718
S. Elavarasan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 717–721
p
the
-system delocalization [5]. There is a strong correlation between
R5
O
O
R5
R2
p-system delocalization and the strengthening of the intra-
R4
R3
R4
R3
O
O
molecular hydrogen bond. Moreover, in solution curcumin can
form inter-molecular H-bonds with the solvent molecules and this
strongly influences its physicochemical properties. The chemopre-
ventive effects of curcumin have been attributed to various biolog-
ical properties, including neutralization of carcinogenic free
radicals [6] and anti-angiogenesis action, which limits the blood
supply to rapidly growing malignant cells [7,8]. However, the nat-
ure of many biological properties of curcumin remains unclear;
therefore the investigation of the structure and reactivity of this
prolific medicinal agent is important. A photolysis study by Jova-
novic et al. attributes the antioxidant mechanism of curcumin to
intramolecular H-atom in the keto-enolic group [9]. A theoretical
study by Balasubramanian suggests that the keto-enolic form of
curcumin may be responsible for the inhibition of b-amyloid
aggregation [10].
During the last decade, synthetic modifications of curcumin,
which were aimed at enhancing its bioactivities, have been inten-
sively studied. One sustainable strategy for green synthesis of or-
ganic compounds is microwave irradiation. Since, microwaves
will not affect molecular structure in the excitation of molecules,
the effect of microwave absorption is purely kinetic. Compared to
traditional methods, microwave synthesis is more convenient to
synthesize and can be carried out in higher yields in short reaction
times under mild reaction conditions. In the present study, we re-
port the one pot synthesis, structural and spectral analysis of some
symmetrical curcumin analogues catalyzed by calcium oxide un-
der microwave irradiation.
H
H
+
+
H3C
CH3
R1
R1
CaO
R2
MW, 160W
60-120 sec
R5
O
3
O
R5
7
1
R4
R3
R4
R3
4
4
5
6
2
2
R1
R1
R2
R5
R2
R5
OH
3
O
7
1
R4
R3
R4
R3
5
6
R1
R1
1-16
R2
R2
Scheme 1. Synthesis of curcumin analogues.
(20 mg) was added. The reaction mixture was mixed properly with
the help of a glass rod (5 s) and then irradiated in a microwave
oven for 60–120 s at 160 W (monitored by TLC). The reaction mix-
ture was removed from the oven, cooled and 2% hydrochloric acid
(10 ml) was added and kept overnight. Then the reaction mixture
was shaken well with ethyl acetate (3 ꢁ 10 ml) and the catalyst
was removed by filtration. The filtrate was concentrated in vacuum
to afford the products 1–16 (Scheme 1).
Experimental
Spectroscopy
Microwave irradiation is performed by a conventional (unmod-
ified) domestic microwave oven equipped with a turntable (LG,
MG-395 WA, 230 V–50 Hz, 760 W). The infrared spectra are re-
corded on a Thermo Nicolet-Avatar-330 FT-IR spectrophotometer
using KBr (pellets) and noteworthy absorption values (cmꢀ1) are
obtained. 1H and 13C NMR spectra are recorded at 293 K on BRU-
KER AMX-400 Spectrometer operating with the frequencies of
400 MHz and 100 MHz respectively using CDCl3 as solvent. Sam-
ples are prepared by dissolving about 5 mg of sample in 0.5 mL
of CDCl3. All the chemical shift values are referenced to TMS.
UV–Vis measurements were performed using Shimadzu (UV-
1650) UV–Vis spectrophotometer at 20 °C in the 200–800 nm spec-
tral range employing a 1 cm quartz cell and 1 ꢁ 10ꢀ5 M methanolic
curcumin solution is used for acquisition. The mass spectra are re-
corded on a Varian Saturn 2200 MS spectrometer.
Results and discussion
The curcumin analogues (1–16) are synthesized in excellent
yields by the reaction of acetylacetone with appropriate aldehydes
catalyzed by activated calcium oxide under microwave irradiation
within 60–120 s. The reaction time, the yields and the melting
points of the synthesized products are given in Table 1. The struc-
tures of the all synthesized compounds (1–16) are confirmed by
UV absorption studies, FT-IR, 1H NMR, 13C NMR spectral studies
and elemental analysis.
In order to determine the structures of the synthesized com-
pounds, compound 1 is taken as the representative compound.
Structure of compound 1 is shown in Fig. 1.
Computational details
All the theoretical calculations are performed with ArgusLab
package. The geometry of all the involved structures is fully opti-
mized with AM1 calculation. The ESP-mapped electron density
surface maps of the optimized geometry structures of the curcu-
min and its analogues (except fluorine substituted compounds)
1–8, 10, 11 and the HOMO–LUMO orbital density diagram calcula-
tion are done using the same package.
Absorption studies
The absorption spectra of representative compound (1E,4Z,6E)-
5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-tri-
en-3-one (curcumin) shows absorption band around 420 nm in
methanol and the remaining curcumin analogues shows broad
and structureless bands. The absorption peaks of the compounds
2–16 are blue-shifted with respect to the absorption band of curcu-
min. The rather high oscillator strength is consistent with the
experimentally observed strong absorption spectrum of the keto-
enolic form [11]. The experimentally observed data of all these
synthesized compounds are listed in Table 2.
Experimental procedure for the synthesis of symmetrical curcumin
analogues
To a mixture of appropriate benzaldehyde (0.002 mol) and acet-
yl acetone (0.001 mol) in a 50 ml borosil beaker, calcium oxide
Elavarasan, S.
