Synthesis and crystal structure of [5-Chloro-2-(4-nitro-benzyloxy)-phenyl]- (4-chloro-phenyl) methanone

Article abstract of DOI:10.1080/15421400903290766

The title compound, C20H13Cl2NO4, crystallizes in the monoclinic crystal system and space group P21/n with cell parameters a=9.434(2)A, b=13.167(3)A, c=15.087(4)A, β=105.289(8)°, V=1807.7(7)A3 for Z=4. The structure exhibits inter-molecular hydrogen bonds

Full text of DOI:10.1080/15421400903290766

This article was downloaded by: [University of Otago]
On: 02 January 2015, At: 22:36
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Molecular Crystals and Liquid
Crystals
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gmcl20
Synthesis and Crystal Structure
of [5-Chloro-2-(4-nitro-
benzyloxy)-phenyl]-(4-chloro-
phenyl) Methanone
S. Neetha a , T. D. Venu b , M. A. Sridhar a , J.
Shashidhara Prasad a & S. Shashikanth b
a Department of Studies in Physics , University of
Mysore , Mysore, India
b Department of Studies in Chemistry , University of
Mysore , Mysore, India
Published online: 17 Dec 2009.
To cite this article: S. Neetha , T. D. Venu , M. A. Sridhar , J. Shashidhara Prasad & S.
Shashikanth (2009) Synthesis and Crystal Structure of [5-Chloro-2-(4-nitro-benzyloxy)-
phenyl]-(4-chloro-phenyl) Methanone, Molecular Crystals and Liquid Crystals, 515:1,
151-158, DOI: 10.1080/15421400903290766
To link to this article: http://dx.doi.org/10.1080/15421400903290766
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with

primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Mol. Cryst. Liq. Cryst., Vol. 515, pp. 151–158, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400903290766
Synthesis and Crystal Structure of [5-Chloro-2-(4-nitro-
benzyloxy)-phenyl]-(4-chloro-phenyl) Methanone
S. Neetha1, T. D. Venu2, M. A. Sridhar1,
J. Shashidhara Prasad1, and S. Shashikanth2
1Department of Studies in Physics, University of Mysore, Mysore, India
2Department of Studies in Chemistry, University of Mysore,
Mysore, India
The title compound, C20H13Cl2NO4, crystallizes in the monoclinic crystal system
˚
˚
and space group P21=n with cell parameters a ¼ 9.434(2) A, b ¼ 13.167(3) A,
3
ꢀ
˚
˚
c ¼ 15.087(4) A, b ¼ 105.289(8) , V ¼ 1807.7(7) A for Z ¼ 4. The structure exhibits
inter-molecular hydrogen bonds of the type C-H ꢁ ꢁ ꢁ O.
Keywords: benzophenone; crystal structure; hydrogen bond
INTRODUCTION
Benzophenone is a prototypical aromatic carbonyl compound that has
been extensively studied [1] and are usually obtained from natural
products and by synthetic methods. The great importance of these sub-
stances is fundamentally due to the diverse biological and chemical
properties that they possess [2–11]. Subsequently, benzophenones
are frequently used in medicine and industry [12–17]. The proficiency
of benzophenone analogues as chemotherapeutic agent especially as
anti-inflammatory is well documented [18]. Several scientist have
reported benzophenon analogues as an effective anti-inflammatory
agents [19–22]. Recently, synthesis and structural activity relation-
ship of benzophenones as a novel class of p38 MAP kinase inhibitors
with high anti-inflammatory activity has been reported [23].
Address correspondence to Dr. J. Shashidhara Prasad, Department of Studies in
Physics, Manasagangotri, University of Mysore, Mysore 570 006, India. Fax: þ91-821-
2419333. E-mail: jsp@physics.uni-mysore.ac.in
151

152
S. Neetha et al.
Functionalized phenols, such as 2-hydroxy benzophenones, repre-
sent important building blocks in organic and medicinal chemistry
[24–25]. The in vitro and in vivo studies of novel nitro and
amino-substituted benzophenones have been investigated as potential
anticancer agents with low cytotoxicity [26]. The search for new
molecules with anti-inflammatory activity encouraged us to integrate
p-nitro phenyl moiety in benzophenone framework, which possess
well-documented anti-inflammatory activity.
SYNTHESIS AND METHOD OF CRYSTALLIZATION
4-Chloro-benzoic acid 4-chloro-phenyl ester (3) was synthesized
by benzoylation of 4-chloro-phenol (1) with 4-chloro benzoyl chloride
(2) using 10% sodium hydroxide solution. (5-Chloro-2-hydroxy-
phenyl)-(4-chloro-phenyl)-methanone (4) was synthesized by Fries
rearrangement of the above ester in presence of anhydrous aluminium
chloride. A mixture of 4 (1 g, 4.41 mmol) and 4-nitro benzyl bromide
(0.95 g, 4.41 mmol) was refluxed in dry acetone for 5 h, in the presence
of anhydrous potassium carbonate (1.83 g, 13.25 mmol). The reaction
mass was cooled, and the solvent was removed under reduced pres-
sure. The residual mass was triturated with ice-cold water to remove
FIGURE 1 Schematic diagram.

Synthesis and Crystal Structure
153
TABLE 1 Crystal Data and Structure Refinement Table
CCDC
702891
C20H13Cl2NO4
402.21
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
Space group
293(2) K
˚
0.71073 A
Monoclinic
P21=n
˚
Cell dimensions
a ¼ 9.434(2) A
˚
b ¼ 13.167(3) A
˚
c ¼ 15.087(4) A
b ¼ 105.289(8)ꢀ
3
˚
Volume
1807.7(7) A
Z
4
Density (calculated)
Absorption coefficient
F000
1.478 Mg=m3
0.386 mmꢃ1
824
Crystal size
Theta range for data collection
Index ranges
0.3 ꢂ 0.25 ꢂ 0.25 mm
2.09ꢀ to 25.00ꢀ
ꢃ11 ꢄ h ꢄ 11
ꢃ15 ꢄ k ꢄ 15
ꢃ17 ꢄ l ꢄ 17
Reflections collected
3918
Independent reflections
Absorption correction
Refinement method
Data=restraints=parameters
Goodness-of-fit on F2
Final R indices [I >2r(I)]
R indices (all data)
2672 [R(int) ¼ 0.0450]
None
Full-matrix least-squares on F2
2672=0=245
1.063
R1 ¼ 0.0737, wR2 ¼ 0.1945
R1 ¼ 0.0900, wR2 ¼ 0.2206
0.001(9)
Extinction coefficient
Largest diff. peak and hole
ꢃ3
˚
0.255 and ꢃ0.257 eA
potassium carbonate and then extracted with dichloromethane
(3 ꢂ 20 ml). The organic layer was washed with 10% sodium hydroxide
solution (3 ꢂ 10 ml) followed with water wash (3 ꢂ 15 ml) and then
dried over anhydrous sodium sulfate and evaporated to dryness under
reduced pressure to obtain the crude solid, which recrystallization
with ethanol yielded [5-chloro-2-(4-nitro-benzyloxy)-phenyl]-(4-
chloro-phenyl) methanone (5) as pale yellow crystals, the yield
was good. Figure 1 gives the schematic diagram of the molecule.
C,H,N analysis: Calculated %: C: (73.12), H: (5.30), N: (3.88). Found %:
C: (73.06), H: (5.28), N: (3.80). 1H NMR(CDCl3): d 2.31 (s, 3 H, CH3), 2.41
(s, 3 H, CH3), 4.9 (s, 2 H, CH2), 7.17–7.36 ppm (m, 11 H, Ar-H). IR (Nujol):
1716 cmꢃ1 (C ¼ 0). M.P.: 167ꢀC. Yield: 88% (1.40 g).

154
S. Neetha et al.
TABLE 2 Atomic Coordinates and Equivalent Thermal Parameters
of the Non-Hydrogen Atoms
Atom
x
y
z
Ueq
O1
N2
O3
C4
C5
C6
C7
C8
0.6628(3)
0.5750(3)
0.5187(5)
0.5374(4)
0.4516(4)
0.4219(4)
0.4732(3)
0.5578(4)
0.5903(4)
0.4394(4)
0.3801(3)
0.3398(3)
0.2678(3)
0.2314(3)
0.2635(4)
0.3326(4)
0.3705(4)
0.21317(1)
0.2326(4)
0.2537(4)
0.1665(3)
0.0763(4)
0.0127(4)
0.0439(4)
0.1336(4)
0.1927(4)
ꢃ0.03151(1)
1.0642(2)
1.0337(3)
1.0898(3)
0.9251(3)
0.8897(3)
0.7872(3)
0.7207(3)
0.7601(3)
0.8623(3)
0.6094(3)
0.5828(2)
0.4841(3)
0.4634(3)
0.3636(3)
0.2864(3)
0.3061(3)
0.4048(3)
0.16180(8)
0.5449(3)
0.5290(3)
0.6427(3)
0.6476(3)
0.7385(3)
0.8249(3)
0.8232(3)
0.7313(3)
0.94037(8)
0.2896(2)
0.3287(2)
0.3732(4)
0.3247(2)
0.3795(3)
0.3770(3)
0.3218(2)
0.2677(2)
0.2684(3)
0.3173(2)
0.39123(2)
0.3983(2)
0.4668(2)
0.4818(2)
0.4285(2)
0.3607(3)
0.3463(3)
0.44568(8)
0.5271(3)
0.60891(2)
0.4868(2)
0.3970(3)
0.3611(2)
0.4145(3)
0.5039(3)
0.5391(3)
0.36776(8)
0.0989(8)
0.0903(9)
0.1572(2)
0.0783(9)
0.0883(1)
0.0863(1)
0.0742(8)
0.0820(9)
0.0815(9)
0.0769(8)
0.0847(7)
0.0739(8)
0.0754(8)
0.0784(9)
0.0789(9)
0.0812(9)
0.0810(9)
0.0959(4)
0.0799(9)
0.1060(9)
0.0743(8)
0.0799(9)
0.0827(9)
0.0798(9)
0.0842(9)
0.0841(1)
0.1009(5)
C9
C10
O11
C12
C13
C14
C15
C16
C17
Cl18
C19
O20
C21
C22
C23
C24
C25
C26
Cl27
ꢀ
ꢁ
P P
Ueq ¼ ð1=3Þ
j Uij aꢅi aꢅj ðai ꢁ ajÞ.
i
CRYSTAL STRUCTURE DETERMINATION
single crystal of the title compound with the dimensions
A
0.30 ꢂ 0.25 ꢂ 0.25 mm was chosen for the X-ray diffraction study.
The data were collected on a DIPLabo Image Plate system equipped
with a normal focus, 3 kW sealed X-ray source (graphite monochro-
mated Moka). The crystal to detector distance was fixed at 120 mm
with the detector area of 441 ꢂ 240 mm2. Thirty-six frames of data
were collected at room temperature by the oscillation method. Each
exposure of the image plate was set to 400 s. Successive frames
were scanned in steps of 5ꢀ per minute with an oscillation range
of 5ꢀ. Image processing and data reduction were done using Denzo
[27]. The reflections were merged with Scalepack [28]. All the frames

Synthesis and Crystal Structure
155
˚
TABLE 3 Bond Lengths (A)
Atoms
Length
Atoms
Length
O1-N2
N2-O3
N2-C4
C4-C9
C4-C5
C5-C6
C6-C7
C7-C8
C7-C10
C8-C9
C10-O11
O11-C12
C12-C17
C12-C13
C13-C14
1.207(4)
1.211(5)
1.470(5)
1.371(5)
1.381(5)
1.376(6)
1.381(5)
1.383(5)
1.498(5)
1.380(5)
1.417(4)
1.366(4)
1.382(5)
1.405(4)
1.392(5)
C13-C19
C14-C15
C15-C16
C15-Cl18
C16-C17
C19-O20
C19-C21
C21-C26
C21-C22
C22-C23
C23-C24
C24-C25
C24-Cl27
C25-C26
1.500(5)
1.379(5)
1.375(5)
1.746(4)
1.381(5)
1.215(4)
1.488(5)
1.394(5)
1.399(5)
1.383(5)
1.381(6)
1.391(6)
1.747(4)
1.379(6)
could be indexed using a primitive monoclinic lattice. Absorption cor-
rection was not applied. The structure was solved by direct methods
using SHELXS-97 [29]. Least-squares refinement using SHELXL-97
[29] with isotropic temperature factors for all the non-hydrogen atoms
converged the residual R1 to 0.1595. Subsequent refinements were
carried out with anisotropic thermal parameters for non-hydrogen
atoms and isotropic temperature factors for the hydrogen atoms
which were placed at chemically acceptable positions. The hydrogen
atoms were allowed to ride on their parent atoms. After eight cycles
of refinement the residual converged to 0.0737. The details of crystal
data and refinement are given in Table 1.1 Table 2 gives the atomic
coordinates and equivalent thermal parameters of the non-hydrogen
atoms. Tables 3 and 4 give the list of bond lengths and bond angles
respectively which are in good agreement with the standard values.
The ORTEP of the molecule with thermal ellipsoids drawn at 50%
probability is shown in Fig. 2.
The title compound has independent planar phenyl ring system.
The dihedral angle between the two, 4-chloro-phenyl rings, bridged
˚
by carbonyl group is 64.51(17) A. The atom C23 deviate from the Cremer
˚
and Pople plane [30] C21=C22=C24=C25=C26 by 0.0123(39) A. Torsion
1CCDC 702891 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html
or from The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; Fax: þ44(0)1223–336033. E-mail: deposit@ccdc.cam.ac.uk

156
S. Neetha et al.
TABLE 4 Bond Angles (ꢀ)
Atoms
Angle
Atoms
Angle
O1-N2-O3
O1-N2-C4
O3-N2-C4
C9-C4-C5
C9-C4-N2
C5-C4-N2
C6-C5-C4
C5-C6-C7
C6-C7-C8
121.7(4)
119.6(3)
118.7(4)
122.3(3)
119.3(3)
118.5(3)
117.5(3)
122.4(3)
117.8(3)
122.9(3)
119.3(3)
121.6(3)
118.4(3)
109.3(3)
118.2(3)
124.7(3)
116.1(3)
119.1(3)
119.4(3)
118.2(3)
C12-C13-C19
C15-C14-C13
C16-C15-C14
C16-C15-Cl18
C14-C15-Cl18
C15-C16-C17
C16-C17-C12
O20-C19-C21
O20-C19-C13
C21-C19-C13
C26-C21-C22
C26-C21-C19
C22-C21-C19
C23-C22-C21
C24-C23-C22
C23-C24-C25
C23-C24-Cl27
C25-C24-Cl27
C26-C25-C24
C25-C26-C21
122.4(3)
120.0(3)
121.0(3)
119.3(3)
119.7(3)
119.3(3)
121.3(3)
120.2(3)
119.3(4)
120.4(3)
118.8(3)
120.0(3)
121.3(3)
120.7(3)
118.7(3)
122.4(4)
118.7(3)
119.0(3)
117.9(4)
121.6(3)
C6-C7-C10
C8-C7-C10
C9-C8-C7
C4-C9-C8
O11-C10-C7
C12-O11-C10
O11-C12-C17
O11-C12-C13
C17-C12-C13
C14-C13-C12
C14-C13-C19
angle values of ꢃ136.23(33)ꢀ and 41.16(51)ꢀ for C14-C13-C19-C21 and
C14-C13-C19-C20, respectively, gives ꢃanti-clinal and þsyn-clinal
conformation. The torsion angle about C12=C11=C10=C7 being
˚
179.01(27) A reflects þanti-periplanar conformation w.r.t chlorophe-
nyl and nitroxy phenyl ring, respectively. The keto group in the struc-
ture plays a vital role in the determination of some potent biological
FIGURE 2 ORTEP of the molecule at 50% probability.

Synthesis and Crystal Structure
157
FIGURE 3 Packing of the molecules down the b axis. The dashed lines repre-
sent the hydrogen bonds.
activities [20]. The structure exhibits intermolecular hydrogen bonds
˚
of the type C–H ꢁ ꢁ ꢁ O. C9–H9 ꢁ ꢁ ꢁ O20 has a length of 3.489(5) A with
an angle of 168ꢀ and C10–H10B ꢁ ꢁ ꢁ O20 which has a length of
ꢀ
˚
3.353(5) A and an angle of 158 with symmetry codes 1=2 þ x, 3=2 ꢃ
y, ꢃ1=2 þ z, and 1 ꢃ x, 1 ꢃ y, 1 ꢃ z, respectively. The stability of the
crystal structure can be accounted for by these hydrogen bonds. Pack-
ing of the molecules down b axis is shown in Fig. 3.
ACKNOWLEDGMENTS
The authors would like to express their thanks to DST, Government of
India, for financial assistance under the project SP=I2=FOO=93.
REFERENCES
[1] Du, Y., Ma, C., Kwok, W. M., Xue, J., & Philips, D. L. (2007). J. Org. Chem., 72,
7149.
[2] Moffett, R. B., & Sey, P. P. H. (1964). J. Med. Chem., 7, 178.

158
S. Neetha et al.
[3] Wiesner, J., Kettler, K., Sakowski, J., Ortmann, R., Jomaa, H., & Schlitzer, M.
(2003). Bioorg. Med. Chem., 13, 361.
[4] Winter, Walter, R., Riscoe, Kerin, M., Hinrich, & David, J. (1997). PCT Int.
9707790, Through Chem. Abstr., 126, 248760.
[5] Sanji, H., Susumce, K., Yasushi, M., Nobuhiro, H., Yasunobu, & Toshiro, K. (1995).
PCT Int. 9521856, Through Chem. Abstr., 124, 56716.
[6] Saettone, M. F., Alderigi, C., Giannaccini, B., Anselmi, C., Rosselt, M. G., Schotton,
M., & Gerini, R. (1998). Int. J. Cosmet. Sci., 10, 99.
[7] Bernadi, A. P. M., Ferraz, A. B. F., Albring, D. V., Birdignon, S. A. L., Schripsema,
J., Bridi, R., Dutra-Filho, C. S., Henriques, A. T., & Von Poser, G. L. (2005). J. Nat.
Prod., 68, 784.
[8] Saharia, G. S., & Sharma, H. R. (1979). Sci. Cult., 45, 139.
[9] Pierre, D., Jacques, B., Matthias, K., & Corina, B. (2002). PCT Int. 2002092552,
Through Chem. Abstr., 137, 384655.
[10] Singh, N. A., Indra, D., Setty, B. S., & Ray, S. (1994). Indian J. Pharm. Sci. 56, 105.
[11] Bakana, P., Claeys, M., Totte, J., Pieters, L. A., Van Hoof, L., Vemba, Y., Berghe,
V. D. A., & Vlietinck, A. J. (1987). J. Ethnopharmacol., 21, 75.
[12] Leonard, D. M. (1997). J. Med. Chem., 40, 2971.
[13] Williams, T. M., & Dinsmore, C. (1999). J. Adv. Med. Chem., 4, 273.
[14] Palomer, A., Pascual, J., Cabre, M., Borras, L., Gonzalez, G., Aparici, M., Carabaza,
A., Cabre, F., Garcia, M. L., & Mauleon, D. (2002). Bioorg. Med. Chem. Lett., 12,
533.
[15] Jaques, M., & Walter, S. (1983). Eur. Pat., 79, 499. Through Chem. Abstr., 99,
83726j, (1983).
[16] Hejaz, A. A. M., Woo, L. W. L., Purohit, A., Reed, M. J., & Potter, B. V. L. (2004).
Bioorg. Med. Chem., 12, 2759.
[17] Mitsch, A., Wibner, P., Sibler, K., Haebel, P., Satler, I., Klebe, G., & Schlitzer, M.
(2004). Bioorg. Med. Chem., 12, 4585.
[18] Katsuichi, S., & Massaki, T. (1992). Chem. Abstr., 116, 128368g.
[19] Ottosen, E. R., Sorensen, M. D., Bjorkling, F., Skak-Nielsen, T., Fjording, M. S.,
Aaes, H., & Binderup, L. (2003). J. Med. Chem., 46, 5651.
[20] Khanum, S. A., Shashikanth, S., & Deepak, A. V. (2004). Bioorg. Chem., 32, 211.
[21] Khanum, S. A., Shashikanth, S., & Sudha, B. S. (2004). Heteroatom Chem., 15, 37.
[22] Khanum, S. A., Shashikanth, S., & Sudha, B. S. (2004). Pestmanag. Sci., 60, 1119.
[23] Mahendra, M., Doreswamy, B. H., Sridhar, M. A., Shashidhara Prasad, J.,
Khanum, S. A., Shashikanth, S., & Venu, T. D. (2005). J. Chem. Cry., 35, 463.
[24] Martin, R. (2005). Handbook of Hydroxyacetophenones: Preparation and Physical
Properties, 2nd Ed., Springer: Berlin.
[25] Vane, J. R. (1992). Aspirin and Other Salicylates, Chapman and Hall Medical:
London.
[26] Winter, C. A., Risley, E. A., & Nuss, G. W. (1962). Proc. Soc. Exp. Biol. New York,
111, 544.
[27] Otwinowski, Z., et al. (1997). In: Methods in Enzymology, 276, Carter Jr., C. W., &
Sweet, R. M. (Eds.), Academic Press: New York, 307.
[28] Mackay, S., et al. (1999). maXus Computer Program for the Solution and
Refinement of Crystal Structures, Bruker Nonius: The Netherlands.
[29] Sheldrick, G. M. (1997). SHELXS-97. Program for Crystal Structure Solution,
University of Go¨ttingen: Germany.
[30] Cremer, D., & Pople, J. A. (1975). J. Amer. Chem. Soc., B12, 1354–1358.