Structural studies of a novel bioactive benzophenone derivative: (4-Chloro-2-hydroxy-phenyl)-phenyl-methanone

Article abstract of DOI:10.1080/15421406.2015.1069470

The title compound (4-Chloro-2-hydroxy-phenyl)-phenyl-methanone was synthesized and the product obtained was characterized by spectroscopic techniques, and finally the structure was confirmed by X-ray diffraction studies. The compound crystallizes in the orthorhombic crystal system with the space group Pbca with unit cell parameters, a = 14.0359(5) ?, b = 6.8084(3) ?, c = 23.1097(8) ?, and Z = 4. The structure exhibits an intramolecular hydrogen bond which closes an S(6) ring. No directional interactions beyond the van der Waals packing contacts were identified in the crystal structure.

Full text of DOI:10.1080/15421406.2015.1069470

Molecular Crystals and Liquid Crystals
ISSN: 1542-1406 (Print) 1563-5287 (Online) Journal homepage: http://www.tandfonline.com/loi/gmcl20
Structural studies of a novel bioactive
benzophenone derivative: (4-Chloro-2-hydroxy-
phenyl)-phenyl-methanone
Zabiulla, S. Naveen, A. Bushra Begum, Shaukath Ara Khanum & N. K.
Lokanath
To cite this article: Zabiulla, S. Naveen, A. Bushra Begum, Shaukath Ara Khanum & N. K.
Lokanath (2016) Structural studies of a novel bioactive benzophenone derivative: (4-Chloro-2-
hydroxy-phenyl)-phenyl-methanone, Molecular Crystals and Liquid Crystals, 625:1, 233-237
To link to this article: http://dx.doi.org/10.1080/15421406.2015.1069470
Published online: 19 Feb 2016.
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Date: 20 February 2016, At: 15:37

MOL. CRYST. LIQ. CRYST.
, VOL. , –

http://dx.doi.org/./..
Structural studies of a novel bioactive benzophenone
derivative: (-Chloro--hydroxy-phenyl)-phenyl-methanone
a
b
a
a
c
Zabiulla , S. Naveen , A. Bushra Begum , Shaukath Ara Khanum , and N. K. Lokanath
a
b
Department of Chemistry, Yuvaraja’s College, Mysuru, India; Institution of Excellence, Vijnana Bhavana,
c
Manasagangotri, University of Mysore, Mysuru, India; Department of Studies in Physics, Manasagangotri,
University of Mysore, Mysuru, India
ABSTRACT
KEYWORDS
The title compound (4-Chloro-2-hydroxy-phenyl)-phenyl-methanone
was synthesized and the product obtained was characterized by spec-
troscopic techniques, and finally the structure was confirmed by X-ray
diffraction studies. The compound crystallizes in the orthorhombic crys-
tal system with the space group Pbca with unit cell parameters, a =
Benzophenones; crystal
structure; hydrogen bond
˚
˚
˚
1
4.0359(5) A, b = 6.8084(3) A, c = 23.1097(8) A, and Z = 4. The struc-
ture exhibits an intramolecular hydrogen bond which closes an S(6) ring.
No directional interactions beyond the van der Waals packing contacts
were identified in the crystal structure.
1
. Introduction
Benzophenones are a class of compounds obtained from natural sources [1] or by synthetic
methods [2]. Benzophenone and substituted benzophenone derivatives have been found to
possess diverse biological activities such as antimicrobial [3], anti-inflammatory [4], antiox-
idant [5], and anticancer [6] activities. These are of great importance fundamentally due to
their diverse biological and chemical properties. Benzophenones exhibit significant antitu-
mor activity both in vitro and in vivo [7]. In addition, synthetic benzophenones, such as
2-aminobenzophenone [8] and dihydroxy-4-methoxy benzophenone [9] have proven to be
antimitotic and anticancer agents respectively. Recently, para-methoxy-substituted benzophe-
nones were evaluated as p38a inhibitors with high efficacy and selectivity (IC50: 14 nM) [10].
Amino- and methoxy-substituted benzophenones have been reported to be potent cytotoxic
agents against a panel of human cancer cell lines, including multi-drug resistant cell lines
[
11]. Analogs of benzophenone exhibit a selective toxicity for proliferating endothelial cells
by induction of apoptosis [12], and polyprenylated benzophenone derivatives are also able to
induce caspasemediated apoptosis [13]. In view of their broad spectrum of medicinal prop-
erties and as a part of our ongoing work on benzophenone derivatives [14], the title com-
pound was synthesized. The compound obtained was characterized spectroscopically, and
finally confirmed by X-ray diffraction studies.
CONTACT N. K. Lokanath
versity of Mysore, Mysuru  , India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gmcl.
 Taylor & Francis Group, LLC
lokanath@physics.uni-mysore.ac.in
Department of Studies in Physics, Manasagangotri, Uni-
©

2
34
ZABIULLA ET AL.
Figure . Schematic diagram of the title compound.
2
2
. Experimental
.1. Preparation of (4-Chloro-2-hydroxy-phenyl)-phenyl-methanone
The starting material benzoate was synthesized by benzoylation of p-chloro phenol with ben-
zoyl chlorides (1:1) in the presence of 10% sodium hydroxide solution. The reaction mass
was stirred for 2–3 hr at 0°C. After the completion of reaction, the oily product was extracted
with ether layer and dried over anhydrous sodium sulphate, and the solvent was evaporated
under pressure. (4-Chloro-2-hydroxy-phenyl)-phenyl-methanone were synthesized by the
Fries rearrangement. Benzoate (0.001 mol) and aluminium chloride (0.002 mol) were blended
and the mixture was heated to 150–170°C under without-solvent condition for about 2–3 hr.
Then the reaction mixture was cooled to 0°C and quenched with 6 N hydrochloric acid in the
presence of ice water. The reaction mixture was stirred for about 2–3 hr, filtered, and the solid
obtained was recrystallized with methanol by the slow evaporation method to obtain green
colored crystals. A schematic diagram of the molecule is shown in Fig. 1; yield: 80%; m.p.:
2
72–274°C.
Table . Crystal data and structure refinement table.
Parameter
Value
CCDC deposit No.
Empirical formula
Formula weight

C H Cl F N O S


   
. Da
() K
Temperature
Wavelength
Crystal system, space group
. A˚
Orthorhombic, P  
  
Unit cell dimensions
a = .() A˚
b = .() A˚
c = .() A˚

Volume
.() A˚
–
Z, calculated density
Absorption coefficient
F()
Crystal size
Theta (θ) range for data collection
, . mg m
. mm

–
. × . × . mm
o
. to .°
Limiting indices
−ࣘ h ࣘ , − ࣘ k ࣘ, −ࣘ l ࣘ
Reflections collected/unique
Refinement method
Data/restraints/parameters
/ [R(int) = .]

Full-matrix least-squares on F
//
.

Goodness-of-fit on F
Final R indices [I > σ(I)]
R indices (all data)
Largest diff. peak and hole
R = ., wR = .
R = ., wR = .
–
. and −. e. A˚

MOL. CRYST. LIQ. CRYST.
235
˚
Table . Bond lengths (A).
Atoms
Length
Atoms
Length
C-C
C-C
C-C
C-C
C-C
C-C
C-C
C-O
C-C
.()
.()
.()
.()
.()
.()
.()
.()
.()
C-C
C-C
C-O
C-C
C-C
C-C
C-C
C-Cl
.()
.()
.()
.()
.()
.()
.()
.()
–
1
–1
Infrared (IR) (KBr) νmax (cm ): 1635 (C=O), 3520–3640 cm (OH)
1H NMR (400 MHz) (CDCl3): δ 6.7–7.8 (m, 8H, Ar–H), 9.1 (bs, 1H, OH).
Liquid chromatography–mass spectrometry (LC-MS) m/z: 232 (M+1, 233), 266 (100), 154.5 (57),
11.5 (50).
1
Anal. Calcd. for C13H9ClO2 C, 67.11; H, 3.90; Cl, 15.24%. Found: C, 67.05; H, 3.83; Cl, 15.20%
2.2. Crystal Structure Determination
A green color, rectangle-shaped single crystal of dimensions 0.3 × 0.27 × 0.25 mm of the title
compound was chosen for an X-ray diffraction study. The X-ray intensity data were collected
at a temperature of 296 K on a Bruker Proteum2 CCD diffractometer equipped with an X-
˚
ray generator operating at 45 kV and 10 mA, using CuK radiation of wavelength 1.54178 A.
α
Data were collected for 24 frames per set with different settings of ϕ (0° and 90°), keeping the
scan width of 0.5°, exposure time of 2 s, the sample-to-detector distance of 45.10 mm, and 2θ
value at 46.6°. A complete data set was processed using SAINT PLUS [15]. The structure was
2
solved by direct methods and refined by full-matrix least squares method on F using SHELXS
and SHELXL programs [16]. All the non-hydrogen atoms were revealed in the first difference
˚
Fourier map itself. All the hydrogen atoms were positioned geometrically (C–H = 0.93 A, O–
˚
H = 0.82 A) and refined using a riding model with U (H) = 1.2 U and 1.5 U (O). After
iso
eq
eq
several cycles of refinement, the final difference Fourier map showed peaks of no chemical
significance and the residuals saturated to 0.0326. The geometrical calculations were carried
out using the program PLATON [17]. The molecular and packing diagrams were generated
using the software MERCURY [18]. The details of the crystal structure and data refinement
Table . Bond angles (º).
Atoms
Angle (°)
Atoms
Angle (°)
C-C-C
C-C-C
C-C-C
C-C-C
C-C-C
C-C-C
C-C-C
C-C-C
O-C-C
O-C-C
C-C-C
C-C-C
.()
.()
.()
.()
.()
.()
.()
.()
.()
.()
.()
.()
C-C-C
C-C-C
.()
.()
.()
.()
.()
.()
.()
.()
.()
.()
.()
O-C-C
O-C-C
C-C-C
C-C-C
C-C-C
C-C-C
C-C-Cl
C-C-Cl
C-C-C

236
ZABIULLA ET AL.
Figure . ORTEP of the molecule with thermal ellipsoids drawn at % probability.
are given in Table 1. The list of bond lengths and bond angles of non-hydrogen atoms are given
in Tables 2 and 3 respectively. Figure 2 represents the ORTEP of the molecule with thermal
ellipsoids drawn at 50% probability.
3
. Results and discussion
The molecule is non-planar. The two phenyl rings are bridged via a carbonyl group. The
bond lengths and bond angles are normal and the molecular conformation is characterized
o
by a dihedral angle of 56.42(10) between the mean planes of two aromatic rings, and is
o
greater than the corresponding value of 51.98(11) reported for (4-Chlorophenyl)(2-hydroxy-
5
-methylphenyl)-methanone [19]. The rotation of aromatic rings is characterized by the tor-
sion angles relative to the carbonyl plane. Another indicator of conformation are the values of
Figure . Packing diagram of the molecule when viewed down along the b-axis.

MOL. CRYST. LIQ. CRYST.
237
o
o
the torsion angles C4-C3-C9-O10 = 8.0(3) and C16-C11-C9-C10 = 47.1(3) . For benzophe-
o
nones, these torsion angles take the same sign and are each reported to be 30 in energy-
minimized benzophenone. The carbonyl O atom of the benzoyl group lies nearly on the
o
hydroxychlorophenyl ring plane, as indicated by the torsion angle value of 8.0(3) for C4-C3-
C9-O10, and this value is comparable with the value reported earlier [19]. This small torsion
angle is due to the intramolecular hydrogen bonding between the hydroxy group and the car-
o
bonyl moiety and is very small compared with the reported value of 30 . The molecular con-
formation is stabilized by a strong intramolecular O–H …O hydrogen bonding between the
hydroxy group and the carbonyl moiety. The intra-molecular hydrogen bond O8–H8 …O10
o
˚
has a length of 1.85 A and an angle of 145 , which closes to form a S(6) ring. No directional
interactions beyond the van der Waals packing contacts were identified in the crystal struc-
ture. The molecules exhibit layered stacking when viewed down along the b-axis (Fig. 3).
Acknowledgments
The authors are grateful to the Institution of Excellence, Vijnana Bhavana, University of Mysore, India,
for providing the single-crystal X-ray diffractometer facility.
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