Crystal structure studies of two regioisomers of bromo-4- aryloxymethylcoumarins

Article abstract of DOI:10.1007/s10870-010-9917-1

The 4-(2-bromo-4-methyl-phenoxymethyl)-6- methylcoumarin (1) have been synthesized from bromination of corresponding 4-aryloxymethyl coumarin, which is a regioisomer of 4-(2-bromo-4-methyl-phenoxymethyl)- 7-methylcoumarin (2) (CCDC-695895). The compound 1

Full text of DOI:10.1007/s10870-010-9917-1

J Chem Crystallogr (2011) 41:541–544
DOI 10.1007/s10870-010-9917-1
ORIGINAL PAPER
Crystal Structure Studies of Two Regioisomers
of Bromo-4-Aryloxymethylcoumarins
•
Manantesha Basanagouda Manohar V. Kulkarni
•
•
Deepak Sharma Vivek K. Gupta
Received: 19 July 2009 / Accepted: 28 November 2010 / Published online: 15 December 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The 4-(2-bromo-4-methyl-phenoxymethyl)-6-
methylcoumarin (1) have been synthesized from bromina-
tion of corresponding 4-aryloxymethyl coumarin, which is
a regioisomer of 4-(2-bromo-4-methyl-phenoxymethyl)-
7-methylcoumarin (2) (CCDC-695895). The compound 1
crystallizes with triclinic space group P-1, a = 8.0943(3)
hydrogen bonding, eclipsed conformation observed in
3-bromocoumarin [9], 6-bromo-3-acetylcoumarin [10] and
3-bromoacetylcoumarin [11], respectively. 3-Bromophenyl-
6-acetoxymethyl-coumarin-3-carboxylates have been found to
exhibit potential anticancer and antitumour activity [12].
The present paper reports the synthesis and crystal
structures of two regioisomers of 4-aryloxymethylcouma-
rins possessing bromine in the aryloxy moiety obtained by
the room temperature bromination of 4-p-tolyloxymethyl
coumarins (Scheme 1) [13, 14].
˚
˚
˚
A, b = 9.3502(3) A, c = 10.1476(4) A, a = 90.234(2)°,
b = 94.065(2)°, c = 95.106(2)°, Z = 2 and compound
2 crystallizes with monoclinic space group P21/n, a =
˚
˚
˚
8.465(5) A, b = 13.649(5) A, c = 13.304(5) A, a = 90.
000(5)°, b = 90.740(5)°, c = 90.000(5)°, Z = 4. Both the
compounds are planar with variation in their intermolecular
hydrogen bonds between C–HÁÁÁO and C–HÁÁÁp.
Experimental
Keywords Coumarin Á Electrophilic substitution Á
Spectroscopic studies Á Crystal structure
All the starting materials and reagents were purchased from
Aldrich (USA) and used after further purification [15]. Thin
layer chromatography was performed with TLC sheets
coated with silica (Merck, Germany). The purity of the
compound was checked by TLC. Melting points were
determined by open capillary method and are uncorrected.
Carbon, hydrogen and nitrogen analyses were performed on
Heraus CHN rapid analyzer. Infrared absorption spectra
(KBr disc) were obtained from a Nicolet-5700 FT-IR spec-
trophotometer. The 1H and 13C NMR spectra were recorded
on a Bruker 400 MHz spectrometer using CDCl3 as a solvent
and tetramethylsilane (TMS) as an internal standard. The
chemical shifts are expressed in d ppm scale down field from
TMS and proton signals are indicated as s = singlet,
d = doublet, t = triplet and m = multiplet. The mass
spectra were recorded using Agilent-single Quartz LC-MS.
Introduction
Coumarins are a class of naturally occurring oxygen het-
erocycles which have been found to exhibit wide ranging
biological activities [1–3] through its innumerable deriva-
tives. Structural studies on coumarins have been focused on
their solid state photochemical dimerization [4], hydrogen
bonding [5], mode of packing [6], molecular self assembling
[7] and photophysical properties [8]. Introduction of bro-
mine has resulted in formation of hydrates, intermolecular
M. Basanagouda Á M. V. Kulkarni (&)
Post-Graduate Department of Chemistry,
Karnatak University, Dharwad, Karnataka 580 003, India
e-mail: manohar274@gmail.com
Synthesis
D. Sharma Á V. K. Gupta
Synthesis of 4-(2-Bromo-4-Methyl-Phenoxymethyl)-6-Meth-
ylcoumarin 1: The compound a (2.80 g, 10 mmol) was
Post-Graduate Department of Physics, University of Jammu,
Jammu Tawi 180 006, India
123

542
J Chem Crystallogr (2011) 41:541–544
Scheme 1 Synthesis of the
compound 1
CH3
CH3
Br
O
O
H3C
H3C
Br2 / CHCl3
O
O
O
O
(a)
(1)
dissolved in 25 mL of chloroform, and to this bromine
(0.52 mL, 10 mmol) in 25 mL of chloroform was added with
stirring, and stirring was continued for 6 h (reaction was
monitored by TLC), the solid separated 1 was filtered, dried,
and recrystallised from ethylacetate by slow evaporation
technique. Colourless solid (white transparent plate), mp.
228 °C, yield 80%; IR (KBr, t in cm-1): 1716 (lactone C=O),
1559 (C=C), 1146 (C–O–C), 2922 (=CH); 1H NMR
(400 MHz, CDCl3): d 2.31 (s, 3H, C18–CH3), 2.44 (s, 3H,
C9–CH3), 5.26(s, 2H, C10–CH2), 6.80(s, 1H, C3–H), 6.87(d,
1H, J = 8.25 Hz, Ar–H), 7.07 (d, 1H, J = 8.04 Hz, Ar–H),
7.31 (s, 1H, Ar–H), 7.38–7.43 (m, 2H, Ar–H), 7.44 (s, 1H,
C5–H); 13C NMR (CDCl3, 100 MHz): 20.22, 21.67, 66.62,
112.27, 112.68, 113.61, 114.67, 117.57, 123.05, 125.54,
128.93, 133.06, 134.18, 143.27, 149.46, 151.98, 153.76,
160.83; LCMS m/z: 361 [M?2]; Anal.calc. for C18H15BrO3;
C, 60.18; H, 4.21; Found: C, 60.25; H, 4.23.
Table 1 Crystal and experimental data
Compound
1
CCDC deposition no.
Empirical formula
Temperature (K)
Formula weight
Color/shape
704679
C18H15BrO3
293 (2)
359.21
White transparent/plate
0.3 9 0.2 9 0.2 mm
0.71073
Crystal size
Wavelength
Crystal system
Space group
Triclinic
P-1
˚
a = 8.0943(3) A
Unit cell parameters
˚
b = 9.3502(3) A
˚
c = 10.1476(4) A
a = 90.234(2)°
b = 94.065(2)°
c = 95.106(2)°
Synthesis of 4-(2-Bromo-4-Methyl-Phenoxymethyl)-
7-Methylcoumarin 2: [14].
3
˚
Volume, V
732.99(5) A
Z
2
Density (calculated)
Absorption coefficient
F (000)
1.564 Mg m-3
2.704 mm-1
364
h range for data collection
Absorption correction
2.53°–30.42°
Multi-scan (Tmin = 0.4976,
Tmax = 0.6139)
Limiting indices
-11 B h B 11, -13 B k B 13,
-14 B l B 14
Reflections collected/unique
Data/restraints/parameters
Goodness-of-fit
19465/4546 [R(int) = 0.0339]
4546/0/259
1.032
Final R indices [I [ 2sigma(I)] R1 = 0.0384, wR2 = 0.0896
-3
˚
0.602 and -0.278 e A
Largest diff. peak and hole
Measurement
Bruker SMART CCD area-detector
diffractometer
Program system
Structure determination
Refinement
SHELX-97
Direct methods
Full matrix least squares on F2
ORTEP
Structure drawing
Fig. 1 ORTEP drawing of the compound 1 with atom labeling
123

J Chem Crystallogr (2011) 41:541–544
543
SHELXS-97 and refined with SHELXL-97 [17, 18]. The
positions of the H atoms were located in difference maps
and then refined.
Table 2 Geometry of p–p interactions
˚
˚
˚
CgI CgJ CgIÁÁÁCgJ (A) CgIÁÁÁP (A) a (°) b (°)
D (A)
Compound 1
3i
1
3.534 (1)
3.385
3.70
16.98 1.01
Compound 2
Results and Discussion
1
3
3ii
3iii
3.619 (2)
3.608 (2)
3.486
3.547
3.55
0.02
15.60 0.97
10.56 0.66
Two regioisomers 4-(2-bromo-4-methyl-phenoxymethyl)-6-meth-
ylcoumarin (1) and 4-(2-bromo-4-methyl-phenoxymethyl)-
7-methylcoumarin (2) [14] have been synthesized from
bromination of corresponding 4-aryloxymethyl coumarins
[19] as shown in Scheme 1. In order to confirm the struc-
tures, the products were subjected to the spectroscopic
analysis using IR, 1H-NMR, 13C-NMR, Mass and elemental
analysis. The spectral data of the compound is given in the
synthetic procedure.
Symmetry code: (i) 1 - x, 2 - y, -z, (ii) 1 - x, -y, 1 - z (iii) -x,
-y, 1 – z
Cg represents the center of gravity of the following rings: Cg1 ring A
and Cg3 ring C. CgIÁÁÁCgJ represents the distance between the ring
centroids; CgIÁÁÁP, the perpendicular distance of the centroid of one
ring from the plane of the other; a is the dihedral angle between the
planes of rings I and J; b is the angle between normal to the centroid
of ring I and the line joining ring centroids; D is the displacement of
the centroid of ring J relative to the intersection point of the normal to
the centroid of ring I and the least-squares plane of ring J
Crystals of suitable quality for single crystal X-ray dif-
fraction were obtained by slow evaporation technique from
ethylacetate. The details of the X-ray data collection,
structure solution and structure refinements are given in
Table 1. The molecular structure with the atom-numbering
scheme is shown in Fig. 1.
X-Ray Structure Determination
The data collection for both compounds was performed on
a Bruker SMART CCD Area Detector employing graphite-
In both the compounds 1 and 2, the bond angles,
C5–C4a–C4 and C8–C8a–O1, at the junction of the pyrone
and benzene rings are, respectively, greater and smaller
than 120°. This phenomenon has also been observed in
some analogous coumarins. The widening of the angle,
˚
monochromatized Mo Ka radiation (k = 0.71073 A). Data
collection, reduction and corrections for absorption for
compound 1 and 2 were achieved using SMART, SAINT
and SADABS software [16]. The structures were solved by
Fig. 2 Crystal perspective view
diagram of the compounds 1
and 2
123

544
J Chem Crystallogr (2011) 41:541–544
Acknowledgments Authors thank the University sophisticated
instrumentation centre (USIC), Karnatak University, Dharwad for
the spectral data. One of the authors, Mr. Mahantesha. Basanagouda
is grateful to Karnatak University, Dharwad for a University
Research Studentship. (D. S and V. K. G) grateful to the Head,
SAIF, IIT Madras, Chennai for providing the intensity data collec-
tion facility.
O2–C2–C3 in 1 and 2, is attributed to lone-pair interactions
between O1 and O2. X-ray structure of the compounds 1
and 2 reveals that both the molecules are planar. The
phenyl ring C and the coumarin moiety are in the same
plane [dihedral angle 3.79(6)° (compound 1) and dihedral
angle 3.80(4)° (compound 2)]. The C4–C10–O11–C12
torsion angle of 179.6(1)° in compound 1 and 177.7(2)° in
compound 2 indicates an anti-periplanar arrangement
across the bridging atoms. In compound 1, hydrogen H17
on atom C17 forms an intermolecular hydrogen bond with
the carbonyl O2 atom of a neighboring molecule at
(1 ? x,1 - y, -z). One C–HÁÁÁp hydrogen bond is also
present which connects the parent molecule to its centro-
symmetrically related molecule at (1 - x, 1 - y, -z).
Molecules are packed together to form infinite two-
dimensional layers parallel to the (001) plane. Molecules
within the layers are arranged in anti-parallel manner and
are stabilized by C–HÁÁÁp and p–pinteractions for com-
pound 1. In both the compounds 1 and 2, the packing
diagram of the molecules indicates p–p contacts (Table 2)
between the phenoxy moiety and the fused pyrone ring of
coumarin moiety. In compound 2, this interaction generates
linkages between symmetry related molecules which have
their molecular planes perpendicular to each other. There is
only one intramolecular hydrogen bond C3–H3ÁÁÁO11 and
References
1. Kulkarni MV, Kulkarni GM, Lin CH, Sun CM (2006) Curr Med
Chem 13:2795
2. Fylaktakidou KC, Hadjpavlou D, Litinas KE, Nicolaides DN
(2004) Curr Pharm Design 10:3813
3. Neyts J, Clercq ED, Singha R, Chang YH, Das AR, Chakraborty
SK, Hong SC, Tsay SC, Hsu MH, Hwu JR (2009) J Med Chem
52:1486
4. Gnanaguru K, Ramasubbu N, Venkatesan K, Ramamurthy V
(1985) J Org Chem 50:2337
5. Munshi P, Row TNG (2005) J Phys Chem A 109:659
6. Gavuzzo E, Mazza F (1974) Acta Cryst B30:1351
7. Murthy JN, Venkatakrishnan P, Singh AS (2003) Cryst Eng
Commun 5:507
8. Katerinopoulos HE (2004) Curr Pharm Des 10:3835
9. Gaultier J, Hauw C (1965) Acta Cryst C19:927
10. Kokila MK, Puttaraja KulkarniMV, Shivaprakash NC (1996)
Acta Cryst C52:2078
11. Puttaraja, Vasudevan KT, Kulkarni MV (1991) Acta Cryst
C47:774
12. Kempen I, Papapostolou D, Thierry N, Pochet L, Counerotte S,
Masereel B, Foidart J-M, Reboud-Ravaux M, Noel A, Pirotte B
(2003) Br J Can 88:1111
˚
the distance between H3ÁÁÁO11 is 2.30 A in compound 1
˚
and 2.42 A in compound 2 (Fig. 2).
13. Puttaraja, Vasudevan KT, Kulkarni MV (1990) Acta Cryst
C46:2129
14. Basanagouda M, Kulkarni MV, Sharma D, Gupta VK, Pranesha,
Sandhyarani P, Rasal VP (2009) J Chem Sci 121:485
15. Furniss BS, Hannaford AJ, Smith PWG, Tatchell AR (1997)
Vogel’s textbook of practical organic chemistry, 5th edn. Addi-
son Wesley Longman, Harlow, England
16. Bruker, SMART (Version 5.0), SAINT (Version 6.02) Aabd
SADABS (Version 2.10). Bruker AXS Inc., Madison, WI
17. Sheldrick GM, SHELXS-97 (1997) Program for the solution of
crystal structures. University of Goettingen, Germany
18. Sheldrick GM, SHELXL-97 (1997) Program for the refinement of
crystal structures. University of Goettingen, Germany
19. Kulkarni MV, Pujar BG, Patil VD (1981) Arch Pharm 316:15
Supplementary Material
CCDC nos. 704679 and 695895 contain the supplementary
crystallographic data for the compounds 1 and 2 [14],
respectively. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif by e-mailing
data_request@ccdc.cam. ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, UK. Fax: ?44(0)1223-336033.
123