ANALYTICAL SCIENCES 2003, VOL. 19 2003 © The Japan Society for Analytical Chemistry
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X-ray Structure Analysis Online
Synthesis and Crystal Structure of (3,4-dimethoxy phenyl)(2-chlorophenyl)methanone Madegowda MAHENDRA,* Beeranahally H. DORESWAMY,* Belagur S. SUDHA,** Shaukath A. KHANUM,** Sheena SHASHIKANTH,** Mandayam A. SRIDHAR,** and Javaregowda. S. PRASAD*† *Department of Studies in Physics, University of Mysore, Manasagangotri, Mysore 570 006, India **Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India
Benzophenone analogue (3) has been synthesized and characterized by X-ray diffraction method. The compound crystallizes in monoclinic space group P21/a with cell parameters a = 10.9500(7)Å, b = 10.9670(7)Å, c = 11.0740(7)Å and Z = 4. The structure exhibits intermolecular hydrogen bonding of the type C–H···O. The dimer structure is observed in the molecular packing diagram. The methoxy and chloro substituents play an important role for their biological activity. (Received July 14, 2003; Accepted August 25, 2003; Published on Web November 11, 2003)
Broad-spectrum sunscreens are being used to protect the skin against aging and in the treatment of photo-dermatoses, where Ultra Violet A (UVA) protection can be vital. Benzophenone derivatives are widely used in sunscreen lotions for UVA Benzophenone derivatives are useful for protection.1 controlling phytopathogenic fungi and fungi diseases; (2,6dichlorophenyl)(2,5-dimethoxy-3-methylphenyl)methanone at 100 ppm controlled 100% barley and wheat Erysiphe graminis.2 Recently, Phenstatin, a benzophenone-type Combretastatin A-4 analogue synthesized by Pettit’s group, has been found to be a very strong cytotoxic agent3 and also to be structurally related to CA-4. It showed excellent cytotoxic activities against a panel of human cancer cell lines including multi-drug resistant cell lines.4 In view of these observations, we have synthesized (3,4dimethoxyphenyl)(2-chlorophenyl)methanone (3) as per the Scheme and investigated it by X-ray diffraction. Polyphosphoric acid (PPA), an efficient catalyst for acylation, was obtained from P2O5 (80 g) and H3PO4 (100 ml) at 160 – 180˚C; varatrole (1) (14.9 ml, 0.117 mol) was added at 80˚C in drops and strirred for 15 min; followed by the addition of 2chlorobenzoic acid (2) (20.3 g, 0.13 mol) at 90 – 100˚C. The mixture was stirred vigorously for 3 h. The reaction mixture poured into ice; the solid was digested with 10% NaOH (100 ml) and washed with water; when recrystallised from ethanol, it gave (3) in 90% yield.
Fig. 1
Scheme.
† To whom correspondence should be addressed. E-mail:
[email protected]
A single crystal of 3 of dimensions 0.15 × 0.2 × 0.15 mm was chosen for X-ray diffraction studies. The experimental crystallographic details are given in Table 1. The structure was solved by direct methods and refined by full-matrix least squares methods with anisotropic temperature factors for the non-H atoms. All H atoms were placed at chemically acceptable positions and were refined with isotropic temperature factors. The final cycle of full-matrix least squares refinement based on 4602 obseved reflections and 172 parameters, converged the residual R to 0.0553 with wR = 0.1486. The final coordinates and equivalent thermal parameters of non-H atoms are listed in Table 2. Table 3 gives selected bond distances and bond angles which agree with their
Table 1
Crystal and experimental data
Formula: Formula weight Crystal system Space group a b c β V Dx 2θ max No. of reflecftions used (I > 2σ (I)) R (∆/σ )max (∆ρ )max (∆ρ )min Measurement Program system Structure determination Refinement
C15H13O3Cl 276.70 monoclinic P21/a, Z = 4 10.9500(7)Å 10.9670(7)Å 11.0740(7)Å 97.036(2)˚ 1319.85(15)Å3 1.393 Mg/m3 64.94˚ with Mo Kα 3348 0.0553 0.000 0.376 eÅ3 –0.517 eÅ3 DipLabo Kappa Denzo SHELXS-97 fullmatrix: SHELXL-97
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ANALYTICAL SCIENCES 2003, VOL. 19
Table 2 Atomic coordinates and equivalent temperature factors (Å2) Atom
x
y
z
Ueq
Fig. 2
Ueq = (1/3)ΣiΣjUij(ai*aj*)(ai·aj).
Table 3
Selected bond lengths (Å) and bond angles (˚)
ORTEP of the molecule at 50% probability.
structure around the center of symmetry. The molecular packing shows that each dimer structure unit are stacked independently (when viewed down b axis). The crystal structure shows that the substitution of chloro group at the ortho position and two methoxy groups at meta and para positions in benzophenone nucleus are important for their fungicidal activity,2 and such chloro and methoxy substituent compounds are used in the synthesis of phenstatin as an antitumour agent.5
Acknowledgements The authors would like to express their thanks to DST, Government of India for financial assistance under the project SP/I2/FOO/93.
References
standard values. Figure 2 represents the ORTEP diagram of the molecule with thermal ellipsoids at 50% probability. Both the phenyl rings are independently planar without much deviation. The two planar rings are bridged via a carbonyl group; the dihedral angle between them is 75.2˚. The structure exhibits intermolecular hydrogen bonding of the type C–H···O and helps in stabilizing the crystal structure due to their weaker van der Waals forces. The intermolecular distance between atoms is as follows: C10–H10···O17 has length 3.439(2)Å and an angle of 147˚, with symmetry code (1 – x, –y, 2 – z) respectively. This intermolecular hydrogen bond forms a dimer
1. H. Deleu, A. Maes, and R. Roelandts, Photodermatol. Photoimmunol. Photomed., 1992, 9, 29. 2. J. Curtz, C. Pudolph, G. Helene, L. Schroeder, G. Albert, A. Rehnig, E. Edith, Sieverding and G. Ewals, Can. Pat Appl., 1996, CA 2167550 AA, 100. 3. G. R. Pettit, B. Toki, D. L. Herald, P. Verdier-Pinard, M. R. Boyd, E. Hamel, and R. K. Pettit, J. Med. Chem., 1998, 41, 1668. 4. H. Hsing-Pang, L. Jing-Ping, L. Ying-Ting, N. Mahindroo, C. Jang-Yang, Y. Yung-Ning, C. Shuenn-Shing, T. UanKang, C. Chun-Wei, C. Tung-Wei, L. Chi-Hung, C. YingYang and Chiung-Chiu, Bio. Med. Chem. Let., 2003, 13, 101. 5. G. R. Pettit and T. Brian, PCT. Int. Appl. Wo., 1999, 9934788 A1, 39.
