Synthesis, characterization and DFT study of 4H-benzo[h]chromene derivatives

Article abstract of DOI:10.1016/j.molstruc.2012.03.018

Interaction of 4-methoxy-1-naphthol (1) with α-cyano-p- chlorocinnamonitrile (2a) and ethyl α-cyano-p-chlorocinnamate (2b) provided 2-amino-4-(4-chlorophenyl)-6-methoxy-4H-benzo[h]chromene-3-carbonitrile (3a) and ethyl 2-amino-4-(4-chlorophenyl)-6-methoxy

Full text of DOI:10.1016/j.molstruc.2012.03.018

Journal of Molecular Structure 1018 (2012) 171–175
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, characterization and DFT study of 4H-benzo[h]chromene derivatives
⇑
⇑
Abdullah G. Al-Sehemi , Ahmad Irfan , Ahmed M. El-Agrody
Chemistry Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
Interaction of 4-methoxy-1-naphthol (1) with a-cyano-p-chlorocinnamonitrile (2a) and ethyl a-cyano-p-
Received 19 January 2012
Received in revised form 8 March 2012
Accepted 9 March 2012
chlorocinnamate (2b) provided 2-amino-4-(4-chlorophenyl)-6-methoxy-4H-benzo[h]chromene-3-car-
bonitrile (3a) and ethyl 2-amino-4-(4-chlorophenyl)-6-methoxy-4H-benzo[h]chromene-3-carboxylate
(3b), respectively. Structures of these compounds were established on the basis of IR, UV, 1H NMR, 13C
Available online 16 March 2012
13
NMR, C NMR-DEPT and MS data. Moreover, imino tautomer (3b0) has been designed. Using density
functional theory geometries have been optimized at B3LYP/6-31Gꢀ level of theory, the absorption spec-
tra has been computed by using time dependant density functional theory at TD-B3LYP/6-31Gꢀ level of
theory. Moreover, the absorption spectra in solvents have been computed and compared with experi-
mental data. The highest occupied molecular orbitals, lowest unoccupied molecular orbitals and
HOMO–LUMO energy gap of studied systems have been discussed.
Keywords:
4-Methoxy-1-naphthol
a
-Cyano-p-chlorocinnamonitrile
Ethyl -cyano-p-chlorocinnamate
a
4H-benzo[h]chromene
Ó 2012 Elsevier B.V. All rights reserved.
Density functional theory
1. Introduction
amino form and imino form; it was esteemed that imino form
would be good as biologically active molecule. Then we have com-
4H-Chromenes and fused 4H-chromenes nuclei are often found
in biologically active molecules and are widely used as antimicro-
bial and antifungal [1], antioxidant [2], antileishmanial [3], antitu-
mor [4], hypotensive [5], antiproliferation [6], central nervous
system (CNS) activities and effects [7] as well as treatment of
Alzheimer’s disease [8] and Schizophrenia disorder [9]. In addition
they function as inhibitors of influenza virus sialidases [10]. They
exhibit anti-inflammatory [11], DNA stand-breaking, mutagenic
[12], antiviral [13] anticoagulant [14] and analgesic activities [15]
and also act as sex pheromone homologues [16].
pared the properties with 3b. Moreover, the effect of NH2 and NH
at position 2 in 3b and 3b0 (Scheme 2) has been studied.
2. Experimental
Melting points were determined with a Stuart Scientific Co., Ltd.
apparatus. UV spectra were measured on a Shimadzu UV-160 1PC
UV–Vis spectrophotometer. IR spectra were determined as KBr pel-
lets on a Jasco FT/IR 460 plus spectrophotometer. 1H NMR and 13
C
NMR spectra were recorded using a Bruker AV 500 MHz spectrom-
eter. 13C NMR spectra were obtained using distortionless enhance-
ment by polarization transfer (DEPT), with this technique, the
signals from CH and CH3 carbons were positive (up) whilst signals
from CH2 environments are negative (down). Mass spectra were
measured on a Shimadzu GC/MS-QP5050A spectrometer. Elemen-
tal analyses were performed on a Perkin–Elmer 240 microanalyser
in the Faculty of Science Cairo University.
In continuation of the previous works [17], it seemed interest-
ing to synthesize novel 4H-benzo[h]chromene compounds using
a
-cyanocinnamonitriles and ethyl
ment of 4-methoxy-1-naphthol (1) with
monitrile (2a) and ethyl -cyano-p-chlorocinnamate (2b) in
a
-cyanocinnamates. Thus, treat-
a-cyano-p-chlorocinna-
a
ethanol and piperidine under reflux afforded 2-amino-4-(4-chloro-
phenyl)-6-methoxy-4H-benzo[h]chromene-3-carbonitrile (3a) and
ethyl 2-amino-4-(4-chlorophenyl)-6-methoxy-4H-benzo[h]chro-
mene-3-carboxylate (3b) respectively (Scheme 1). Structures were
established on the basis of IR, UV, 1H NMR, 13C NMR, 13C NMR-
DEPT and MS data.
2.1. Reaction of 4-methoxy-1-naphthol (1) with 2a,b
By applying DFT and TDDFT theories we shed light on the geom-
etries, electronic and optical properties. The structure–property
relationship has been intensively investigated. The compound
which we have studied 3b have two possibilities, two tautomer
2.1.1. General procedure
A solution of 4-methoxy-1-naphthol (1) (0.01 mmol) in EtOH
(30 mL) was treated with
a-cyano-p-chlorocinnamonitrile (2a) or
ethyl -cyano-p-chlorocinnamate (2b) (0.01 mmol) and piperidine
a
(0.5 mL). The reaction mixture was heated until complete precipi-
tation occurred (reaction times: 60 min for 2a; 120 min for 2b).
The solid product which formed was collected by filtration and
recrystallied from ethanol to give 3a,b. The physical and spectral
⇑
Corresponding authors. Tel.: +966 72418632; fax: +966 72418426.
E-mail addresses: agmasq@gmail.com (A.G. Al-Sehemi), irfaahmad@gmail.com
(A. Irfan).
0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2012.03.018

172
A.G. Al-Sehemi et al. / Journal of Molecular Structure 1018 (2012) 171–175
9
positive) revealed signals at d 129.39 (CH " aromatic), 128.67 (CH
10
8
7
" aromatic), 127.30 (C-9 "), 126.31 (C-8 "), 121.65 (C-7 "), 120.61
(C-10 "), 103.27 (C-5 "), 55.73 (CH3 "), 40.74 (C-4 "); MS m/z (%):
364 (M++2, 4.31), 362 (M+, 18.7), 251 (82), 236 (20), 208 (27),
180 (36), 151 (43), 111 (43), 75 (100), 50 (45) C21H15ClN2O2.
1
O
2
3
NH
X
2
OH
6a
pip.
EtOH /
reflux
CN
X
MeO
4a
6
+
Ar-
CH=C
4
5
Ar
1
3a,b
2a,b
OMe
2.1.3. Ethyl 2-amino-4-(4-chlorophenyl)-6-methoxy-4H-
benzo[h]chromene-3-carboxylate (3b)
a; Ar = p-ClC H
X= CN
X= CO Et
6
6
4
4
b; Ar = p-ClC H
2
Colourless crystals from ethanol; m.p. 160–161 °C; 87%; UV–Vis
(THF): 250 nm; IR (KBr)
t
(cmꢁ1): 3406, 3330 (NH2), 3030, 3010,
Scheme 1. Schematic diagram of the new synthesized 4H-benzo[h]chromene
derivatives.
2981, 2938, 2899 (CH stretching), 1666 (CO); 1H NMR (500 MHz)
(CDCl3) d: 8.10–6.27 (m, 9H, aromatic), 6.30 (bs, 2H, NH2, cancelled
by D2O), 4.91 (s, 1H, H-4), 4.02 (q, 2H, CH2, J = 7.5 Hz), 3.78 (s, 3H,
OCH3), 1.13 (t, 3H, CH3, J = 7.5 Hz); 13C NMR (125 MHz) (CDCl3) d:
168.08 (CO), 161.09 (C-2), 151.18 (C-6), 146.58 (C-10b), 128.30 (C-
10a), 127.07 (C-9), 125.93 (C-8), 124.18 (C-6a), 121.62 (C-7),
120.59 (C-10), 120.36 (C-4a), 103.79 (C-5), 76.00 (C-3), 58.62
(CH2), 55.72 (CH3), 40.08 (C-4), 14.30 (CH3), 136.90, 130.53,
129.13, 128.14 (aromatic); 13C NMR-DEPT spectrum at 135° CH,
CH3 [positive (up)], CH2 [negative (down)], revealed the following
signals at d 129.13 (CH " aromatic), 128.14 (CH " aromatic),
127.07 (C-9 "), 125.93 (C-8 "), 121.62 (C-7 "), 120.59 (C-10 "),
103.79 (C-5 "), 58.62 (CH2 ;), 55.72 (CH3 "), 40.08 (C-4 "), 14.30
(CH3 "). In the DEPT spectrum at 90° only CH signals are positive
(up) and showed d 127.07 (C-9 "), 125.93 (C-8 "), 121.62 (C-7 "),
120.59 (C-10 "), 103.79 (C-5 "), 40.08 (C-4"). In the DEPT spectrum
at 45° (CH, CH2 and CH3 positive) revealed signals at d 127.07 (C-9
"), 125.93 (C-8 "), 121.62 (C-7 "), 120.59 (C-10 "), 103.79 (C-5 "),
58.62 (CH2 "), 55.72 (CH3 "), 40.08 (C-4"), 14.30 (CH3 "); MS m/z
(%): 411 (M++2, 5.31), 409 (M+, 19.38), 298 (91), 270 (15), 226
(19), 198 (4), 164 (14), 111 (51), 75 (100), 50 (46) C23H20ClNO4.
9
9
8
7
10
H
N H
10
8
7
1
1
O
2
3
O
2
3
NH
6a
6a
MeO
CO2Et
6
4a
MeO
4a
CO2Et
6
4
5
4
5
Ar
Ar
3b
Ar = p-ClC6H4
3b'
Scheme 2. Schematic diagram of the 3b and 3b0 with labeling.
data of compounds 3a,b are as follows: It should be added that
spectra of 3a and 3b were recorded in THF in Table 1, as well as
in the experimental part.
2.1.2. 2-Amino-4-(4-chlorophenyl)-6-methoxy-4H-
benzo[h]chromene-3-carbonitrile (3a)
Colourless needles from ethanol; m.p. 218–219 °C; UV–Vis
(THF): 248 nm; 89%; IR (KBr)
t
(cmꢁ1): 3466, 3330, 3199 (NH2),
3080, 3000, 2962, 2810 (CH stretching), 2194 (CN); 1H NMR
(500 MHz) (DMSO-d6) d: 8.21–6.52 (m, 9H, aromatic), 7.15 (bs,
2H, NH2, cancelled by D2O), 4.89 (s, 1H, H-4), 3.81 (s, 3H, OCH3);
13C NMR (125 MHz) (DMSO-d6) d: 160.41 (C-2), 151.23 (C-6),
144.47 (C-10b), 131.48 (C-10a), 127.30 (C-9), 126.31 (C-8),
123.62 (C-6a), 121.65 (C-7), 120.61 (C-10), 120.48 (C-4a), 117.27
(CN), 103.27 (C-5), 55.72 (C-3), 55.73 (CH3), 40.74 (C-4), 136.87,
129.39, 128.67, 124.43 (aromatic); 13C NMR-DEPT spectrum at
135° CH, CH3 [positive (up)], CH2 [negative (down)], revealed the
following signals at d 129.39 (CH " aromatic), 128.67 (CH "
aromatic), 127.30 (C-9 "), 126.31 (C-8 "), 121.65 (C-7 "), 120.61
(C-10 "), 103.27 (C-5 "), 55.73 (CH3 "), 40.74 (C-4 "). In the DEPT
spectrum at 90° only CH signals are positive (up) and showed d
129.39 (CH" aromatic), 128.67 (CH " aromatic), 127.30 (C-9 "),
126.31 (C-8 "), 121.65 (C-7 "), 120.61 (C-10 "), 103.27 (C-5 "),
40.74 (C-4 "). In the DEPT spectrum at 45° (CH, CH2 and CH3
3. Computational detail
The computations of the geometries, electronic structures, as
well as electronic absorption spectra were performed using density
functional theory (DFT) and time dependant density functional
theory (TDDFT), respectively with Gaussian09 package [18]. The
DFT was treated according to Becke’s three parameter gradient-
corrected exchange potential and the Lee–Yang–Parr gradient-cor-
rected correlation potential (B3LYP) [19–21], and all calculations
were performed by using 6-31Gꢀ basis set [22]. The TDDFT has
been used to investigate the absorption spectra which have been
proved an efficient approach [23,24]. The polarizable continuum
model (PCM) [25,26] is used for evaluating bulk solvent effects at
all stages. The PCM-TDB3LYP/6-31Gꢀ level of theory has been used
to compute the absorption spectra in THF and methanol.
4. Result and discussion
Table 1
Optimized geometrical parameters of investigated systems at B3LYP/6-31Gꢀ level of
theory.
Structure of 3 was established on the basis of spectral data. The
IR spectrum of 3a showed the presence of a NH2 bands at
3330, 3199 cmꢁ1 and a CN band at 2194 cmꢁ1, while for 3b
showed the appearance of a NH2 bands at
3406, 3299 cmꢁ1
and a CO band at
1666 cmꢁ1 (see Supporting information). The
UV spectra of 3a,b revealed a weak shoulder characteristic for
4H-chromene [43–45,48] at kmax (THF) 420–406 nm (log 2.71–
t 3466,
3a
3b
3b0
t
t
Bond lengths (Å)
O1–C2
C2–C3
C3–C4
C4–C4a
1.352
1.366
1.522
1.520
1.533
1.357
1.376
1.520
1.520
1.535
1.366
t
1.517
1.554
1.520
1.525
e
1.52). The 1H and 13C NMR spectra of 3a showed signals at d 7.15
(bs, 2H, NH2, cancelled by D2O), 4.89 (s, 1H, H-4) and 40.76 ppm
(C-4). In compound 3b the amino group gave 1H signals at 6.27
(bs, 2H, NH2, cancelled by D2O) and the ester group at 4.02 (q,
2H, CH2, J = 7.5 Hz) and 1.13 ppm (t, 3H, CH3, J = 7.5 Hz) with the
corresponding signals in the 13C spectrum at 59.54 and
14.41 ppm respectively. The 13C NMR-DEPT spectra at 45°, 90°
C4–C4b
Bond angles (°)
O1–C2–C3
C2–C3–C4
C3–C4–C4a
C3–C4–C4b
C4a–C4–C4b
1.352
1.366
1.522
1.520
1.533
122.95
120.83
110.31
113.05
110.93
117.30
112.68
109.97
110.00
113.99

A.G. Al-Sehemi et al. / Journal of Molecular Structure 1018 (2012) 171–175
173
and 135° and mass spectra of compounds 3a, 3b provided addi-
tional evidence in support of the proposed structures.
the studied systems in the S0 states have been shown in Fig. 2
which suggests the delocalization and localization of molecular
orbitals. It can be seen that HOMOs are located on the 4H-
benzo[h]chromene, oxygens of methoxy and CO2Et also take part
in the formation of HOMO. The LUMO is localized on whole of
the system, the nitrogen of NH2 also participate in the formation
4.1. Geometries
In Table 1 we gave selected geometrical parameters of the 3a,
3b and 3b0. The effect of CN and CO2Et has been studied on the geo-
metrical parameters. Maximum lengthening or shortening in the
bond lengths has been described here. Here we will compare
lengthening and shortening of bond lengths by comparing to 3a.
The calculated bond length of O1–C2 is lengthened 0.005 and
0.014 Å in 3b and 3b0, respectively compared to 3a. The bond
length C2–C3 lengthened 0.010 and 0.151 Å in 3b, and 3b0, respec-
tively compared to 3a. The increase has been observed 0.032 Å in
C3–C4 while decrease in C4–C4b to be 0.008 Å in 3b0. The negligible
deviation has been found for other bond lengths. The lengthening
or shortening of bond length is due to the electronic density local-
ized on nearest atom. By introducing strong electron withdrawing
groups (EWDGs) at X, the significant effect observed for C2–C3
which increases because EWDGs attract the electrons toward itself
and decreases the electronic density on C2 resulting increase of the
C2–C3 bond length as in 3b and 3b0. The significant increase or
decrease in bond angles has been observed in 3b0, e.g. O1–C2–C3,
C2–C3–C4, and C3–C4–C4b are 5.91°, 9.66° and 2.49° larger while
C4a–C4–C4b is shorter 2.27° compared to 3a. The O1–C2–C3,
C2–C3–C4 and C4a–C4–C4b are smaller 0.26°, 1.83°, and 1.35°
while C3–C4–C4a, and C3–C4–C4b larger 0.72° and 0.56° than 3a.
The optimized structure information of 3b and 3b0 is shown in
Fig. 1 along with the relative energies. The most stable tautomer
corresponds to the amino-form structure 3b which is in good
agreement with the experimental evidence. The energies com-
puted at the B3LYP/6-31Gꢀ level of theory revealed that 3b has
14.68 kcal/mol less energy than 3b0 which leads toward higher
HOMO, lower LUMO and smaller HOMO–LUMO energy gap. As
3b has 14.68 kcal/mol less energy than 3b0 due to which it is more
stable tautomer. Moreover, hydrogen bond in water is 1.97 Å [27],
in amino form (3b) the hydrogen bond is 1.896 Å, see Fig. 1 which
stabilize this tautomer compared to imino form.
of LUMO. The tendency of HOMO energies (EHOMO
)
is
3b > 3b0 > 3a while in LUMO energies (ELUMO) 3b0 > 3a > 3b. The
trend of gap energies (Egap) is 3b > 3b0 = 3a, see Table 2.
4.3. Absorption spectra
In Table 3, we have reported the calculated and experimental
absorption spectra. The 3b and 3b0 showed blue shifts in absorp-
tion spectra ca. 46 and 70 nm, respectively compared with 3a with-
out considering any solvent. The 3b and 3b0 showed 42 and 64 nm
blue shifts, respectively compared with 3a in methanol. Experi-
mental absorption spectrum of 3b is 2 nm red shifted than 3a in
THF. It was found 2 nm red shift in 3b and 17 nm blue shift in
3b0 in THF compared to 3a at TD-B3LYP/6-31Gꢀ level of theory.
The experimental absorption spectra are well reproduced by our
adopted theoretical approach; absorption spectra computed in
THF. Generally, the absorption spectra overestimated in methanol
and without any solvent. The absorption spectrum of 3a in metha-
nol is 293 nm which is 7 nm blue shifted than the absorption spec-
trum of the same system without considering solvent. The three
absorption peaks have been observed for experimental absorption
wavelengths of 3a and 3b. The 3a showed peaks at 248, 283 and
331 nm in THF while for 3b peaks are dominated at 250, 284 and
332 nm. The computed absorption spectra in THF are in good
agreement with the experimental data reproducing three absorp-
tion peaks in the same wavelengths. The assignments for the
absorption are HOMO to LUMO. The ground state dipole moment
(l) values for all the compounds studied in this work, computed
at the B3LYP/6-31Gꢀ level of theory are given in Table 3. The high-
est dipole moment has been observed in 3a having CN at position 3
while the smallest for 3b. In our previous study [28], we explained
that ‘‘NH2, CH3, CN, Cl’’ substitution affect dipole moment depen-
dently on the substituted group and position. The same effect
has been observed here that electron donating group NH2 at posi-
tion 2 and CN on position 3 leads to higher dipole moment.
Major contribution of different frontier molecular orbitals has
been presented in Supporting information, see contribution section.
4.2. Electronic structure
The distribution pattern of highest occupied molecular orbitals
(HOMOs) and lowest unoccupied molecular orbitals (LUMOs) of
Fig. 1. The optimized geometries of the amino and imino forms of compound 3.

174
A.G. Al-Sehemi et al. / Journal of Molecular Structure 1018 (2012) 171–175
Fig. 2. The distribution pattern of HOMOs and LUMOs of 3a, 3b and 3b0.
Table 2
81% contribution. The third state has 97% contribution from H-
1 ? LUMO transition. The fourth, fifth, sixth, seventh, eighth, and
ninth states are derived from H-1 ? L + 1, HOMO ? L + 2, H-
3 ? LUMO, H-2 ? LUMO, H-3 ? L + 1, and H-2 ? L + 1 transitions
with 89%, 60%, 45%, 56%, 53%, and 64% contribution, respectively.
In 3b the main transition is HOMO ? LUMO contributing 84% while
other major transitions are as follow: HOMO ? L + 1, HOMO-
HOMO energy (EHOMO), LUMO energy (ELUMO) and HOMO–LUMO energy gap (Egap) in
eV at B3LYP/6-31Gꢀ level of theory.
System
EHOMO
ELUMO
Egap
3a
3b
3b0
ꢁ5.59
ꢁ5.40
ꢁ5.52
ꢁ1.23
ꢁ1.40
ꢁ1.14
4.36
4.36
4.38
1 ? LUMO,
HOMO ? L + 2,
HOMO ? L + 3,
H-1 ? L + 1,
HOMO ? L + 4, H-2 ? LUMO, and H-1 ? L + 2 contributing 63%,
78%, 67%, 52%, 76%, 86%, 65% and 72% for first to ninth states,
respectively. In 3b0, S0-S1 state remains dominated with maximum
absorption and this state is caused by HOMO ? LUMO transition
with 96% contribution. The second state caused by HOMO ? L + 1
transition with 70% contribution. The third state has 73% contribu-
tion from HOMO ? L + 2 transition. The fourth, fifth, sixth, seventh,
eighth, and ninth states are derived from HOMO ? L + 3,
HOMO ? L + 4, HOMO ? L + 5, H-1 ? LUMO, H-1 ? L + 1, and H-
1 ? L + 1 transitions with 77%, 75%, 79%, 45%, 40%, and 29% contri-
bution, respectively, see Supporting information.
Table 3
Calculateda,b,c and experimentald absorption wavelengths (ka) in nm and dipole
moment (
l
) of 3a, 3b and 3b0.
a
b
c
d
Systems
Assignments
ka
ka
ka
ka
l
3a
H ? L
300
400
293
398
250
288
326
248
283
331
5.36
3b
H ? L
H ? L
254
294
325
251
294
327
252
294
327
250
284
332
3.16
4.39
3b0
230
315
229
305
233
305
5. Conclusions
a
b
c
The calculated absorption wavelengths at TD-B3LYP/6-31G* without solvent.
The calculated absorption wavelengths at TD-B3LYP/6-31G* in methanol.
The calculated absorption wavelengths at TD-B3LYP/6-31G* in THF.
The experimental absorption wavelengths in THF.
The IR spectrum of 3a showed the presence of a NH2 bands at
3466, 3330, 3199 cmꢁ1 and a CN band at 2194 cmꢁ1, while for 3b
showed the appearance of a NH2 bands at
3406, 3299 cmꢁ1 and a
CO band at
1666 cmꢁ1. The major change in bond lengths has
t
d
t
t
t
In 3a, S0-S1 state remains dominated with maximum absorption
and this state is caused by HOMO ? LUMO transition with 94% con-
tribution. The second state caused by HOMO ? L + 1 transition with
been observed, where CN has been replaced by CO2Et and NH2
by NH. The lengthening or shortening of bond length is due to
the electronic density localized on nearest atom. By introducing

A.G. Al-Sehemi et al. / Journal of Molecular Structure 1018 (2012) 171–175
175
L.S. Sollis, D.P. Howes, C.P. Cherry, R. Bethell, P. Colman, J. Varghese, J. Med.
Chem. 41 (1998) 798.
[11] (a) J.-F. Cheng, A. Ishikawa, Y. Ono, T. Arrhenius, A. Nadzan, Bioorg. Med. Chem.
Lett. 13 (2003) 3647;
strong EWDGs at X, the significant effect observed for C2–C3 which
increases because EWDGs attract the electrons toward itself and
decreases the electronic density on C2 resulting increase the C2–
C3 bond length. The stable tautomer corresponds to the amino-
form structure 3b which is in good agreement with the experimen-
tal data. The HOMOs are delocalized on the 4H-benzo[h]chromene
while LUMOs are localized on whole of the system. The computed
absorption spectra in THF are in good agreement with the experi-
mental evidence. The highest dipole moment has been observed in
3a. In 3a, 3b and 3b0 S0–S1 state remains dominated with maxi-
mum absorption and these states are caused by HOMO ? LUMO
transition with 94%, 84% and 96% contribution, respectively.
(b) V.P. Sharma, Asian J. Chem. 16 (2004) 1966;
(c) V.P. Sharma, Indian J. Heterocycl. Chem. 14 (2004) 35;
(d) P. Gebhardt, K. Dornberger, F.A. Gollmick, U. Gräfe, A. Härtl, H. Görls, B.
Schlegel, C. Hertweck, Bioorg. Med. Chem. Lett. 17 (2007) 2558;
(e) G. Melagraki, A. Afantitis, O. Igglessi-Markopoulou, A. Detsi, M. Koufaki, C.
Kontogiorgis, D.J. Hadjipavlou-Litina, Eur. J. Med. Chem. 44 (2009) 3020;
(f) T. Symeonidis, K.C. Fylaktakidou, D.J. Hadjipavlou-Litina, K.E. Litinas, Eur. J.
Med. Chem. 44 (2009) 5012;
(g) S. Begum, B. Saxena, Ma. Goyal, R. Ranjan, V.B. Joshi, C.V. Rao, S.
Krishnamurthy, M. Sahai, Fitoterapia 81 (2010) 178;
(h) J.J. Anil, R.A. Kumar, S.A. Rasheed, S.P. Chandrika, A. Chandrasekhar, S. Baby,
A. Subramoniam, J. Ethnopharm. 130 (2010) 267.
[12] K. Hiramoto, A. Nasuhara, K. Michiloshi, T. Kato, K. Kikugawa, Mutat. Res. 395
(1997) 47.
[13] A.G. Martinez, L.J. Marco, Bioorg. Med. Chem. Lett. 7 (1997) 3165.
[14] (a) W.O. Foye, Principi Di Chimica Farmaceutica; Piccin: Padova, Italy (1991)
416;
Acknowledgement
We are thankful to the King Khalid University for the facilities
and support to carry out the research.
(b) L. Bonsignore, G. Loy, D. Secci, A. Calignano, Eur. J. Med. Chem. 28 (1993)
517.
[15] (a) A. Gajbhiye, V. Mallareddy, G. Achaiah, Indian J. Pharm. Sci. 70 (2008) 118;
(b) M. Ghate, R.A. Kusanur, M.V. Kulkarni, Eur. J. Med. Chem. 40 (2005) 882;
(c) T. El-Sayed Ali, M.A. Ibrahim, J. Braz. Chem. Soc. 21 (2010) 1007;
(d) B. Narasimhan, P. Kumar, D. Sharma, Acta Pharm. Sci. 52 (2010) 169;
(e) K.M. Amin, M.M. Kamel, M.M. Anwar, M. Khedr, Y.M. Syam, Eur. J. Med.
Chem. 45 (2010) 2117;
(f) R.S. Keri, K.M. Hosamani, R.V. Shingalapur, M.H. Hugar, Eur. J. Med. Chem.
45 (2010) 2597.
[16] G. Bianchi, A. Tava, Agric. Biol. Chem. 51 (1987) 2001.
[17] (a) A.M. El-Agrody, J. Chem. Res. (S) (1994) 280;
Appendix A. Supplementary material
Experimental UV–Vis spectra, IR spectra, NMR spectra and com-
puted states with contribution can be found in supporting informa-
tion. Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.molstruc. 2012.
03.018.
(b) A.M. El-Agrody, H.A. Emam, M.H. El-Hakim, M.S. Abd El-Latif, A.H. Fakery, J.
Chem. Res. (S) (1997) 320;
(c) A.M. El-Agrody, H.A. Emam, M.H. El-Hakim, M.S. Abd El-Latif, A.H. Fakery, J.
Chem. Res. (M) (1997) 2039;
References
(d) A.H. Bedair, N.A. El-Hady, M.S. Abd El-Latif, A.H. Fakery, A.M. El-Agrody, IL
Farmaco 55 (2000) 708;
(e) A.M. El-Agrody, M.H. El-Hakim, M.S. Abd El-Latif, A.H. Fakery, E.S.M. El-
Sayed, K.A. El-Ghareab, Acta Pharm. 50 (2000) 111;
(f) A.Z. Sayed, N.A. El-Hady, A.M. El-Agrody, J. Chem. Res. (S) (2000) 146;
(g) A.M. El-Agrody, M.S. Abd El-Latif, N.A. El-Hady, A.H. Fakery, A.H. Bedair,
Molecules 6 (2000) 519;
(h) A.H. Bedair, H.A. Emam, N.A. El-Hady, K.A.R. Ahmed, A.M. El-Agrody, IL
Farmaco 56 (2001) 965;
(i) A.M. El-Agrody, F.A. Eid, H.A. Emam, H.M. Mohamed, A.H. Bedair, Z.
Naturforsch, Teil B 57 (2002) 579;
(j) M.M. Khafagy, A.H.F. Abd El-Wahab, F.A. Eid, A.M. El-Agrody, IL Farmaco 57
(2002) 715;
(k) F.A. Eid, A.H. Bedair, H.A. Emam, H.M. Mohamed, A.M. El-Agrody, Al-Azhar
Bull. Sci. 14 (2003) 311;
(l) A.S. Abd-El-Aziz, A.M. El-Agrody, A.H. Bedair, T.C. Corkery, A. Ata,
Heterocycles 63 (2004) 1793;
[1] (a) A.M. El-Agrody, M.H. El-Hakium, M.S. Abd El-Latif, A.H. Fekry, E.S.M. El-
Sayed, K.A. El-Gareab, Acta Pharm. 50 (2000) 111;
(b) M.C. Yimdjo, A.G. Azebaze, A.E. Nkengfack, A. Michele Meyer, B. Bodo, Z.T.
Fomum, Phytochemistry 65 (2004) 2789;
(c) Z.Q. Xu, K. Pupek, W.J. Suling, L. Enache, M.T. Flavin, Bioorg. Med. Chem.
Lett. 14 (2006) 4610;
(d) V. Jeso, K.C. Nicolaou, Tetrahedron Lett. 50 (2009) 1161;
(e) L. Alvey, S. Prado, B. Saint-Joanis, S. Michel, M. Koch, S.T. Cole, F. Tillequin,
Y.L. Janin, Eur. J. Med. Chem. 44 (2009) 2497.
[2] (a) L. Alvey, S. Prado, V. Huteau, B. Saint-Joanis, S. Michel, M. Koch, S.T. Cole, F.
Tillequin, Y.L. Janin, Bioorg. Med. Chem. 16 (2008) 8264;
(b) T. Symeonidis, M. Chamilos, D.J. Hadjipavlou-Litina, M. Kallitsakis, K.E.
Litinas, Bioorg. Med. Chem. Lett. 19 (2009) 1139.
[3] (a) T. Narender, Shweta, S. Gupta, Bioorg. Med. Chem. Lett. 14 (2009) 3913;
(b) D.B. daSilva, E.C.O. Tulli, G.C.G. Militao, L.V. Costa-Lotufo, C. Pessoa, M.O. De
Moraes, S. Albuquerque, J.M. de Siqueira, Phytomedicine 70 (2009) 590;
(c) J.C.A. Tanaka, C.C. da Silva, I.C.P. Ferreira, G.M.C. Machado, L.L. Leon, A.J.B. de
Oliveira, Phytomedicine 14 (2007) 377;
(m) A.S. Abd-El-Aziz, H.M. Mohamed, S. Mohammed, S. Zahid, A. Ata, A.H.
Bedair, A.M. El-Agrody, P.D. Harvey, J. Heterocycl. Chem. 44 (2007) 1287;
(n) N.M. Sabry, H.M. Mohamed, E. Shawky, A.E.H. Khattab, S.S. Motlaq, A.M. El-
Agrody, Eur. J. Med. Chem. 46 (2011) 765;
(d) V. Lakshmi, K. Pandey, A. Kapil, N. Singh, M. Samant, A. Dube,
Phytomedicine 14 (2007) 36;
(e) E.C. Torres-Santos, D. Lopes, R. Rodrigues Oliveira, J.P.P. Carauta, C.A.
Bandeira, Falcao, M.A.C. Kaplan, B. Rossi-Bergmann, Phytomedicine 11 (2004)
114.
(o) A.M. El-Agrody, N.M. Sabry, S.S. Motlaq, J. Chem. Res. 35 (2011) 77.
[18] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato,
X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M.
Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery, Jr., J.E. Peralta, F. Ogliaro,
M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M.
Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo,
J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C.
Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth,
P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, Ö. Farkas, J.B. Foresman,
J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian, Gaussian 09, Revision A.1; Gaussian,
Inc., Wallingford, CT, 2009.
[4] (a) A. Rampa, A. Bisi, F. Belluti, S. Gobbi, L. Piazzi, P. Valenti, A. Zampiron, A.
Caputo, K. Varani, P.A. Borea, M. Carrara, IL Farmaco 60 (2005) 135;
(b) Q.-B. Han, N.-Y. Yang, H.-L. Tian, C.-F. Qiao, J.-Z. Song, D.C. Chang, S.-L. Chen,
K.Q. Luo, H.-X. Xu, Phytochemistry 69 (2008) 2187;
(c) W. Kemnitzer, J. Drewe, S. Jiang, H. Zhang, C. Crogan-Grundy, D. Labreque,
M. bubenick, G. Attardo, R. Denis, S. Lamothe, H. Gourdeau, B. Tseng, S.
Kasibhatla, S.X. Cai, J. Med. Chem. 51 (2008) 417.
[5] V.K. Tandon, M. Vaish, S. Jain, D.S. Bhakuni, R.C. Srimal, Indian J. Pharm. Sci. 53
(1991) 22.
[6] (a) M. Brunavs, C.P. Dell, P.T. Gallagher, W.M. Owton, C.M. Smith, Eur. Pat. Appl.
EP. 557 (1993) 075;
(b) M. Brunavs, C.P. Dell, P.T. Gallagher, W.M. Owton, C.M. Swith, Chem. Abstr.
120 (1994) 106768;
[19] A.D. Becke, J. Chem. Phys. 98 (1993) 5648.
[20] B. Miehlich, A. Savin, H. Stoll, H. Preuss, Chem. Phys. Lett. 157 (1989) 200.
[21] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
[22] J. Sun, J. Song, Y. Zhao, W.Z. Liang, J. Chem. Phys. 127 (2007) 234107.
[23] C.R. Zhang, W.Z. Liang, H.S. Chen, Y.H. Chen, Z.Q. Wei, Y.Z. Wu, J. Mol. Struct.
(THEOCHEM) 862 (2008) 98.
[24] D. Matthews, P. Infelta, M. Grätzel, Sol. Energy Mater. Sol. Cells 44 (1996) 119.
[25] M. Cossi, V. Barone, J. Chem. Phys. 115 (2001) 4708.
[26] C. Amovilli, V. Barone, R. Cammi, E. Cancès, M. Cossi, B. Mennucci, C.S. Pomelli,
J. Tomasi, Adv. Quant. Chem. 32 (1998) 227.
(c) V. Magedov, M. Manpadi, M.A. Ogasawara, A.S. Dhawan, S. Rogelj, S. van-
Slambrouk, W.F.A. Steelant, N.M. Evdokimov, P.Y. Uglinskii, E.M. Elias, E.J. Knee,
P. Tongwa, M.Yu. Antipin, A. Kornienko, J. Med. Chem. 51 (2008) 2561.
[7] F. Eiden, F. Denk, Arch. Pharm. Weinheim Ger. 324 (1991) 875.
[8] C. Bruhlmann, F. Ooms, P. Carrupt, B. Testa, M. Catto, F. Leonetti, C. Altomare, A.
Cartti, J. Med. Chem. 44 (2001) 3195.
[9] S.R. Kesten, T.G. Heffner, S.J. Johnson, T.A. Pugsley, J.L. Wright, D.L. Wise, J. Med.
Chem. 42 (1999) 3718.
[10] (a) W.P. Smith, L.S. Sollis, D.P. Howes, C.P. Cherry, D.I. Starkey, N.K. Cobley, J.
Med. Chem. 41 (1998) 787;
[27] J.R. Larson, J.W. Petrich, N.C. Yang, J. Am. Chem. Soc. 104 (1982) 5000–5002.
[28] A. Irfan, R. Cui, J. Zhang, L. Hao, Chem. Phys. 364 (2009) 39–45.
(b) R.N. Taylor, A. Cleasby, O. Singh, T. Sharzynski, J.A. Wonacott, W.P. Smith,