Synthesis and structural characterization of 2-benzylidenebenzofuran-3-(2 H)-ones

Article abstract of DOI:10.1080/15421406.2013.782179

Novel aurone derivatives e.g. 2-(2-(3-methylbut-2-enyloxy)benzylidene) benzofuran-3(2H)-one (3a), 2-(2-(allyloxy)benzylidene)-7-methoxybenzofuran-3(2H) -one (3b), and 2-(5-bromo-2-(3-methylbut-2-enyloxy)benzylidene)-6- hydroxybenzofuran-3(2H)-one (3c) were synthesized. All these compounds were characterized by IR, ¹H and ¹³C NMR, and Mass spectroscopy. Finally, the crystal structures were solved by single crystal X-ray diffraction data and the structures were analyzed in terms of supramolecular interactions. [Supplementary materials are available for this article. Go to the publisher's online edition of Molecular Crystals and Liquid Crystals for the following free supplemental resource(s): supplemental figures 1-12; Spectral data (IR, NMR, MS, and HRMS) of the compounds 3a, 3b and 3c are available in the supporting information in.pdf format. Crystallographic information files (.cif) of compounds 3a, 3b, and 3c are available in the electronic format.]

Full text of DOI:10.1080/15421406.2013.782179

This article was downloaded by: [Pennsylvania State University]
On: 05 August 2013, At: 01:49
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 Structural
Characterization of 2-
Benzylidenebenzofuran-3-(2H)-Ones
D. Rambabu a , S. Srinivas b , Khanapur Manjulatha a , Srinivas
Basavoju c , M. V. Basaveswara Rao d & Manojit Pal a
a Institute of Life Sciences , University of Hyderabad Campus ,
Hyderabad , India
b Department of Chemistry , Acharya Nagarjuna University , Guntur ,
India
c Department of Chemistry , National Institute of Technology
Warangal , Warangal , India
d Department of Chemistry , Krishna University , Machilipatnam ,
India
To cite this article: D. Rambabu , S. Srinivas , Khanapur Manjulatha , Srinivas Basavoju ,
M. V. Basaveswara Rao & Manojit Pal (2013) Synthesis and Structural Characterization of 2-
Benzylidenebenzofuran-3-(2H)-Ones, Molecular Crystals and Liquid Crystals, 577:1, 83-94, DOI:
10.1080/15421406.2013.782179
To link to this article: http://dx.doi.org/10.1080/15421406.2013.782179
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. 577: pp. 83–94, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 1542-1406 print/1563-5287 online
DOI: 10.1080/15421406.2013.782179
Synthesis and Structural Characterization
of 2-Benzylidenebenzofuran-3-(2H)-Ones
D. RAMBABU,1 S. SRINIVAS,2 KHANAPUR MANJULATHA,1
SRINIVAS BASAVOJU,3 M. V. BASAVESWARA RAO,4
AND MANOJIT PAL1,∗
1Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, India
2Department of Chemistry, Acharya Nagarjuna University, Guntur, India
3Department of Chemistry, National Institute of Technology Warangal,
Warangal, India
4Department of Chemistry, Krishna University, Machilipatnam, India
Novel aurone derivatives e.g. 2-(2-(3-methylbut-2-enyloxy)benzylidene)benzofuran-
3(2H)-one (3a), 2-(2-(allyloxy)benzylidene)-7-methoxybenzofuran-3(2H)-one (3b),
and 2-(5-bromo-2-(3-methylbut-2-enyloxy)benzylidene)-6-hydroxybenzofuran-3(2H)-
one (3c) were synthesized. All these compounds were characterized by IR, 1H and 13
C
NMR, and Mass spectroscopy. Finally, the crystal structures were solved by single crys-
tal X-ray diffraction data and the structures were analyzed in terms of supramolecular
interactions.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Molecular Crystals and Liquid Crystals for the following free supplemental
resource(s): supplemental figures 1–12; Spectral data (IR, NMR, MS, and HRMS) of the
compounds 3a, 3b and 3c are available in the supporting information in .pdf format.
Crystallographic information files (.cif) of compounds 3a, 3b, and 3c are available in
the electronic format.]
Keywords Aurones; conformational isomers; hydrogen bonding; hydroxybenzofuran-
3(2H)-one; single crystal X-ray diffraction; spectroscopic characterization; supramolec-
ular synthons
Introduction
Naturally occurring aurones (or 2-benzylidenebenzofuran-3(2H)-ones) that belong to a
type of flavonoid class possess a chalcone-like moiety part of which is closed into a 5-
membered ring through an oxygen atom, and an intact exocyclic double bond with restricted
rotations. These are biosynthesized from chalcones in the presence of a key enzyme called
aureusidin synthase or obtained through the biosynthesis of other flavonoids [1]. These
compounds exhibit a wide variety of biological activities, e.g., anticancer, antifeedant,
antiparasitic, antimalarial, antihistamine, and antifungal activities [2–7]. They are also
known as inhibitors of tyrosinase, iodothyronine-deiodinase, acetylcholinesterase, and as
∗Address correspondence to Dr. Manojit Pal, Institute of Life Sciences, University of Hyder-
abad Campus Hyderabad-500 046, India. Tel.: +91-40-66571633; Fax: +91-40-66571581; E-mail:
manojitpal@rediffmail.com
83

84
D. Rambabu et al.
antioxidants [8–11]. There have been reports that some of these substances were synthesized
as fluorescent probes [12–14]. The interesting biological activities and structural feature of
the aurones have stimulated many studies on their synthesis.
These compounds are usually prepared by three main methods, e.g., condensation
between benzofuranones and benzaldehydes, oxidative cyclization of 2-hydroxy chalcones,
or catalyzed cyclization of o-(1-hydroxyprop-2-ynyl)phenols [15–17]. In addition, some
other unusual methods have been reported, such as the Wheeler aurone synthesis from
chalconedihalides and a gold(I) iodide-catalyzed cyclization [18,19]. Furthermore, aurones
have been obtained as byproducts in the Algar–Flynn–Oyamada synthesis of flavonols [20].
The only aurone isolated from the marine source, Spatoglossum variabile (brownalga), was
1
assigned the structure of 4-chloroaurone based on the interpretation of H and 13C NMR
spectral data. The stereochemistry was assigned as Z, based on the calculation of heat
of formations of both Z and E isomers by AM1 (the Austin model 1) method [21–23].
Stereochemistry plays a major role in the drug discovery and development; the biological
activities of aurones were not studied in detail with respect to their double bond geometry
(E/Z). Venkateswarlu et al. reported, Z-stereochemistry is important for the antibacterial
activity [17a]. In this paper, we describe a fast and simple one-pot synthesis of new
aryl-substituted aurones under room temperature conditions. We also present here the
structural characterization of three 2-benzylidenebenzofuran-3-(2H)-one derivatives. All
1
the compounds (3a–c) prepared were well characterized by spectral (IR, H NMR, 13C
NMR, MS and HRMS) data. Thus the structures of compounds 3a–c were examined by
single crystal X-ray diffraction study which confirmed the presence of an exocyclic C C
double bond with Z-geometry.
Experimental
General Procedures and Materials
All reactions were carried out under nitrogen atmosphere. Melting points were determined
on a Bu¨chi B-540 melting point apparatus and were uncorrected. All compounds were
routinely checked by TLC and 1H NMR. TLC was performed on aluminum-backed silica
gel plates (Merck DC, Alufolien Kieselgel 60 F254) with spots visualized by UV light. All
chemicals and reagents (purity >99.8%) were purchased from Aldrich Co. Ltd., Bangalore,
India.
1H and 13C NMR Spectroscopy
1H and 13C NMR spectra were determined in CDCl3 and DMSO solutions using 400 and
100 MHz spectrometers, respectively. Proton chemical shifts (δ) are relative to tetram-
ethylsilane (TMS, δ = 0.0) as internal standard and expressed in parts per million. Spin
multiplicities are given as s (singlet), d (doublet), t (triplet), and m (multiplet) as well as b
(broad). Coupling constants (J) are given in Hertz.
Infrared Spectroscopy
Jasco FT–IR 4200 (Easton, Maryland) type-A Fourier transform infrared spectrophotometer
was used to record the IR spectra of the samples (sample concentration is 2 mg in 20 mg
of KBr). The spectra were recorded over the range of 4000–600 cm−1. Data were analyzed
using spectrum version 2 software (JASCO, Easton, Maryland, USA).

2-Benzylidenebenzofuran-3-(2H)-Ones
High Resolution Mass Spectra (HRMS)
85
High resolution mass spectra (HRMS) were measured on a Waters LCT Premier XE
instrument (Waters Model: LCT Premier XE, Bath, United Kingdom).
Synthesis
The key starting materials, i.e., benzofuran-3(2H)-one (1a), 7-methoxybenzofuran- 3(2H)-
one (1b), and 6-hydroxybenzofuran-3(2H)-one (1c) required for our synthesis were pre-
pared from the corresponding phenols (Scheme 1). Thus, phenol, 2-methoxy phenol and
hydroxy phenol were O-alkylated with chloroacetic acid in the presence of sodium hydride
to yield the desired phenoxyacetic acid intermediates, respectively, which on intramolecular
Friedel-Crafts type cyclization [24a] provided the desired compounds 1a–c. Benzaldehydes
2a–c were prepared via alkylation, e.g., allylation and prenylation of salicylaldehyde and
5-bromo salicylaldehyde, using allyl bromide and prenyl bromide (1-bromo-3-methyl-2-
butene) [24b,c].
Scheme 1. Reagents and Conditions: (a) chloroacetic acid (1.1 eq), NaH, DMF, room temp, 12 h;
(b) polyphosphoric acid, 80◦C, 8 h.
2-(2-(3-methylbut-2-enyloxy)benzylidene)benzofuran-3(2H)-one, (3a)
To a solution of benzofuran-3(2H)-one, 1a (0.07 g, 0.5 mmol) in acetonitrile (5 mL) was
added ethylenediamine diacetate (EDDA) (0.0094 g, 10% mol) followed by O-prenylated
salicylaldehyde, 2a (0.1 g, 0.5 mmol). The reaction mixture was stirred for 1.5 h at room
temperature. The precipitate was collected by filtration and crystallized from ethanol to
1
afford the pure compound 3a as yellow solid (yield: 85%); mp: 89◦C–91◦C; H NMR
(400 MHz, CDCl3): δ 8.32 (d, J = 7.7 Hz, 1H), 7.82 (d, J = 7.6 Hz, 1H), 7.64 (t, J =
7.7 Hz, 1H), 7.51 (s, 1H), 7.34 (dd, J = 15.6, 7.2 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.06 (t,
J = 7.6 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 5.53 (t, J = 6.3 Hz, 1H), 4.62 (d, J = 6.5 Hz,
2H), 1.81 (s, 3H), 1.76 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 184.7, 158.3, 155.6, 146.8,
145.9, 137.9, 132.2, 131.4, 123.6, 123.3, 121.6, 120.8, 119.5, 118.4, 115.8, 108.1, 65.5,
29.6, 25.7, 18.2; IR (KBr)vmax 3032, 1698, 1647, 1297, 1242, 996, 887 cm−1; MS (ES
mass): m/z 307 (M+1, 100%); HRMS: calcd, for C20H19O3: 307.1324, found 307.1328.
2-(2-(allyloxy)benzylidene)-7-methoxybenzofuran-3(2H)-one, (3b)
To a solution of 7-methoxy benzofuran-3(2H)-one, 2a (0.101 g, 0.61 mmol) in acetonitrile
(5 mL) was added ethylenediamine diacetate (EDDA) (0.011 g, 10% mol) followed by
O-allylated salicylaldehyde, 2b (0.1 g, 0.61 mmol). The reaction mixture was stirred for
1.3 h at room temperature. The precipitate was collected by filtration and crystallized from
ethanol to afford the pure compound, 3b as yellow solid (yield: 92.8%); mp: 145◦C–147◦C;

86
D. Rambabu et al.
1H NMR (400 MHz, CDCl3): δ 8.36 (d, J = 8.1 Hz, 1H), 7.54 (s, 1H), 7.40–7.32 (m, 2H),
7.17–7.06 (m, 3H), 6.92 (d, J = 8.4 Hz, 1H), 6.15–6.05 (m, 1H), 5.44 (d, J = 17.2 Hz,
1H), 5.32 (d, J = 10.49 Hz, 1H), 4.65 (d, J = 5.13 Hz, 2H), 4.03 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 184.7, 157.8, 155.6, 146.9, 145.9, 132.8, 132.2, 131.3, 123.7, 123.2,
121.5, 121.1, 118.5, 117.8, 115.8, 112.0, 107.7, 69.3, 56.3; IR (KBr)vmax 3055, 1697, 1649,
1277, 1239, 950, 906 cm−1; MS (ES mass): m/z 308.9 (M+1, 100%); HRMS: calcd, for
C19H17O4: 309.1127, found 309.1118.
2-(5-bromo-2-(3-methylbut-2-enyloxy)benzylidene)-6-hydroxybenzofuran-
3(2H)-one, (3c)
To a solution of 6-hydroxy benzofuran-3(2H)-one, 1c (0.05 g, 0.36 mmol) in acetonitrile
(5 mL) was added ethylenediamine diacetate (EDDA) (0.0097 g, 10% mol) followed
by 5-bromo-O-prenylated salicylaldehyde, 2c (0.1 g, 0.36 mmol). The reaction mixture
was stirred for 1.5 h at room temperature. The precipitate was collected by filtration and
crystallized from ethanol to afford the pure compound, 3c as yellow solid (yield: 89.5%);
1
mp: 260◦C–261◦C; H NMR (400 MHz, CDCl3 + DMSO-d6): δ 8.33 (d, J = 2.1 Hz,
1H), 7.63 (d, J = 8.4 Hz, 1H), 7.44–7.36 (m, 2H), 7.21 (s, 1H), 6.80 (d, J = 9.2 Hz,
1H), 6.76 (s, 1H), 6.71–6.69 (m, 1H), 5.54–5.46 (m, 1H), 4.58 (d, J = 6.54 Hz, 2H),
1.80 (s, 3H), 1.74 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 181.5, 167.9, 166.6, 156.3,
147.8, 138.0, 133.1, 132.9, 125.7, 123.0, 118.9, 114.2, 113.0, 112.7, 112.6, 102.6, 98.6,
65.5, 25.5, 18.0; IR (KBr)vmax 3200, 2980, 1670, 1635, 1574, 1296, 1242, 986, 897 cm−1
;
MS (ES mass): m/z 401 (M+1, 100%); HRMS: calcd, for C20H18BrO4: 401.0388, found
401.0392.
Crystallization
The three compounds 3a–c each 25 mg were dissolved in the ethanol in three different
conical flasks and heated to aid complete dissolution. The solutions were allowed to slow
evaporation and needle-shaped crystals were obtained in 1–2 days.
Preliminary Characterization
The shapes of crystals of the compounds 3a–c were observed under the LEICA DFC295
polarizing microscope.
Single Crystal X-ray Diffraction
The single-crystal X-ray diffraction data of the crystals (3a–c) were collected on a Bruker
Kappa APEX-II CCD DUO diffractometer at 296(2) K using graphite-monochromated
Mo Kα radiation (λ = 0.71073 Å). No absorption correction was applied. The lattice
parameters were determined from least-squares analysis, and reflection data were inte-
grated using the program SHELXTL [25]. The crystal structures were solved by direct
methods using SHELXS-97 and refined by full-matrix least-squares refinement on F2 with
anisotropic displacement parameters for non-H atoms using SHELXL-97 [26]. The O−H
hydrogens were located from difference Fourier maps. Aromatic and aliphatic C−H hy-
drogens were generated by the riding model in idealized geometries. The software used
to prepare material for publication was Mercury 2.3 (Build RC4), ORTEP-3 and X-Seed

2-Benzylidenebenzofuran-3-(2H)-Ones
87
Table 1. Salient crystallographic data and structure refinement parameters of compounds
3a, 3b and 3c
3a
3b
3c
Empirical formula
Formula weight
C20H18O3
282.32
C19H16O4
308.32
C20H17BrO4
401.24
Crystal system
Space group
T/K
Triclinic
P-1
296(2)
Orthorhombic
Pbcn
Orthorhombic
P212121
296(2)
296(2)
a/Å
b/Å
8.4961(5)
8.8991(5)
11.0041(7)
77.447(3)
83.382(3)
81.717(3)
2
800.59(8)
1.171
300
27.9594(10)
7.3164(3)
15.2280(6)
90.00
90.00
90.00
8
3115.1(2)
1.315
1296
13.2187(15)
13.3753(15)
20.304(2)
90.00
90.00
90.00
8
3589.9(7)
1.485
1632.0
c/Å
α/◦
β/◦
γ /◦
Z
V/Å3
Dcalc/g/cm3
F(000)
μ/mm−1
θ/◦
0.079
0.092
3.433
1.90 to 27.00
−10 ≤ h ≤ 10
−11 ≤k ≤ 11
−14 ≤ l ≤ 14
17668
1.46 to 27.00
−34 ≤ h ≤ 34
−9 ≤ k ≤ 9
−19 ≤ l ≤ 19
35537
2.39 to 18.82
−10 ≤ h ≤ 12
−12 ≤ k ≤ 10
−18 ≤ l ≤ 18
14081
Index ranges
N-total
N-independent
N-observed
Parameters
R1 (I > 2σ(I))
wR2 (all data)
GOF
3485
2805
210
0.0555
0.1616
1.301
3392
2660
209
0.0402
0.1326
1.117
2973
2392
457
0.0289
0.0771
0.682
CCDC
836065
836066
836067
Table 2. Geometrical parameters of hydrogen bonds in 3a, 3b and 3c compounds
Compound
D–H···A a
D···A (Å)
H···A (Å)
D–H···A (◦)
3a
Intra C9–H9···O3
Intra C15–H15···O1
C10–H10···O4
C16–H16···O1
O3–H3···O6
2.7061(19)
2.982(2)
2.7321(14)
2.9083(16)
2.661(6)
2.682(6)
3.269(9)
3.203(9)
2.913(7)
3.224(9)
3.224(8)
2.926(7)
2.34
2.37
2.35
2.26
1.84
1.86
2.51
2.53
2.26
2.42
2.54
2.27
103
123
104
126
173
176
139
130
127
144
131
127
3b
3c
O7–H7···O2
C4–H4···O7
C5–H5···O6
C15–H15···O1
C24–H24···O3
C25–H25···O2
C35–H35···O5
aAll of the C–H and O–H distances are neutron normalized to 1.083 and 0.983 Å.

88
D. Rambabu et al.
[27]. Table 1 gives the pertinent crystallographic data, and Table 2 gives hydrogen bond
parameters.
Results and Discussion
Aldol type condensation of benzofuran-3(2H)-one derivatives 1a–c with suitably substi-
tuted benzaldehyde derivatives 2a–c in the presence of ethylenediamine diacetate (EDDA)
in acetonitrile provided the corresponding products 3a–c in good yields (Schemes 2–4).
Scheme 2. Synthetic route for compound 3a.
Scheme 3. Synthetic route for compound 3b.
Scheme 4. Synthetic route for compound 3c.
Infrared Spectroscopy Analysis
Infrared (IR) spectra of the compounds 3a–c are given in supplementary material (see
Figs. S1–S3). The IR spectrum of synthesized aurones (3a–c) showed two absorptions in
the regions at 1670–1698 and 1635–1649 cm−1 due to the presence of α, β–unsaturated
system.

2-Benzylidenebenzofuran-3-(2H)-Ones
89
NMR Spectroscopy
1H and 13CNMR spectra of the compounds 3a–c are given in supplementary material
(see Figs. S4–S9). It is known from the literature that the assignment of configuration in
aurones is possible on the basis of the chemical shifts of the vinylic proton. The synthesized
compounds (3a–c) 1H NMR data also reveal that the vinylic proton in the structures shows
siglets δ 7.51, 7.54, and 6.76 ppm, respectively. The 13C NMR data also reveal that the
carbonyl absorption shows region δ 184.7, 184.7, and 181.1 ppm, respectively. It is evident
from the spectral data that a single geometric isomer (Z) was obtained in all these cases. The
Z-isomer is known to be thermodynamically more stable than E-isomer and the Z-aurones
could be photoisomerized to E-isomers.17 While the geometry of the double bond could be
established on the basis of chemical shift value (δ) of the vinylic proton as well as carbon
1
observed in the corresponding H and 13C NMR spectra [17, 28, 29], we however used
X-ray single crystal study of a representative compounds to establish its molecular structure
unambiguously.
High Resolution Mass Spectra (HRMS)
HRMS spectra of the compounds 3a–c are given in supplementary material (see Fig.
S10–S12) and confirm the molecular weights of the compounds.
Crystal Structure Analysis
2-(2-(3-methylbut-2-enyloxy)benzylidene)benzofuran-3(2H)-one, (3a). With regard to
crystal structure of compound 3a, it crystallizes in the cetrosymmetric space group P-1
with one molecule in the asymmetric unit (Zꢀ = 1) (Fig. 1). The molecular structure shows
that the enyloxybenzylidene moiety is not essentially coplanar with the benzofuranone moi-
ety (torsion angle of C1 C9 C10 C11 is 166.62◦). In the crystal structure, the molecules
form 1D tape-like structure. The C H group of benzofuranone moiety of one molecule
interacts with the translation-related C O group of another benzofuranone moiety of an-
other molecule via C H···O hydrogen bonding and form a 1D tape-like structure along
Figure 1. ORTEP representation of the compound 3a. Thermal ellipsoids are drawn at 50% proba-
bility level.

90
D. Rambabu et al.
Figure 2. Packing diagram of the compound 3a. 1D tape like structure along the crystallographic
a-axis with C–H···O hydrogen bonding.
the crystallographic a-axis (Fig. 2). These 1D tapes are further stabilized by bifurcated
C H···O hydrogen bonds. The inversion-related 1D tapes are further stabilized by weak
C H···π interactions.
2-(2-(allyloxy)benzylidene)-7-methoxybenzofuran-3(2H)-one, (3b). The compound 3b
crysatallizes in the orthorhombic Pbcn space group with one molecule in the asymmetric
unit (Zꢀ = 1) (Fig. 3). The molecular structure shows that the allyloxybenzylidene moi-
ety is not essentially coplanar with the methoxybenzofuranone moiety (torsion angle of
C1 C10 C11 C12 is 171.26◦). The methoxy group on benzofuranone is coplanar with
the benzofuranone moiety. The crystal structure analysis shows that the molecules form a
close packed structure. The two inversion-related molecules interact via C H···O dimer
synthons and these dimers are futher connected by interacting with methoxy oxygen and
methoxy methyl C H groups to form C H···O hydrogen bonds resulting in a 1D tape-like
structure (Fig. 4). These 1D tapes are further connected by several C H···O hydrogen
bonds and form a close packed structure.
Figure 3. ORTEP representation of the compound 3b. Thermal ellipsoids are drawn at 50% proba-
bility level.

2-Benzylidenebenzofuran-3-(2H)-Ones
91
Figure 4. Packing diagram of the compound 3b. 1D tape like structure along the crystallographic
c-axis with C–H···O hydrogen bonding.
2-(5-Bromo-2-(3-methylbut-2-enyloxy)benzylidene)-6-hydroxybenzofuran-3(2H)-one,
(3c). The compound 3c crystallizes in the orthorhombic chiral P212121 space group with
crystallographically two symmetry independent molecules in the asymmetric unit (Zꢀ =
2) (Fig. 5). The two molecules in the asymmetric unit are conformational isomers [30]
and an overlay diagram of the two conformers is shown in Fig. 6. The torsion angles of
3-methylbut-2-enyloxybenzylidene (O4–C16–C17–C18 and O8–C36–C37–C38) in the
two conformers are −119.37◦ and 124.88◦. These two molecules form layered structure in
the crystal. The O–H group of the hydroxybenzofuran moiety interacts with C O group
of the hydroxybenzofuranone moiety of another molecule via O–H···O hydrogen bonds
to form a 1D tape-like structure along the crystallographic a-axis. These 1D tapes further
Figure 5. ORTEP representation of the compound 3c. Thermal ellipsoids are drawn at 50% proba-
bility level.

92
D. Rambabu et al.
Figure 6. Overlay diagram of the two conformational isomers present in the asymmetric unit of the
compound 3c.
Figure 7. Packing diagram of the compound 3c. Layered structure along the crystallographic a-axis
with O–H···O and C–H···O hydrogen bonding.

2-Benzylidenebenzofuran-3-(2H)-Ones
93
propagate in (010) plane and form a layered structure (Fig. 7). These layers are further
stabilized by C–H···O hydrogen bonds.
Conclusions
The three derivatives of 2-benzylidenebenzofuran-3-(2H)-ones were synthesized and char-
acterized by spectral data. The structures of three compounds 3a–c were determined by
single crystal X-ray diffraction method. The geometrical configuration of all the compounds
3a–c was confirmed as Z. The crystal structure analysis shows that the compounds 3a and
3b form 1D tapes, whereas 3c forms a layered structure. Crystals of compound 3c have
two conformers in the asymmetric unit. The evaluation of biological activities of these
compounds is in progress.
Acknowledgments
DRB thanks Prof. Javed Iqbal, Director of ILS for his continuous support and encourage-
ments.
References
[1] Harborne, J. B. (1988). Prog. Clin. Biol. Res., 17, 280.
[2] Huang, W., Liu, M. Z., Li, Y., Tan, Y., & Yang, G. F. (2007). Bioorg. Med. Chem., 15, 5191.
[3] Morimoto, M., Fukumoto, H., Nozoe, T., Hagiwara, A., & Komai, K. (2007). J. Agric Food
Chem., 55, 700.
[4] Kayser, O., Kiderlen, A. F., Folkens, U., & Kolodziej, H. (1999) Planta Med. 65, 316.
[5] Souard, F., Okombi, S., Beney, C., Chevalley, S., Valentin, A., & Boumendjel, A. (2010). Bioorg
Med. Chem., 1, 5724.
[6] (a) Wang, J., Wang, N., Yao, X., & Kitanaka, S. (2007). J. Trad. Med., 2, 23. (b) Brooks, C. J.,
Watson, D. G. (1985). Phytoalexins. Nat. Prod. Rep., 2, 427.
[7] Okombi, S., Rival, D., Bonnet, S., Mariotte, A., Perrier, E., & Boumendjel, A. (2006). J. Med.
Chem., 49, 329.
[8] Aufmkolk, M., Koerhle, J., Hesch, R. D., & Cody, V. (1986). J. Biol. Chem., 261, 11623.
[9] Sheng, R., Xu, Y., Hu, C., Zhang, J., Lin, X., & Li, J. (2009). Eur. J. Med. Chem., 44, 7.
[10] Detsi, A., Majdalani, M., Kontogiorgis, C. A., Hadjipavlou-Litina, D., & Kefalas, P. (2009).
Bioorg. Med. Chem., 17, 8073.
[11] Mc Clure, J. W., Harbone, J. B., & Mabry, T. J. (1975). The Flavonoids, Chapman and Hall:
London.
[12] (a) Wilson, W. I., & Greenberg, B. M. (1993). Photochem. Photobiol., 53, 845. (b) Shanker, N.,
Dilek, O., Mukherjee, K., McGee, D. W., & Bane, S. L. (2011). J. Fluoresc., 21, 2173.
[13] Sanz, M., Simon, B. F., Esteruelas, E., MaMunoz, A., Cadah´ıa, E., Hernandez, T., Estrella, I.,
& Pinto, E. (2011). J. Agric. Food Chem., 59, 3135.
[14] Varma, R. S., & Varma, M. (1992). Tetrahedron Lett., 33, 5937.
[15] (a) Schoepfer, J., Fretz, H., Chaudhuri, B., Muller, L., Seeber, E., Meijer, L., Lozach, O.,
Vangrevelinghe, E., & Furet, P. (2002). J. Med. Chem., 45, 1741. (b) Lawrence, N. J., Rennison,
D., McGown, A. T., & Hadfield, J. A. (2003). Bioorg. Med. Chem. Lett., 13, 3759. (c) Okombi,
S., Rival, D., Bonnet, S., Mariotte, A. M., Perrier, E., & Boumendjel, A. (2006). J. Med. Chem.,
49, 329. (d) Morimoto, M., Fukumoto, H., Nozoe, T., Hagiwara, A., & Komai, K. (2007). J.
Agric. Food Chem., 55, 700. (e) Lee, C. Y., Chew, E. H., & Go, M. L. (2010). Eur. J. Med.
Chem., 45, 2957. (f) Haudecoeur, R., Ahmed-Belkacem, A., Yi, W., Fortune´, A., Brillet, R.,
Belle, C., Nicolle, E., Pallier, C., Pawlotsky, J. M., & Boumendjel, A. (2011). J. Med. Chem.,
54, 5395.

94
D. Rambabu et al.
[16] (a) Detsi, A., Majdalani, M., Kontogiorgis, C. A., Dimitra, H.-L., & Kefalas, P. (2009). Bioorg.
Med. Chem., 17, 8073. (b) Thakkar, K., & Cushman, M. (1995). J. Org. Chem., 60, 6499.
[17] (a) Venkateswarlu, S., Panchagnula, G. K., Gottumukkala, A. L., & Subbaraju, G. V. (2007).
Tetrahedron, 63, 6909. (b) Hastings, J. S., & Heller, H. G. (1972). J. Chem. Soc., Perkin Trans.
1, 2128.
[18] Bose, G., Mondal, E., Khan, A. T., & Bordoloi, M. J. (2001). Tetrahedron Lett., 42, 8907.
[19] Harkat, H., Blanc, A., Weibel, J. M., & Pale, P. (2008). J. Org. Chem., 73, 1620.
[20] Dean, F. M., & Podimuang, V. (1965). J. Chem. Soc., 3978.
[21] Atta-Ur-Rahman, Choudhary, M. I., Hayat, S., Khan, A. M., & Ahmed, A. (2001). Chem.
Pharm. Bull., 49, 105.
[22] Dewar, M. J. S., Zoebisch, E. G., Healy, E. F., & Stewart, J. J. P. (1985). J. Am. Chem. Soc.,
107, 3902.
[23] Zimmerman, H. E., & Ahramjian, L. (1959). J. Am. Chem. Soc., 81, 2086.
[24] (a) Beney, C., Mariotte, A. M., & Boumendjel, A. (2001). Heterocycles, 55, 967. (b) Khalil, N.
S. (2010). Eur. J. Med. Chem., 45, 5265. (c) Tyrrell, E., Tesfa, K. H., Millet, J., & Muller, C.
(2006). Synthesis, 18, 3099.
[25] SHELXTL. (2000). Program for the Solution and Refinement of Crystal Structures, (version
6.14), Bruker AXS: Wisconsin, USA.
[26] Sheldrick, G. M. (1997). SHELX-97: Program for the Solution and Refinement of Crystal
Structures, University of Go¨ttingen: Germany.
[27] (a) Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E.,
Rodriguez-Monge, L., Taylor, R., van de Streek, J., & Wood, P. A. (2008). J. Appl. Cryst., 41, 466.
(b) Burnett, M. N., & Johnson, C. K. (1996). ORTEPIII, Report ORNL-6895, Oak Ridge National
Laboratory: Tennessee, USA; Farrugia, L. J. (1997). J. Appl. Cryst., 30, 565. (c) Barbour, L.
J. (2001). X-Seed-A software tool for supramolecular crystallography. J. Supramol. Chem., 1,
189.
[28] Pelter, A., Ward, R. S., & Heller, H. G. (1979). J. Chem. Soc., Perkin Trans. 1, 328.
[29] Gray, T. I., Pelter, A., & Ward, R. S. (1979). Tetrahedron, 35, 2539.
[30] Rambabu, D., Krishna, G. R. Basavoju, S., Rao, M. V. B., Reddy, C. M., & Pal, M. (2012). J.
Mol. Struct., 1016, 126.