Expedious synthesis for α, β-unsaturated coumarin derivatives using boran chelates: A novel class of potential antibacterial and antioxidant agents

Article abstract of DOI:10.1016/j.crci.2009.10.001

A new family of coumarin derivatives (4a-i) containing a chalcone moiety was synthesized by condensation of 3-acetyl-4-difluoro boryloxycoumarin (2) with aryl and heteroaryl aldehydes with piperidine in chloroform. Resulting compounds were characterized by IR, ¹³C, ¹H NMR and UV visible spectroscopy. Compound 3-((2E)-3-(3,4,5-Trimethoxy-phenyl)prop-2-enoyl)- 2(H)-chromen-2-one (4g) was characterized by single crystal X-ray diffraction. The antioxidant and antibacterial activities of the obtained compounds 4a-i was evaluated. The biological activity found for these compounds is discussed against their structural features, physical and chemical properties.

Full text of DOI:10.1016/j.crci.2009.10.001

C. R. Chimie 13 (2010) 1261–1268
Contents lists available at ScienceDirect
Comptes Rendus Chimie
www.sciencedirect.com
´
Full paper/Memoire
Expedious synthesis for
a, b-unsaturated coumarin derivatives
using boran chelates: A novel class of potential antibacterial and
antioxidant agents
a
b
c
Naceur Hamdi a, , Feten Bouabdallah , Antonio Romerosa , Rached Benhassen
*
a Department of Chemistry, Borj Cedria Higher Institute of Sciences and Technology of Environment, Ecopark of Borj Cedria Touristic, Touristic road of Soliman,
Hammam-Lif, BP 95, 2050 Tunis, Tunisia
b
´
´
´
´
Area de Quı´mica Inorganica, Universidad de Almerıa, 04120, Almerıa, Spain
c Unite´ chimie des mate´riaux, ISSBAT, universite´ Tunis El Manar, 9, avenue Dr. Zoheir Safi, 1006 Tunis, Tunisia
A R T I C L E I N F O
A B S T R A C T
new family of coumarin derivatives (4a–i) containing
Article history:
A
a chalcone moiety was
Received 24 September 2009
Accepted after revision 2 October 2009
Available online 1 February 2010
synthesized by condensation of 3-acetyl-4-difluoro boryloxycoumarin (2) with aryl and
heteroaryl aldehydes with piperidine in chloroform. Resulting compounds were
characterized by IR, 13C, 1H NMR and UV visible spectroscopy. Compound 3-((2E)-3-
(3,4,5-Trimethoxy-phenyl)prop-2-enoyl)-2(H)-chromen-2-one (4g) was characterized by
single crystal X-ray diffraction. The antioxidant and antibacterial activities of the obtained
compounds 4a-i was evaluated. The biological activity found for these compounds is
discussed against their structural features, physical and chemical properties.
Keywords:
Coumarin derivatives
Boron compounds
Chalcone
ß 2009 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Electronic absorption spectra
1. Introduction
derivatives have been used as inhibitors of lipoxygenase
(LOX) and cyclooxygenase (COX) pathways of arachidonic
Coumarins are compounds that display a special role in
nature. Pharmacologically, coumarins and their derivatives
are included in the family of the flavonoids and exhibit a
variety of interesting biological and pharmacological
activity. Therefore, coumarins and their derivatives have
raised considerable interest because of their potential
beneficial effects on human health [1,2]. They have been
reported to possess: anti-HIV [3–6], anticoagulant [7],
antibacterial [8,9], anticancer [10], anthelminthic [11],
anti-inflammatory [12–14] and antioxidant activities
[15–17]. As a result, coumarins and derivatives have been
the subject of extensive investigations.
acid metabolism [20]. One of the most well studied
coumarin-based anti-inflammatory drugs is cloricromene
(8-monochloro-3-b-diethylaminoethyl-4-methyl-7-eth-
oxy-carbonylmethoxy coumarin), and several synthetic
analogues of this compound have been recently reported
and tested for their anti-inflammatory and antioxidant
activities [21]. In addition, many coumarin derivatives have
shown special ability to scavenge Reactive Oxygen Species
(ROS) and in processes involving free radical injury [22,23].
In addition, the 4-hydroxycoumarin moiety, which widely
spreadsamongcoumarin, isthemoleculartemplateusedfor
the synthesis of a variety of analogue derivatives which
exhibit important biological activity.
In the course of our continuous interest on the synthesis
of coumarin derivatives including 4- hydroxyl coumarin
with antibacterial and antioxidant activities [24,25], we
have extended our research to the synthesis and biological
evaluation of new coumarinyl chalcones using 3-acetyl-4-
difluoro boryloxycoumarin coumarin (2) via an easy,
efficient and quit method.
The coumarin nucleus incorporates the styryl carbonyl
moiety into a rigid framework. It has been reported that
styryl carbonyl derivatives possess appreciable anti-inflam-
matory activity [18,19]. Moreover, coumarin and related
* Corresponding author.
E-mail address: naceur.hamdi@isste.rnu.tn (N. Hamdi).
1631-0748/$ – see front matter ß 2009 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2009.10.001

1262
N. Hamdi et al. / C. R. Chimie 13 (2010) 1261–1268
2. Results and discussion
the reaction was much longer, from 24 to 36 h at room
temperature [30–32]. Reaction of 3-acetyl-4-difluorobor-
yloxycoumarin (2) with aryl or heteroaryl aldehydes likely
takes place according to the probable rearrangement of 40
to give 4.
The formation of the new boronate coumarinic
chalcone probably takes place at the first stage, and the
deciding role in such a reaction path is played by the boron
atom coordinated with the nitrogen atom of piperidine
rearrangement of the complex 40, which leads to the
coumarin derivative 4. It should be noted that this reaction
of condensation is accompanied by elimination of the
difluorobopiperidine.
All the resulting products were isolated in solid state,
their purity was checked by thin layer chromatography
(eluctant: hexane/ethyl acetate, 1/1. v/v) and characterized
by NMR and IR spectroscopy. Reactions and obtained
products are displayed in Scheme 2 and Table 1.
The IR spectra of compounds 4a–i showed characteris-
The acetylation of 4-hydroxycoumarin to give 3-acetyl-
4-hydroxycoumarin (1) was carried out by the method of
Dholakia et al. [26] by using glacial acetic acid in the
presence of POCl3. The quick reaction led to the desired
product without obtaining any product from the intramo-
lecular condensation of 4-hydroxycoumarin [27]. We have
observed previously [28] that the reaction between
hydroxyacetylcoumarin and boron compounds substan-
tially increases the acidity of Ha atoms. For instance,
reactions of 3-acetyl-4-difluoro boryloxycoumarin (2)
with triethyl orthoformate, Fischer aldehyde and DMF
produces symmetrical and unsymmetrical polymethine
dyes in high yields [29] which are identified by their
intense absorption in the visible region and fluorescence
properties. Here we describe the condensation process of
compound 2 with aromatic aldehydes, which affords the
-unsaturated ketones from the coumarin series.
Heating 3-acetyl-4-hydroxycoumarin in a mixture of
a,
b
—
—
tic absorptions for OH, (ketone) C O and (lactone) (C O)
—
—
toluene and boron trifluoride etherate gave rise to the
boron product 2 with good yield (Scheme 1).
stretching in the region 3500–3300 cmꢀ1
,
1670–
1710 cmꢀ1 and 1720–1750 cmꢀ1, respectively. The spec-
troscopic characterization of compound 4g is presented as
an example. The 1H NMR spectra of 4g shows the aromatic
proton as a multiplet between 7.41 and 8.21 ppm, the
singlets at 3.74 and 3.85 ppm were assigned as methoxylic
protons. The 13C NMR spectrum of 4g in DMSO is
constituted by two downfield signals at 162.42 ppm
(Ketone CO) and 157.41 ppm (lactone CO) as well as one
upfield signal at 55.48 ppm (OCH3). The DEPT spectrum
showed that the HC carbons of the coumarinic ring appear
Compound 2 was characterized by 1H NMR, 13C NMR,
and IR spectroscopy. The 1H NMR spectra of 2 display the
signal for the protons of the methyl group of the acetyl
fragment shifted to downfield than those found for the
starting compound 3-acetyl-4-hydroxycoumarin. The car-
bonyl IR intense stretching band of 3-acetyl-4-hydroxy-
coumarin observed at 1740 cmꢀ1 remains virtually
unchanged for compound 2 while the carbonyl band for
acetyl group arises at 1560 cmꢀ1 instead at 1600 cmꢀ1 as is
observed in starting compound and additionally this band
is less intense for 2 than for 3-acetyl-4-hydroxycoumarin.
That fact could be justified by the donor acceptor
interaction with boron atom of the acetyl group. In the
1000–1100 cmꢀ1 interval, there are two intense absorp-
tion bands (1045 and 1070 cmꢀ1) which can be assigned to
C-O-B stretching vibrations.
at
d 134.5, 131.3, 125.6 and 124.11 ppm. The low field
region of the spectra of compounds 4g shows the signals
for the aromatic protons between 7.4 and 8.1 ppm and
doublet signals for olefin protons in the same region with
3JHH = 13.5 Hz. These coupling constants are in agreement
with a disposition for the olefin protons trans to each other.
In order to confirm the proposed composition for 4g, its
crystals structure was determined by single crystal X-ray
diffraction analysis (Fig. 1).
The X ray crystal structure confirmed the propose
composition for 4g. A more accurate description of the
structure was presented in [33] but it is important to point
out that along the connection between the coumarin
The coumarinic chalcones 4a-i was synthesized in one
step by a new procedure: refluxing 3-acetyl-4-difluor-
oboryloxycoumarin (2) with aryl and heteroaryl aldehydes
in the presence of piperidine in chloroform. Using this
reaction conditions, the reaction time is c.a. 1–1.5 h. In
previously used methods, the time needed for completing
Scheme 1. Synthesis of 3-acetyl-4-difluoro boryloxycoumarine.

N. Hamdi et al. / C. R. Chimie 13 (2010) 1261–1268
1263
Scheme 2. Formation of the coumarinic chalcones 4 by the reaction of 3-acetyl-4-difluoroboryloxycoumarin (2) with aryl and heteroaryl aldehydes.
moiety and phenyl ring (C13–C12–C11–C10) the double
spectrum of 4f, in which both chromophores are directly
condensed without any spacer between them, shows only
one band at 525 nm with a shoulder at short wavelengths.
For all the coumarinic chalcones the magnitude of the
˚
bond is located on C11–C12 (C11—C12 = 1.325 (5) A; C10—
˚
˚
C11 = 1.467 (5) A; C12— C13 = 1.475 (4) A). Therefore, there
is a -bridge for the charge transfer from phenyl ring to
p
coumarin moiety. As well, it is interesting to stress that
intermolecular and intramolecular hydrogen bonds are
between C2–HꢁꢁꢁO3 and C19–HꢁꢁꢁO4 leading to a hydrogen
network among molecules (Fig. 2).
molar absorption coefficient is typical of
(Table 2).
p–p transitions
3. Antioxidant activities of compounds 4a–i
The electronic absorption spectra of compounds 4a–i
were obtained in chloroform and are displaying in Fig. 3.
The spectrum shows intense narrow bands with a high
extinction coefficient. Compounds absorb in the same
spectral region but the shape of their absorption spectra
differs with the nature of the tether. The spectra of 4b
display two bands at around 450 and 600 nm. The
The synthesized compounds 4a–i were tested for their
antioxidant and antibacterial activities. It is well known
that free radicals play an important role in the inflamma-
tory process [34]. Many non-steroidal anti-inflammatory
drugs have been reported to act either as inhibitors of free
radical production or as radical scavengers [35]. Conse-
Table 1
Table 2
Obtained products and aryl aldehydes substituent groups.
Spectral properties of the coumarinic chalcones 4a-i in chloroform.
e
molꢀ1 dm3 cmꢀ1
4a-i
Ar
Compounds 4a-i
lmax (nm)
a
b
c
d
e
f
C6H5
a
b
c
d
e
f
494
474
452
476
463
482
466
477
484
30,400
23,000
16,300
8530
pF- C6H4
pOCH3C6H4
pMe C6H4
pBr C6H4
14,815
23,200
14,500
28,500
7300
pNO2 C6H4
3,4,5 OCH3 C6H2
C10H7
g
h
i
g
h
i
pN(Me)2 C6H4

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N. Hamdi et al. / C. R. Chimie 13 (2010) 1261–1268
Fig. 1. Solid state structure of 3-((2E)-3-(3,4,5-Trimethoxy-phenyl)prop-2-enoyl)-2(H)-chromen-2-one (4g).
Fig. 3. Absorption spectra of the coumarins chalcones in chloroform
solution. These compounds were also characterized to determine their
UV–vis absorbance spectra, and molar absorption coefficients.
plethora of methods used for the evaluation of the
antioxidant activity, the 1, 1-diphenyl-2-picrylhydrazyl
(DPPH) test is very useful in the micromolar range
Fig. 2. Unit cell view of the crystal down c-axis showing intermolecular
demanding minutes to hours for a, b-unsaturated ketones
and intermolecular hydrogen bonds (dashed lines).
of the coumarinic series samples. Where the structure of
the electron donor is not known, this method can afford
data on the reduction potential of the sample, and hence
can be helpful in comparing the reduction potential of
unknown materials. The competition of the compounds
with DMSO for hydroxyl radicals has been used, whereas
antioxidant capability as well as lipid peroxidation
inhibitory activity was assayed by the inhibition of the
oxidizing enzyme LOX [36]. The interaction of the
quently, compounds with antioxidant properties could be
expected to offer protection in rheumatoid arthritis and
inflammation and to lead to potentially effective drugs. The
potential of the antioxidant activity is shown in Fig. 4 and
Table 3.
Results of a single assay can give only a suggestion on
the protective potential of tested compounds. Among the

N. Hamdi et al. / C. R. Chimie 13 (2010) 1261–1268
1265
Table 4
Antimicrobial activity spectrum of compounds 4a–i.
Organism indicator
Inhibition
Compounds
zone (mm)
Staphylococcus aureus
30
4a
(CIP 7625)
28
4b
25
4c
32
4d
35
4e
26
4f
24
4g
31
4h
24–28
Gentamycin
Fig. 4. The DPPH radical scavenging capacity of the obtained coumarinic
derivatives 4a-i.
Staphylococcus aureusa
25
27
26
31
34
27
25
32
39
24
4a
4b
4c
Table 3
4d
The EC50 values exhibited by coumarinic chal-
cones 4 are summarized in the following table.
4e
4f
4g
Compounds 4a-i
EC50 (mM)
4h
4a
4b
4c
4d
4e
4f
2.39
2.34
3.03
2.24
2.10
2.16
2.42
2.29
2.18
4i
Gentamycin
Escherichia coli ATCC 25922
28
4a
26
4b
34
4c
31
4d
4g
4h
4i
30
4e
27
4f
25
4g
32
4h
22–26
Gentamycin
examined compounds with the stable free radical DPPH
was studied (Table 2). This interaction indicates their
radical scavenging ability in an iron-free system using a
stable free radical which can accept an electron or
hydrogen atom.
The comparative study among the resulting test results
for compounds shows that compounds 4a and 4d are
potent antioxidant compounds while coumarinic chalcone
Klebsiella pneumonia
23
4a
CIP 104727
25
30
29
27
28
26
31
32
21
4b
4c
4d
4e
4f
4g
4h
4i
4c is inactive even at
a concentration of 3.77 mM.
Gentamycin
Compounds 4e and 4i proved to be the most active
compounds in this study. Comparing the activity of
compounds 4f–h it was concluded that there is not a
substantial difference when we change the nature of the
substituent Ar.
Pseudomonas aeruginosa
27
4a
27853 (CIP 76110)
25
4b
33
4c
32
4d
30
4e
26
4f
4. Antibacterial activities of compounds 4a–i
27
4g
30
4h
New antimicrobials are needed because of the emer-
gence of organisms that are resistant to available
antimicrobials.
The new coumarinic fluorine chalcones derivatives 4a–i
were also screened in vitro for their antimicrobial activity
against a variety of bacterial strains.
The results of these studies are summarized in Table 4.
It could be observed that all the tested compounds were
active toward E. Coli,
31
4i
15,5–22,5
Gentamycin
The residual antibacterial activity in the compounds was tested by disc
diffusion assay against the indicator strain in LB medium at 28 8C. ATCC:
American Type Culture Collection; USA; CIP: collection de l’Institut Pasteur,
Paris, France; LM: laboratoire de microbiologie, Centre national de greffe de
moelle osseuse, Tunis, Tunisia.
a
Methicillin-resistant clinical isolates.
The antibacterial data of the above compounds having
pBrC6H4 group have increased antibacterial activity while
4h–i are found to be more biologically active than 4b–c
[37].
The antibacterial test results depicted in Table 4 shows
that the new compounds 4a–i show interesting antibacte-
rial activities but moderate. Nevertheless, the obtained
results clearly demonstrate that this kind of compounds
could be an effective antibacterial agent and the activity is
depending on the chemical composition of the coumarine
derivative.

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N. Hamdi et al. / C. R. Chimie 13 (2010) 1261–1268
5. Conclusion
In the present study, as
and aromatic aldehydes were purchased from Fluka, DMF
was purified, dried and distillated over CaH2 prior to use.
a
first step, we have
successfully developed a synthetic route for the prepara-
tion of novel coumarins derivatives. Their synthesis is
easy, quit and convenient with satisfactory yield. The
synthetic procedure is not sensitive to oxygen and water
and it is easy to operate at room temperature. The
flexibility of this methodology should provide access to
many various coumarins chalcones. All these compounds
are observed to exhibit excellent absorbance properties.
The DPPH method has been widely applied for estimating
antioxidant activity in recent years but its applications
should be carried out bearing in mind the basis of this
method. Nevertheless, it can be concluded that the
antioxidant activity of the coumarine-synthesized deri-
vatives could be related to their structure. Antioxidant
activities of these compounds against the stable free
radical DPPH show that these species are compounds that
could help to increase the overall antioxidant capacity of
an organism. Therefore, the design of this type of dual
acting molecules should be further explored on the base of
the structural features of these compounds. The adducts
4e and 4i present the highest activity from all the tested
compounds.
6.3. 3-Acetyl-4-hydroxycoumarin
To a solution of 4-hydroxy-2H-chromen-2-one (3 g,
1.86 mmol) in acetic acid (16 ml) was added phosphorus
oxychloride (5.6 ml). The mixture was heated at reflux for
30 min. After cooling, the precipitate was collected and
recrystallized from ethanol to give 3-acetyl-4-hydroxy-2H-
chromen-2-one as white needles. Yield 2.7 g (90%);
mp = 135 8C. IR spectrum,
n
cmꢀ1: 3185 (OH); 1705 (CO);
ppm:
1700 (O–CO lactone). 1H NMR spectrum (CDCl3).
d
2.72 (3H, s, CH3); 7.98 (1H, s, H-5); 7.95 (1H, dd, 3J7.8 = 8.35,
4J6.8 = 1.2, H-8); 7.1–7.4 (2H, m, H-6 + H-7); 17.69 (1H, s, OH).
13C NMR spectrum (CDCl3),
d ppm: 29.9 (CH3); 178.5 (CO);
159.8 (C-4); 154.6 (C-2); 101.26 (C-3); 115.0–136.0 (Carom).
Massspectrum, m/z(I, %):204[M]+ (100);189(74);161(43).
6.4. 3-acetyl-4-difluoro boryloxycoumarin coumarin
To
a solution of 3-acetyl-4-hydroxycoumarin (3 g,
1.86 mmol) in toluene (16 ml) was added BF2OEt2
(5.6 ml). The mixture was heated at reflux for 60 min.
After cooling, the precipitate was collected and recrys-
tallized from ethanol to give 3-acetyl-4-difluoro borylox-
ycoumarin coumarin as white needles. Yield 2.7 g (90%);
6. Experimental section
mp = 135 8C. IR spectrum,
lactone). 1H NMR spectrum (CDCl3).
CH3); 7.02–7.27 (m, Harom). 13C{1H} NMR spectrum
(CDCl3), ppm: 26.7 (CH3); 198.7 (CO); 170.0 (C-4);
n
cmꢀ1: 1705 (CO); 1700 (O–CO
ppm: 2.3 (3H, s,
6.1. General procedures
d
Flash chromatography was carried out on 0.04–
0.063 mm (Merck) silica gel, thin layer chromatography
was carried out on aluminium backed silica plates by
Merck and plates were revealed using a UV 254 light. 1H
NMR (300 MHz) and 13C NMR (75 MHz) spectra were
recorded on a Varian VXR 300 instrument at 293 8K in
CDCl3 and DMSO-d6. Spectra were internally referenced to
TMS. Peaks are reported in ppm downfield of TMS.
Multiplicities are reported as singlet (s), doublet (d),
triplet (t), quartet (q). Characterization was made some
time by using DEPT experiment. The IR-spectra were
recorded on a Philips Analytical PU 9800 spectrometer. The
melting points of compounds were determined in open
glass capillaries in a paraffin bath and are uncorrected. The
absorption spectra were measured on a Beckmann K25
spectrophotometer.Absorbance spectra for all compounds
were collected at room temperature with a Hewlett-
Packard (Palo Alto, CA) model 8453 diode array UV–vis
spectrophotometer. Absorbance measurements were tak-
en using Eppendorf (Hamburg, Germany) UVette cuvettes
(220–1600 nm). Elemental microanalysis was obtained by
the microanalytical laboratory services, university of Cadiz
in Spain.
d
159.5 (C-2); 102.3 (C-3); 121.5–126.8 (Carom).
6.5. General procedure for the preparation of the coumarinic
chalcones 4a–i
3-acetyl-4-difluoro
boryloxycoumarin
coumarin
(0.031 mol) and the substituted aromatic aldehyde
(0.03 mol) were dissolved in 30 mL of chloroform. A
catalytic amount of piperidine (0.02 mol) was added and
the reaction mixture was refluxed for 1.5 h. The chloroform
was removed under vacuum and the residue was washed
with methanol.
6.6. 3-((2E)-3-(phenyl)prop-2-enoyl)-2(H)-chromen-2-one
(4a)
Solid (yield 79%); mp = 145 8C, there is
a lactone
carbonyl in IR spectrum,
—
(ppm): 7.2–8.3 (m, 11H, Ar-H + Hethyl). 13C{1H} NMR
(ppm): 178.6 (CO); 179.1 (C4); 155.1 (C2); 179.1 (C4),
179.1 (C4), 101.8 (C3), 126.2–136.5 (Carom); 129.7
cmꢀ1: 1622 (C O), 1577
—
n
—
(C C), 1028 (s) (sym) (C-O-C), 1727 (O-CO). 1H NMR:
d
—
´
´
´
In the experiment part, the 13C {1H} NMR should be
replaced by 13C NMR. The 1H-NMR have been checked for
the multiplicities for H-atoms.
(Cethyl1), 147.8 (Cethyl2). C18H1204 calc. C 73.97, H
4.10, O 21.92; found. C 73.90, H 4.10, O 21.80.
6.7. 3-((2E)-3-(4-fluorophenyl)prop-2-enoyl)-2(H)-
chromen-2-one (4b)
6.2. Materials
DPPH was obtained from Sigma. All other chemicals
were of analytical grade purity. The 4-hydroxycoumarin
Solid (yield 80%); mp = 178 8C. IR spectrum, n :
cmꢀ1
1
—
—
1622 (C O), 1577 (C C), 1028 (s) (sym) (C-O-C); H NMR:
—
—

N. Hamdi et al. / C. R. Chimie 13 (2010) 1261–1268
1267
´
d
(ppm): 7.2–8.2 (m, 10H, Ar-H + Hethyl). 13C{1H} NMR
6.13. 3-[(2E)-3-(naphthyl) prop-2-enoyl]-2(H)-chromen-2-
one (4h)
(ppm): 160.5 (CO); 179.1 (C4); 155.1 (C2); 179.1 (C4),
179.1 (C4), 101.8 (C3), 115.6–136.5 (Carom); 129.7
(Cethyl1), 147.8 (Cethyl2). C18H1104 F calc. C 69.67, H
Solid (yield 80%); mp = 185 8C. IR spectrum,
n
cmꢀ1
1718 (s) (C O), 1578 (C C), 1019 (s) (sym) (C-O-C); 1H
:
´
´
—
—
3.54, O 20.64; found. C 69.70, H 3.60, O 20.70.
—
—
NMR:
NMR (ppm): 180.1 (CO); 195.0 (C4); 155.1 (C2); 117.4 (C3),
(ppm): 7.2–9.1 (m, 13H, Ar-H + Hethyl). 13C{1H}
´
d
6.8. 3-((2E)-3-(4-methoxyphenyl)prop-2-enoyl)-2(H)-
chromen-2-one (4c)
´
´
123.5–143.9 (Carom); 129.3 (Cethyl1), 149.5 (Cethyl2).
C
22H1404 calc. C 77.20, H 4.10, O 18.71; found. C 77.10, H
Solid (yield 70%); mp = 135 8C. IR spectrum,
n
cmꢀ1
:
4.10, O 18.70.
1
—
—
1622 (C O), 1577 (C C), 1028 (s) (sym) (C-O-C). H NMR:
—
—
´
d
(ppm): 3.74 (s,OCH3), 7.1–8.3 (m, 10H, Ar-H + Hethyl).
6.14. 3-((2E)-3-(4-Dimethylamino-phenyl) prop-2-enoyl)-
2(H)-chromen-2-one (4i)
13C{1H} NMR (ppm): 181.1 (CO); 190.9 (C4); 162.4 (C2);
´
100.3 (C3); 113.6–157.6 (Carom); 128.3 (Cethyl1), 154.0
´
(Cethyl2). C19H1405 calc. C 70.80, H 4.34, O 24.84; found. C
Solid (yield 85%); mp = 192 8C. IR spectrum, n :
cmꢀ1
1
— —
1712 (s) (C O), 1550 (C C), 1028 (sym) (C-O-C); H NMR:
— —
70.70, H 4.40, O 24.80.
´
(ppm): 3.2 (s, 6H, 2CH3), 6.8–8.4 (m, 10H, Ar-H + Hethyl).
d
6.9. 3-((2E)-3-(p-tolyl) prop-2-enoyl)-2(H)-chromen-2-one
(4d)
13C{1H} NMR (ppm): 40.5 (CH3), 180.1 (CO); 190.1 (C4);
153.3 (C2); 112.2 (C3), 116.1–135.8 (Carom); 132.6
´
´
(Cethyl1), 149.9 (Cethyl2). C20H1704 N calc. C 71.64, H
Solid (yield 75%); mp = 140 8C. IR spectrum,
n :
cmꢀ1
5.1, O 19.10, N 4.17; found. C 71.60, H 5.10, O 19.30, N 4.20.
1
—
—
1625 (C O), 1580 (C C), 1030 (s) (sym) (C-O-C). H NMR:
—
—
´
d
(ppm) 2.84 (s, 3H, CH3); (7.28 (d, 1H, Hethy1), 7.60 (d, 1H,
´
7. The experimental procedure for antioxidant
evaluation
Hethy2), 7.2–8.2 (m, 8H, Ar-H). 13C{1H} NMR (ppm): 30.0
(OCH3); 178.4 (CO); 154.6 (C4); 135.6 (C2); 101.3–135.9
(Carom). C19H1404 calc. C 74.50, H 4.57, O 20.91; found. C
74.40, H 4.60, O 20.90.
The DPPH radical’s scavenging capacity of the obtained
coumarinic derivatives was measured from the bleaching
of purple colored ethanol solution of DPPH. The method
described by Hatano et al. [32] was used. Half a millilitre of
each sample concentration was mixed with an equal
volume of DPPH ethanolic solution. After incubation for
30 minutes in darkness at 25 8C, absorbance was read at
520 nm wavelength. A mixture of 0.5 ml of DPPH solution
and 0.5 ml of ethanol was taken as a blank (absorbance is
equal to zero). Inhibitory concentration (IC50) values
denoting the concentration (microgram of natural sub-
stance per milliliter of ethanol) required to scavenge 50% of
DPPH radicals were calculated. All measurements were
performed in triplicate. Results were expressed in inhibi-
tion percentage versus sample concentrations (mg/ml) at
30 mins.
6.10. 3-[(2E)-3-(4-bromophenyl)prop-2-enoyl]-2(H)-
chromen-2-one (4e)
Solid (yield 85%); mp = 182 8C. IR spectrum,
n :
cmꢀ1
1
—
—
1622 (C O), 1577 (C C), 1028 (s) (sym) (C-O-C). H NMR:
—
—
(ppm): 7.2–8.0 (m, 10H, Ar-H + Hethyl). 13C{1H} NMR
(ppm): 178.7 (CO); 181.5 (C4); 160.2 (C2); 101.3 (C3),
´
d
´
´
122.6–154.7 (Carom); 130.0 (Cethyl1), 154.3 (Cethyl2).
18H1104Br calc. C 58.22, H 2.96, O 17.25; found. C 58.30, H
C
2.90, O 17.30.
6.11. 3-((2E)-3-(4-Nitro-phenyl) prop-2-enoyl)-2(H)-
chromen-2-one (4f)
Solid(yield 85%); mp = 182 8C. IR spectrum,
n :
cmꢀ1
1
—
—
1622 (C O), 1577 (C C), 1028 (s) (sym) (C-O-C); H NMR:
8. The experimental procedure for the antibacterial
evaluation
—
—
´
d
(ppm): 6.8–8.3 (m, 10H, Ar-H + Hethyl). 13C{1H} NMR
(ppm): 171.3 (CO); 180.5 (C4); 163.3 (C2); 100.9 (C3),
´
´
122.6–152.5 (Carom); 129.6 (Cethyl1), 151.7 (Cethyl2).
C
64.10, H 3.30, O 24.50, N 4.10.
Bacteria used as indicator strains for the determination
of the antimicrobial activity spectrum were grown in
appropriate culture conditions, as indicated in Table 4.
Stock cultures were maintained at ꢀ80 8C in broth
supplemented with 25% (v/v) glycerol.
The standard drug used for comparison is gentamycin
(MIC + 15 ug/ml).
The tested compounds were dissolved in MeOH to
obtain 0.5 mg/mL solution and was tested for antibacterial
activity by disc diffusion assay as previously described
18H1106 N calc. C 64.1, H 3.26, O 24.48, N 4.15; found. C
6.12. 3-((2E)-3-(3,4,5-Trimethoxy-phenyl)prop-2-enoyl)-
2(H)-chromen-2-one (4g)
Solid (yield 83%); mp = 193 8C. IR spectrum,
n
cmꢀ1
1716 (s) (C O), 1577 (C C), 1018 (s) (sym) (C-O-C); 1H
:
—
—
—
—
NMR:
d (ppm): 3.74 (s, 3H, OCH3), 3.85 (s, 6H, OCH3), 7.4–
8.1 (m, 8H, Ar-H). 13C{1H} NMR (ppm): 55.9 (OCH3), 60.1
(OCH3), 191.2 (CO); 180.7 (C4); 159.5 (C2); 100.6 (C3),
[38]. An aliquot (10 ml) of was applied onto discs (6 mm
diameter) on agar plates previously inoculated with the
indicator strain suspension. Plates were incubated for 24 h
at 28 8C, the optimal temperature of the tested micro-
organisms, and diameter of inhibition zone was evaluated.
´
´
126.2–136.5 (Carom); 129.6 (Cethyl1), 153.3 (Cethyl2).
21H1807 calc. C 65.96, H 4.71, O 29.31; found. C 65.90, H
4.80, O 29.30.
C

1268
N. Hamdi et al. / C. R. Chimie 13 (2010) 1261–1268
[16] H.G. Raj, V.S. Parmar, S.C. Jain, S. Goel, Pooman, S. Himanshu, A.
Acknowledgments
Malhotra, C.E. Singh, J. Olsen, Wengel, Bioorg. Med. Chem. 6 (1998)
833.
This work was carried out with financial aid of both
Tunisian Ministry of Higher Education and Scientific
Research and Technology and the Spanish Agency of
International Cooperation through projects (A/9549/07
and A/8302/07).
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