposition number
18747 and 818748, and are freely available upon request from the following web site: www.ccdc.cam.ac.uk/data_request/cif.
8
RESULTS AND DISCUSSION
As shown in Table 2, the bond lengths and angles in compounds (I) and (II) are within the normal range and in good
agreement with the values reported for some analogous structures, and the lengths of bonds joining two phenyl rings C(11)–
C(14) are in a range of 1.478(6) Å to 1.496(5) Å, quite close to the values of similar structures and to the standard value for a
single bond length between trigonally linked C atoms [19, 20]. The three internal ring bond angles, C(9)–C(8)–C(13), C(10)–
C(11)–C(12) and C(15)–C(14)–C(19), are generally smaller than the ideal angle of 120°, but similar to those found in the
related compounds [20]. In both compounds the carbonyl moieties (C(1)/C(7)/C(8)/O(1)) adopt a planar triangle geometry.
There are four crystallographically independent molecules (A, B, C, and D) with slightly different conformations in the
crystal structure of (I) (Fig. 1) and the C–Cl distances are between 1.732(5) Å and 1.753(5) Å in four independent molecules.
In the crystal structure of (I), each ring is almost planar with the maximum deviation of 0.0258 Å. The dihedral angles
between the aromatic rings A (C1–C6), B (C8–C13), and C (C14–C19) in four independent molecules in the asymetric unit
are not the same. In the molecule A, the ortho-chlorophenyl group is inclined at a dihedral angle of 110.5° to the adjacent
phenyl group of biphenyl. And the two biphenyl rings are not coplanar, twisted with a dihedral angle of 30.7°. In the
molecule B, the dihedral angles are A/B = 68.0°, B/C = 28.8°; in the molecule C, the dihedral angles are A/B = 71.9°,
B/C = 30.8°; and in the molecule D, the dihedral angles are A/B = 68.2°, B/C = 28.5° respectively. In the crystal structure of
compound (II), each ring is almost planar with the maximum deviation of 0.0121 (2) Å (Fig. 2). The dihedral angles of the A
(C1–C6), B (C8–C13), and C (C14–C19) rings are: A/B = 46.0°, B/C = 28.1°. These torsion angles between benzene rings
are also presented in Table 2.
In the crystal of (I), eleven kinds of hydrogen bonds exist among the phenyl, carbonyl, and chloro groups, which can
be classified into seven types according to symmetry positions (Fig. 3). Details of all C–H…O and C–H…Cl hydrogen bond
781

TABLE 2. Main Bond Lengths d (Å), Bond Angles ω (deg) and Torsion Angles ϕ (deg) in Compounds I and II
I
Lengths, angles
II
A
B
C
D
C(1)–C(7)
C(7)–C(8)
1.515(6)
1.496(5)
1.219(5)
1.492(5)
1.732(5)
—
1.505(6)
1.501(5)
1.229(5)
1.478(6)
1.741(5)
—
1.499(6)
1.503(6)
1.216(5)
1.481(5)
1.753(5)
—
1.500(6)
1.487(5)
1.220(5)
1.496(5)
1.740(5)
—
1.501(2)
1.497(2)
1.221(2)
1.487(2)
—
C(7)–O(1)
C(11)–C(14)
C(2)–Cl(1)
C(3)–O(2)
1.370(2)
1.426(2)
120.7(1)
119.6(1)
119.8(1)
118.8(1)
118.0(1)
117.8(1)
27.2(2)
46.0(2)
28.1(2)
O(2)–C(20)
—
—
—
—
C(1)–C(7)–C(8)
C(1)–C(7)–O(1)
C(8)–C(7)–O(1)
C(9)–C(8)–C(13)
C(10)–C(11)–C(12)
C(15)–C(14)–C(19)
C(10)–C(11)–C(14)–C(15)
ring A/ring B
117.2(3)
121.7(4)
121.0(4)
119.2(4)
118.6(4)
118.4(4)
29.5(6)
110.5(2)
30.7(2)
119.5(4)
119.1(4)
121.1(4)
120.2(4)
117.1(4)
118.0(4)
28.3(6)
68.0(2)
28.8(2)
116.1(4)
122.3(4)
121.6(4)
119.8(4)
118.3(4)
117.8(4)
30.8(6)
71.9(2)
30.8(2)
120.5(4)
118.6(4)
120.7(4)
117.8(4)
118.8(4)
117.9(4)
28.0(6)
68.2(2)
28.5(2)
ring B/ring C
Fig. 1. Structure of compound (I) with atoms shown as ellipsoids of thermal vibrations with a probability of 0.3.
lengths and angles are given in Table 3. The C…O distances of the C–H…O hydrogen bonds are in the range of 3.242-
3.745 Å, the H…O distances are in the range of 2.63-2.84 Å, and the bond angles of them range from 121° to 169°. These
hydrogen bonds not only link the molecules into a hydrogen bonding network, but also play very important roles in the
formation, stability, and crystallization of compound (I).
782

Fig. 2. Structure of compound (II) with atoms shown as
ellipsoids of thermal vibrations with a probability of 0.3.
Fig. 3. Hydrogen-bonding in compound (I) with atoms shown as ellipsoids of thermal vibrations with a
probability of 0.1 for clarity, and hydrogen bonds are indicated by dashed lines.
TABLE 3. Hydrogen Bond Geometry in Compound I (Å, deg)
D–H…A
D–H
H…A
D…A
∠DHA
i
C(6A)–H(6A)…O(1C)
0.95
0.95
0.95
0.95
0.95
0.95
0.95
0.95
0.95
0.95
0.95
2.84
2.64
2.69
2.81
2.65
2.63
2.70
2.82
3.00
2.91
2.96
3.566
3.578
3.483
3.738
3.242
3.562
3.486
3.745
3.638
3.817
3.872
134
169
141
167
121
169
141
166
126
160
161
C(15A)–H(15A)…O(1B)
i
C(17A)–H(17A)…O(1B)
ii
C(15B)–H(15B)…O(1B)
C(5C)–H(5C)…O(1A)
iii
C(15C)–H(15C)…O(1D)
iv
C(17C)–H(17C)…O(1D)
i
C(19D)–H(19D)…O(1D)
v
C(6A)–H(6A)…Cl(1A)
i
C(12A)–H(12A)…Cl(1A)
vi
C(12C)–H(12C)…Cl(1C)
i
Symmetry codes: 1/2+x, 1–y, z; –1/2+x, 2–y, z; 1–x, 1–y, –1/2+z; 3/2–x, –1+y, –1/2+z; 1/2+x, 2–y, z; 1/2+x, –y, z.
ii
iii
iv
v
vi
783

Fig. 4. π–π Stacking contacts in compound (I) with atoms shown as ellipsoids of thermal vibrations with a
probability of 0.3.
Fig. 5. Hydrogen-bonding in compound (II) with atoms shown as ellipsoids of thermal vibrations with a
probability of 0.3, and hydrogen bonds are indicated by dashed lines
TABLE 4. Parameters of the π–π Contacts in Compound I (Å, deg)
Cg(i)…Cg(j)
d(Cg…Cg)
α
β
γ
Cg(i)_p
Cg(j)_p
ii
Cg(3A)…Cg(1B)
4.116
4.039
4.180
27.73
0.72
15.52
18.77
40.66
39.75
19.17
16.85
3.164
3.815
4.000
3.966
3.824
3.171
Cg(3B)…Cg(3D)
vii
Cg(1D)…Cg(3C)
27.38
Cg(3A), Cg(1B), Cg(3B), Cg(3D), Cg(1D) and Cg(3C) are the centroids of the C(14A)–C(19A), C(1B)–C(6B),
C(14B)–C(19B), C(14D)–C(19D), C(1D)–C(6D) and C(14C)–C(19C) rings respectively.
ii vii
Symmetry codes: –1/2+x, 2–y, z; 3/2–x, y, –1+z.
In addition, aromatic π–π stacking contacts are observed between a part of molecules in the crystal of (I) (Fig. 4),
and the centroid-centroid distances are slightly more than 4.0 Å, as listed in Table 4. These π–π stacking contacts further
consolidate the crystal packings.
The crystal structure of (II) exhibits four kinds of intermolecular C–H…O hydrogen bonds (Fig. 5). Details of the
ii
hydrogen bonding geometry are listed in Table 5. One ether O(2) [symmetry code: 1/2–x, 1–y, 1/2+z] atom is involved in a
784

TABLE 5. Hydrogen Bond Geometry in Compound II (Å, deg)
D–H…A
D–H
H…A
D…A
∠DHA
i
C(17)–H(17)…O(1)
0.95
0.95
0.95
0.98
2.59
2.68
2.91
2.61
3.253
3.376
3.491
3.443
127
131
121
142
ii
C(18)–H(18)…O(2)
C(19)–H(19)…O(2)
ii
iii
C(20)–H(20B)…O(2)
i
Symmetry code: x, 1/2–y, 1/2+z; 1/2–x, 1–y, 1/2+z; 1–x, 1–y, –z.
ii
iii
Fig. 6. The molecular packing for (II) viewed down the b axis, showing the layers parallel to the bc plane.
Hydrogen bonds are omitted for clarity.
Fig. 7. IR and UV absorption spectra for crystalline compounds (I) and (II).
weak bifurcated hydrogen bond to two aromatic H atoms, H(18) and H(19), while the aromatic H(17) atom forms a shorter
i
hydrogen bond with carbonyl O(1) [symmetry code: x, 1/2–y, 1/2+z]. Besides, methyl C(20) also participates in the C–
iii
H…O [symmetry code: 1–x, 1–y, –z] hydrogen bonding. The molecules are packed as infinite layers parallel to the bc plane
with an interplanar separation at 3.9 Å and no hydrogen bonding or obvious π–π stacking contacts are observed between the
layers (Fig. 6).
The IR and UV absorption spectra of compounds (I) and (II) are presented in Fig. 7. The carbonyl absorption bands
–1 –1
lie at 1670 cm and 1658 cm for compounds (I) and (II) respectively in the IR spectra. From UV spectra, compound (I)
EtOH
exhibits two peaks at λmax 205 nm (εmax 42000) and 295 nm (εmax 24000), along with a shoulder peak at around 216-
EtOH
2
18 nm, while compound (II) displays three peaks at λmax 205 nm (εmax 45000), 221 nm (εmax 31000), and 292 nm (εmax
785

25000) respectively. A red shift of an absorption maximum in compound (II) moves towards longer wavelength at 221 nm
than in compound (I) with a shoulder peak at around 216-218 nm. On the whole, the absorption intensity in compound (II)
increases with an increase in the extent of the chromophore, indicating a hyperchromic effect compared with compound (I). It
may be produced by the presence of a stronger auxochrome of methoxyl group substituted to biphenyl.
Shi-Jie Zhang acknowledges the financial support from Zhejiang Chinese Medical University (Grant No. 2011ZY26).
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