International Journal of Organic Chemistry, 2011, 1, 87-96
doi:10.4236/ijoc.2011.13014 Published Online September 2011 (http://www.SciRP.org/journal/ijoc)
Synthesis, Spectroscopy and Electrochemis try of New
3-(5-Aryl-4,5-Dihydro-1H-Pyrazol-3-yl)-4-Hydroxy-2H-
Chromene-2-One 4, 5 as a Novel Class of Potential Anti-
bacterial and Antioxidant Derivatives
Abdullah Sulaiman Al-Ayed
College of Science and Arts at Ar-Rass, Qassim University, Kingdom of Saudi Arabia
Received June 24, 2011; revised August 1, 2011; accepted August 10, 2011
Abstract
3-((2E)-3(aryl)prop-2-enoyl)-2H-chromen-2-one 3 was synthesized from 4-hydroxy coumarin by refluxing
3-acetyl-4-hydroxy coumarin with aromatic aldehydes in chloroform in the presence of a catalytic amount of
piperidine. 3 was converted to pyrazoles 4, 5 by treatment with hydrazine and phenylhydrazine in toluene,
respectively. The structures of the new compounds were confirmed by elemental analysis, IR, and multinu-
clear/multidimensional NMR spectroscopy (1H, 13C-NMR, NOESY, HMBC) which allowed us to assign the
complete network of proton and carbon atoms. All the compounds exhibited one quasireversible redox proc-
ess. All the newly synthesized compounds were screened for their antibacterial and antioxidant activities.
Antimicrobial studies revealed that 3-(5-(2,5-dimethylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-4-
hydroxy-2H-chromene-2-one 5c showed significant antibacterial activity against Escherichia coli and Pseu-
domonas Aeruginosa 27853. Furthermore, 3-(5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-
2-ones 4, 5 showed antioxidant activities of different extents with respect to individual compounds as well as
to the antioxidant methods. The 3-(5-(phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-ones
4a was found to be the most active antioxidant in the series and more active than trolox which makes the in-
vestigated complexes a new promising class of antibacterial compounds.
Keywords: 4-Hydroxycoumarin, Pyrazole, Antibacterial Activity, Antioxydant Activity
1. Introduction
Chalcones are important precursors of flavonoids and
isoflavonoids [1]. A large number of chalcones have
been prepared by Claisen-Schmidt condensation of al-
dehydes with methyl ketones under basic conditions [2].
These compounds have shown in vitro antimalarial ac-
tivity against chloroquine-sensitive and chloroquine-re-
sistant strains of Plasmodium falciparum [3]. Recently
authors have reported the synthesis of chalcones under
acidic conditions using perchloric acid and acetic acid [4].
The activity of a variety of chalcones as potent tyrosinase
inhibitors and antioxidants has been also reported which
are, thus, used as new depigmentation agents [5]. Nitro-
gen heterocycles containing chalcone moiety have been
reported as active compounds against herpes simplex
virus-1 (HSV-1) and human immunodeficiency virus 1
(HIV-1) [6,7]. This class of compounds also exhibits
cytotoxic activity towards leukemia cell lines [8,9].
Various other chalcones exhibit insecticidal, antichino-
viral, and antipicorniviral properties [10].
On the other hand, coumarins and structurally related
compounds have been shown to inhibit replication of
HIV and thus exhibit a therapeutic potential [11]. A large
number of structurally novel coumarin derivatives have
been reported to show substantial cytotoxic and anti-HIV
activity both in vitro and in vivo [12,13]. A variety of
synthetic coumarins have unique action mechanisms
referring to the different stages of HIV replication [14].
Thus, coumarins are important lead compounds for the
development of antiviral and/or virucidal drugs against
HIV [15-17].
In view of the variety of pharmacological properties
exhibited by chalcones, we were prompted to undertake

A. S. AL-AYED
88
the synthesis of new compounds of this class and to
study their conversion to other heterocycles which may
show different or better physiological activities. We re-
port herein the synthesis of new chalcone derivatives and
their conversion to pyrazoles using nitrogen bases. In this
regard it is worth stressing that also pyrazoles have been
reported to show anti-inflammatory [18,19], cytotoxic
[20], insecticidal [21], herbicidal [22], and fungicidal
[23,24] activity.
1.1. Chemistry
Due to the exceptional reactivity of the acetyl group in
3-acetylchromone as well as the versatile biological ac-
tivities of coumarin derivatives, the chalcone 3 was syn-
thesized from 4-hydroxycoumarin (1) under mild basic
conditions.
Compound 2 was prepared by reaction of 4-hydroxy-
coumarine with POCl3 in chloroform in the presence of
acetic acid, The resulting compound 2 was then reacted
with arylaldehydes to give the (E) the coumarinic chal-
cones 3, which precipitated out from the hot MeOH solu-
tion after mixing 2 with the corresponding ArCHO
Scheme 1.
3-((2E)-3(aryl) prop-2-enoyl)-2H-chromen-2-one com-
pounds 3a-3e were identified from analysis of their spec-
troscopic data. The infrared (IR) spectrum of compound
3d showed the coumarin carbonyl groups at 1768 cm–1,
in addition to a broad band for the C=C group at 1595
cm-1. The 1H NMR spectrum showed trans olefinic pro-
tons Ha and Hb as ortho-coupled doublets at 8.25 (J =
15.6 Hz) and 6.92 (J = 15.9 Hz), respectively. The re-
maining aromatic protons of the aromatic aldehydes and
the four protons of the coumarin moiety appeared as a
multiplet in the region δ 7.25 - 8.08.
The 13C{1H} NMR spectrum of 3d in DMSO-d6
showed two downfield signals at ä 147.4ppm (C4) and ä
162.4 ppm (lactone C = O) as well as an up field signal
to at ä 55.4 ppm (OCH3). The condensation of hydrazi-
nes with α,β-unsaturated carbonyl compounds usually
gives pyrazolines [25] activities. Thus, when compound
3 was treated with nitrogen bases such as hydrazine and
phenylhydrazine, the pyrazolines 4 and 5 were obtained,
respectively. (Scheme 2)
O
OH
O O
OH
O
O
O
OH
O
O
iii
R
i: POCl
3
, ACOH, ii: CHCl
3
, piperidine, Arylaldehyde
123
Compounds 3 R
3a H
3b F
3c 2,5 CH3
3d OCH3
3e NO2
Scheme 1. synthesis of chalcones 3.
O
OH
O
O
3
NH
2
NH
2
O
OH
O
NNH
4
O
OH
O
NN
5
R
RR
PhNHNH
2
toluene t oluene
Yield (%)
Compounds 3 R Compounds 4
R’= H
Compounds 5
R’=ph 4 5
3a H 4a 5a 65 70
3b F 4b 5b 75 72
3c 2,5 CH3 4c 5c 80 78
3d OCH3 4d 5d 85 75
3e NO2 4 e 5e 80 75
Scheme 2. Synthesis of 3-(5-aryl-4, 5-dihydro-1h-pyr azol-3-yl)-4-hydroxy-2h-chromene-2-ones 4, 5.

A. S. AL-AYED 89
All the new 3-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-4-
hydroxy-2H-chromene-2-ones 4, 5 were characterized by
IR, 1H, 13C-NMR spectra as well as by NOESY and
HMBC 2D-NMR experiments to elucidate their struc-
tures and assign completely the structural network of
both protons and carbons. The spectral data were in ac-
cordance with the proposed structures (see experimental
section).
The IR spectrum of 4d showed broad band at 3207
cm–1 due to the presence of the NH group. A sharp and
strong absorption band at 1668 cm–1 indicated a carbonyl
group in the compound.
Since chromone carbonyl groups usually appear as
sharp absorption bands in the region 1620 - 1650 cm–1
[26], the band at 1684 cm–1 was assigned to coumarin
rather than the chromone carbonyl group.
In addition, the detection of a strong C=N stretching
band at 1608 cm−1 evidenced the formation of the pyra-
zole ring. The 1H NMR spectra of 4d displays a signal at
δ 4.12 ppm ascribable to the CH2 protons of the pyrazole
ring. A characteristic singlet proton signal at δ 4.81 ppm
was assigned to CH proton from the pyrazole fragment.
In addition, the aromatic protons (both coumarinic and
aromatic) are observed between δ 6.82 and δ 8.1ppm (see
experimental).
Full assignment of the 1H NMR spectra of 4d was de-
duced from the NOESY spectrum. An observed NOE
cross peak between H-1’ and aromatic protons confirms
that these two units are located on the same side of the
pyrazole ring.
The structure of 4d was finally elucidated through the
analysis of the 1H, 13C HMBC spectrum, which corre-
lates the protons at δ 4.78 ppm with C5' (δ 55.05 ppm)
and C2’ (δ 153.3 ppm). The aromatic protons correlate
with C5’ (δ 55, 05 ppm). (Table 1)
Table 1. Correlations between HMBC and NOESY for com-
pound 4d.
Proton
H-n
HMBC
H-n-C-j
NOESY
H-n-H-j
H-1’ 2, 2’, 5’ Harom
H-5’ 1’,7’
H-arom 5’
A mechanistic rationalization for this reaction is
straightforward and is provided in Scheme 3.
The first reaction step consists of a nucleophilic attack
of the final hydrazine nitrogen atom to the carbonyl
function followed by the elimination of water. The in-
termediate which forms may easily rearrange to afford
the corresponding pyrazoles 4, 5.
1.2. Results and Discussion
1.2.1. Electrochemistry
Electrochemical studies of 3-(5-aryl-4,5-dihydro-1H-
pyrazol-3-yl)-4-hydroxy-2H-chromene-2-one, 5, are of in-
terest due to the electron-deficient nature of the pyrazole
unit.
Hence, the electrochemical properties of compounds
5a-e, were determined by cyclic voltammetry in CH3CN
(1 × 10–3 M) solutions, using 0.1 M tetrabutylammonium
bromide (C4H12BrN) as the supporting electrolyte. Both
platinum and gold were used as working electrodes,
Ag/AgCl (0.1 M) as the reference electrode, and plati-
num as the counter electrode. Under these electrochemi-
cal conditions, 5 shows a quasi reversible behavior for
the first reduction process. This can be deduced from the
fact that the cathodic–anodic peak separations (Epc - Epa)
are ca. 100 mV. The ratio of the peak current intensity
for the cathodic and anodic processes is about 0.5 - 0.7.
O
OH
O
O
R
3
O
OH
O
NNR'
4,5
NH
2 NH R'
O
OH
O
OH
NH NHR'
-H
2
O
O
OH
O
NNHR'
(i) (ii)
RR
R
R': H, Ph
Scheme 3. Proposed mechanism for the synthesis of 4, 5.

A. S. AL-AYED
90
As expected, the reduction peak potential of the 3-(5-aryl-
4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-
2-one 5 are strongly influenced by the para substitutent
on the phenylene ring. Compared to the unsubstituted
compound 5, the presence of electron donor groups such
as the methoxy group shifts the reduction peak potential
of 5 to more negative values. The redox behavior of all
the new pyrazoles are summarized in Figure 1 All the
compounds exhibited one quasireversible redox processes.
For example, compounds 5d showed one quasirever-
sible reduction at –0.8 V and –1.15 V, respectively. We
assume that the curve at lower reduction potential may
be due to the more electron-deficient dications in the ring
system, and the curve at higher reduction potential may
be attributed to the redox behavior of the pyrazole unit.
1.2.2. Antiba cterial and Antioxi dant Studies
1.2.2.1. Free radical scavenging activity assay
The free radical scavenging activity of the new 3-(5-aryl-
4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-
2-one 4, 5 was tested by utilizing DPPH scavenging [34].
DPPH is a free radical and accepts one electron or one
hydrogen radical to become a stable diamagnetic mole-
cule [27]. The reduction capability of DPPH radical was
determined by the decrease in absorbance induced by
3-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-
chromene-2-one 4, 5. Briefly, 1.5 ml ethanolic solution
of the synthesized compounds (0.2 mM) was added to
1.5 ml (0.2 mM) solution of DPPH radical in ethanol
(final concentration of DPPH and synthesized com-
pounds was 0.1 mM). The mixture was shaken vigorously
and allowed to stand for 30 min. After this, the absorb-
ance at 534 nm was determined and the percentage of
scavenging activity was calculated using the following
formula:
Figure 1 Cyclic voltammograms of compounds 5d, 5b and
5e (1 × 10–3 M) in CH3CN, scan rate 100 mV·s–1.
Scavenging activity = {[(Ab+ As) – Am]/Ab}×100%
Ab: absorbance of 0.1 mM ethanolic solution of DPPH
at 534 nm,
As: absorbance of 0.1 mM ethanolic solution of test
compound at 534 nm,
Am: absorbance of ethanolic mixture of the drug and
DPPH at 534 nm.
Trolox was used as reference compound. All tests and
analyses were done on triplicate and averaged on three
samples. The results are given in Scheme 4.
Among the compounds from the 3-(5-aryl-4,5-dihydro-
1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-one 4 series,
4b showed moderate antioxidant activity.
The activity exhibited by the compound 4e was the
highest. In addition the experimental data show that
compound 4a scavenges free radical better than Trolox.
According to the experimental results, we notice that
increasing the concentration of pyrazole percentage of
inhibition reaches 90% for a concentration about 1 µM
for all the synthesized products. Thus, we can conclude
that substituents on the aryl group do not influence sig-
nificantly the anti-oxidant activity.
One parameter that has been introduced recently for
the interpretation of the results from the DPPH method is
the efficient concentration or EC50 value (otherwise called
the IC50 value), which is defined as the concentration of
substrate that causes 50% loss of the DPPH activity
(color) and corresponds to the endpoint of the titration.
In all cases, any residual (yellow) color from the reduced
form or any non specific absorbance from the sample
should be considered in defining the ‘‘endpoint’’ of the
titration, i.e., the 50% point. Additionally, this IC50 pa-
rameter has also the drawback that the higher the anti-
oxidant activity, the lower is the value of EC50.
The EC50 values exhibited by 3-(5-aryl-4,5-dihydro-
1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-one 4, 5 are
summarized in the following Table 2.
From inspection of Table 2, it is evident that pyra-
zoles 4,5 are more active than trolox.
Table 2. The EC50 values exhibited by 3-(5-aryl-4,5-dihydro-
1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-one 4, 5
Compounds 4, 5 CI50 (µmol.L–1).
4a 4,8
4b 5
4c 3,8
4d 4,2
5a 3,8
5b 3,2
5c 2,7
5d 3
trolox 7,5

A. S. AL-AYED 91
Scheme 4. Scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical of compounds 4, 5.
1.2.2.2 ABTS radical cation decolorization assay
The potential of 3-(5-aryl-4,5-dihydro-1H-pyrazol-3-
yl)-4-hydroxy-2H-chromene-2-one 4 to scavenge free
radicals was also assessed by checking their ability to
quench ABTS+. Scheme 5 depicts the concentration-
dependent decolourization of ABTS+.
ABTS radical-scavenging activity of 3-(5-aryl-4,5-dihy-
dro-1H-pyrazol-3-yl) -4-hydrox y-2H-chro mene-2-one 4,
5 was determined according to Re et al. 30]. The ABTS+.
Cation radical was produced by the reaction between 5 ml
of 14 mM ABTS solution and 5 ml of 4.9 mM potassium
persulfate (K2S2O8) solution, stored in the dark at room
temperature for 16 h. Before use, this solution was di-
luted with ethanol to get an absorbance of 0.700 ± 0.020

A. S. AL-AYED
92
at 734 nm. In a final volume of 1 ml, the reaction mix-
ture comprised 950 µl of ABTS ± solution and 50 µl of
the pyrazoles 4, 5 at various concentrations. The reac-
tion mixture was homogenized and its absorbance was
recorded at 734 nm. Ethanol blanks were run in each
assay, and all measurements were done after at least 6
min. Similarly, the reaction mixture of standard group
was obtained by mixing 950 ll of ABTS+ solution and 50
µl of TROLOX. As for the antiradical activity, ABTS
sca- venging ability was expressed as EC50 (<mu> g/ml).
The inhibition percentage of ABTS radical was calcu-
lated using the following formula:
ABTS scavenging effect % = {[(A0 – A1)]/AO} ×100%
where A0 is the absorbance of the control at 30 min, and
A1 is the absorbance of the Sample at 30 min. All sam-
ples were analyzed in triplicate.
As shown for DPPH scavenging, these data indicate
the higher capacity of 3-(5-aryl-4,5-dihydro-1H-pyrazol-
3-yl)-4-hydroxy-2H-chromene-2-one 4, 5 to quench ABTS+
as compared to the synthetic antioxidant TROLOX.
The variation of the percentage of inhibition (PI) is
almost constant starting from a value of the concentra-
tion equal to 1, 34 mM. In addition, the synthesized
products 5 have an antioxidant activity better than Trolox.
Indeed, the antioxydant capacity seems to be attenuated
Scheme 5. Scav enging abili ty on ABTS radical of comp o u n ds
4, 5.
when the concentration increases in the medium. This
can be explained by the existence of the peroxides sites
which are susceptible for oxidizing when the concentra-
tion increases. We have just shown that the synthesized
pyrazoles derivatives 4, 5 have a good antioxidant activ-
ity under weak concentration, but it proves to be neces-
sary to determine the reaction time necessary to highlight
the antioxidant effect to be able to use these derivatives
in pharmay.
The EC50 values exhibited by 3-(5-aryl-4,5-dihydro-
1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-one 4, 5 are
summarized in the following Table 3.
The 3-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-
2H-chromene-2-one 4, 5 were shown to be efficient an-
tioxidants. They showed higher free radical scavenging
activity than Trolox scavenging activities.
These compounds have a remarkable capacity oxidiz-
ing which explains their susceptibility to fix free radicals
DPPH and ABTS+.
2. Antibacterial Activity
The antibacterial activity of 3-(5-aryl-4,5-dihydro-1H-
pyrazol-3-yl)-4-hydroxy-2H-chromene-2-one 4 was as-
sessed by the agar disk diffusion assay [28] against five
human pathogenic bacteria: Gram-positive including Sta-
phylococcus aureus (CIP 7625), Staphylococcus aureus
and Gram-negative bacteria including Escherichia coli
(ATCC 25922), Pseudomonas aeruginosa (ATCC 27853)
(CIP 76110) and Klebsiella pneumonia CIP 104727. The
bacterial strains were first grown on Muller Hinton me-
dium at 37˚C for 24 h prior to seeding onto the nutrient
agar. The antibacterial activity was assessed by measur-
ing the zone of growth inhibition surrounding the discs
and compared with the known antibiotic gentamycin.
Standard discs of gentamycin (10 UI) served as positive
antibiotic controls according to CASFM 2005 guidelines.
Discs with 10 µl of pure methanol were used as negative
controls. The results are given in Table 4 below.
Table 3. The EC50 values exhibited by 3-(5-aryl-4,5-dihydro-
1H-pérazol-3-yl)-4-hydroxy-2H-chromène-2-one 4, 5.
Compounds 4, 5 CI50 (g·l–1)
4a 0.72
4b 0.98
4c 0.78
4d 1.17
5a 0.938
5b 1
5c 0.773
5d 0.72
Trolox 0.549

A. S. AL-AYED 93
Table 4. Antibacterial activity spectrum of compounds 5a-e.
Indicator organism inhibition
zone (mm) compounds
34 5a
27 5b
28 5c
33 5d
34 5e
Staphylococcus aureus (CIP 7625)
24 - 28 Gentamycin
26 5a
28 5b
27 5c
33 5d
34 5e
Staphylococcus aureus*
24 Gentamycin
30 5a
27 5b
35 5c
32 5d
31 5e
Escherichia coli ATCC 25922
22 - 26 Gentamycin
25 5a
27 5b
31 5c
30 5d
28 5e
Klebsiella pneumonia CIP 104727
21 Gentamycin
30 5a
26 5b
34 5c
33 5d
32 5e
PseudomonasAeruginosa 27853
(CIP 76110)
15 - 22 Gentamycin
The residual antibacterial activity of the compounds was
tested by disc diffusion assay against the indicator strain in
LB medium at 28˚C
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
Methicillin-resistant clinical isolates
An examination of the data reveals that all the com-
pounds showed antibacterial activity ranging from 25 to
100 μg ml–1. The compounds 5a and 5e were highly active
against all the five organisms employed. Compound 5c
was highly active against E. coli. From the screened results,
it is observed that the presence of methoxy/NO2 group at
the phenyl ring increases the antibacterial activity. The
highest activity was found in compound 5b bearing a
methoxy group at 4-position.
3. Conclusions
A new versatile synthetic route to 3-(5-aryl-4,5-dihydro-
1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-one 4, 5 by
the treatment of 4-hydroxycoumarine with different re-
agents is described. The method is easy, rapid and yielded
the title compounds 4, 5 in good yields. The structures of
the novel compounds were verified by, IR 1D/2D NMR
spectroscopy. All the newly synthesized compounds were
screened for their antibacterial and antioxidant activities.
Among the screened samples, compounds 5a and 5b
showed excellent antibacterial activity against E. coli.
Compounds with 4-phenyl, 4-methoxyphenyl, 4-fluoro-
phenyl and 4-nitrophenyl substituents in the pyrazole
ring exhibited higher antioxidant activity than trolox
while the pyrazole bearing a p-methoxy substituent in the
phenyl ring exhibited enhanced antioxidant activity.
4. Experimental Section
4.1. General
All reactions were magnetically stirred. Commercially
available reagents were used without further purification.
All chemicals were supplied from Aldrich, Merck and-
Fluka Co. Melting points were determined by open cap-
illary method and were uncorrected.
All reactions were monitored by thin layer chroma-
tography (TLC). Compounds were visualized with UV
light at 254 and 365 nm. Melting points were measured
on a WRX-1S instrument. Infrared (IR) spectra were re-
corded with a Perkin-Elmer spectrum one B spectrometer.
1H and 13C{1H} NMR spectra were recorded on a Var-
ian-Unity spectrometer at 300 MHz using tetramethylsi-
lane (TMS) as an internal standard. Cyclic voltammetry
(CV) was performed on a BAS 100 BW electrochemical
workstation. All CV measurements were carried out us-
ing tetrabutylammonium bromide (C4H12BrN) as a sup-
porting electrolyte, purging with nitrogen prior to con-
duct the experiment. Platinum wire (MF-2013) was used
as a working electrode, Ag/AgCl as a reference electrode,
and another platinum wire (MF-1032) as a counter elec-
trode.
3-Acetyl-4-hydroxycoumarin
To a solution of 4-hydroxy-2H-chromen-2-one (3.0 g,
1.86mmol) in acetic acid (16 ml) phosphorus oxych-
loride (5.6 ml) was added. The mixture was heated at
reflux for 30 min. After cooling to room temperature, the
precipitate which separated out was collected by filtra-
tion and recrystallized from ethanol to give 3-acetyl-4-
hydroxy-2Hchromen-2-one as white needles. Yield 2.7 g
(90%); Mp = 135˚C. IR spectrum, ν cm–1: 3185 (OH);
1705 (CO); 1700 (O-CO lactone). 1H NMR spectrum
(CDCl3). δ: 2.72 (3H, s, CH3); 7.98 (1H, s, H-5); 7.95
(1H, dd, 3J 7.8, 8.35, 4J 6.8, 1.2 Hz, H-8); 7.1 - 7.4 (2H,
m, H-6 + H-7); 17.7 (1H, s, OH).13C{1H} NMR spec-
trum (CDCl3),  : 29.9 (CH3); 178.5 (CO);159.8 (C-4);
154.6 (C-2); 101.3 (C-3); 115.0 - 136.0 (Carom).

A. S. AL-AYED
94
General procedure for the preparation of the cou-
marinic chalcones 4a-i
3-acetyl-4-hydroxy-2Hchromen-2-one (0.031 mol) and
the substituted aromatic aldehyde (0.03 mol) were dis-
solved 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
Yield 65%; mp 234˚C. IR spectrum, ν cm–1: 1683 (C=O
lactone), 1608 (C=N), 3230 (NH). 1H NMR spectrum
(DMSO-d6, 300 MHz, tamb)
3-((2E)-3(phenyl)prop-2-enoyl)-2H-chromen-2-one: 3a
Yield 85%; mp 265˚C. IR spectrum, ν cm–1: 1490 (C=O),
1728 (O-C-O), 1529 (C=C). 1H NMR spectrum (CDCl3).
δ ppm: 6.5 - 8.3 (m, 11H, Harom, Heth); 18.56 (s, 1H, OH).
13CNMR spectrum (CDCl3). δ ppm: 116.9 (C3); 135.8
(C2); 147.1 (C4); 134.5 (Cethyl)
3-((2E)-3(4-fluorophenyl)prop-2-enoyl)-2H-chromen-
2-one: 3b
Yield 80%; mp 215˚C. IR spectrum, ν cm–1: 1494 (C=O),
1716 (O-C-O), 1531 (C=C). 1H NMR spectrum (CDCl3,
400MHz). δ ppm: 6.51 - 8.21 (m, 10H, Harom+éthyl ); 18,4(s,
1H, OH). 13CNMR spectrum (CDCl3). δ ppm: 100.9 (C3);
154.8 (C2); 166 (C4); 181.5 (CO); 136.2 (Céthyl1); 131.5
(Céthyl2); 116.5 - 131.51 (Carom). NMR 19F (CDCl3, 400
MHz, tamb) ppm: –107.8
*3-((2E)-3(2, 5-dimethylphenyl)prop-2-enoyl)-2H-chro-
men-2-one: 3c
Yield 75%; mp 224˚C. IR spectrum, ν cm–1: 1490 (C=O),
1720 (O-C-O), 1527 (C=C). 1H NMR spectrum (CDCl3).
δ ppm: 2,41 (s, 1H, CH3), 3,21 (s, 3H, CH3), 6.82 – 8.21
(m, 9H, Harom+éthy); 13,81 (s, 1H, OH). 13CNMR spectrum
(CDCl3). δ ppm: 91.4 (C3); 135.8 (C2); 161.4 (C4); 139.1
(Céthyl), 134.1 (Céthy2); 116.4 – 133.2 (Crom), 176.2 (CO)
*3-((2E)-3(4-methoxyphenyl) prop-2-enoyl)-2H-chromen-
2-one: 3d
Yield 75%; mp 194˚C. IR spectrum, ν cm–1: 1494 (C=O),
1708 (O-C-O), 1595 (C=C). 1H NMR spectrum (CDCl3).
δ ppm: 3.84 (s, 3H, OCH3); 6.92 (d, 1H, CH); 8.25 (d, 1H,
CH); 7.25 - 8.08 (m, 8H, Harom); 18.05 (s, 1H, OH).
13CNMR spectrum (CDCl3). δ ppm: 55.4 (OCH3); 114.4
(C3); 116.8 – 131.3 (Carom); 135.6 (C2); 147.48(C4); 162.4
(CO).
*3-((2E)-3(4-nitrophenyl)prop-2-enoyl)-2H-chromen-
2-one: 3e
Yield 72%; mp 194˚C. IR spectrum, ν cm–1: 1489 (C=O),
1712 (O-C-O), 1535 (C = C). 1H NMR spectrum
(CDCl3). δ ppm: 7.1 - 8.6 (m,1OH, Harom+ethyl); 18.4 (s1,
H, OH). 13CNMR spectrum (CDCl3). δ ppm: 98.7 (C3);
151.8 (C2); 178.7 (C4); 182.5 (CO); 151.86 (Cethyl1);
122.5 (Cethyl2).
3-(5-(phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy
-2H-chromene-2-ones: 4a

ppm: 1.75(d, 2H, CH2),
3.74 (t, 1H, CH), 6,82-7,27 (m, 9H, Harom). 13CNMR
spectrum (DMSO-d6, 75 MHz, tamb)

ppm: 40, 6 (CH2)
49,5 (CH), 91,1 (C3); 158,6 (C2); 166,4 (C4); 155,7 (C =
N), 121,5-127,1 (Carom).
3-(5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-
hydroxy-2H-c hromene-2-ones: 4b
Yield 70%; mp 220˚C. IR spectrum, ν cm–1: 1668 (C=O
lactone), 1612 (C=N), 3192 (NH). 1H NMR spectrum
(DMSO-d6, 300 MHz, tamb)

ppm: 1,76(d, 2H, CH2),
3.64 (t, 1H, CH), 6.79 – 7.35(m,8H, Harom). 13CNMR
spectrum (DMSO-d6, 75 MHz, tamb)

ppm: 40.2 (CH2)
48.7 (CH), 91.1 (C3); 158.5 (C2); 166.7 (C4); 155.2
(C=N), 120.8 - 128.3 (Carom). NMR 19F (DMSO-d6, 300
MHz, tamb) ppm: –139.26
3-(5-(2,5-dimethylphenyl)-4,5-dihydro-1H-pyrazol-3-
yl)-4-hydroxy-2H-chromene-2-ones: 4c
Yield 80%; mp 252˚C. IR spectrum, ν cm–1: 1683 (C=O
lactone), 1606 (C=N), 3230 (NH). 1H NMR spectrum
(DMSO-d6, 300 MHz, tamb)

ppm: 1.68 (d, 2H, CH2),
3,68 (t, 1H, CH), 2,34 (s, 6H, 2CH3), 6.85 - 7.32(m,
Harom). 13CNMR spectrum (DMSO-d6,75 MHz, tam )
b

ppm: 18.6 (CH3), 24.5 (CH3), 40.2 (CH2), 42.6 (CH),
91.7 (C3); 158.4 (C2); 167.6 (C4); 155.7 (C=N), 121.7 -
132.8 (Carom).
3-(5-(4-methoxyphényl)-4,5-dihydro-1H-pyrazol-3-yl)
-4-hydroxy -2 H -chr omene-2-ones: 4d
Yield 85%; mp 210˚C. IR spectrum, ν cm–1: 1668 (C=O
lactone), 1608 (C=N), 3207 (NH). 1H NMR spectrum
(DMSO-d6,300 MHz,tamb)

ppm: 3.84 (s, 3H, OCH3),
6.82 - 8.1 (m, 8H, Harom), 4.12 (d, 2H, CH2), 4,81 (t, 1H,
CH). 13CNMR spectrum (DMSO-d6, 75 MHz, tamb)

ppm: 58.2 (OCH3), 55.0 (CH), 43.7 (CH2), 91.4 (C3);
158.7 (C2); 161.6 (C4); 153.3 (C=N), 113.8 – 133.4
(Carom).
3-(5-(phenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-
4-hydroxy-2H-chromene- 2-one:5a
Yield 70%; mp 230˚C. IR spectrum, ν cm–1: 1668 (C=O
lactone), 1608 (C=N), 3110 (NH). 1H NMR spectrum
(DMSO-d6, 300 MHz, tamb)

ppm: 1.65 (d, 2H, CH2),
3.75 (t, 1H, CH), 6.42 - 7.35 (m Harom). 13CNMR
spectrum (DMSO-d6, 75 MHz, tamb)

ppm: 36.4 (CH2)
54.8 (CH), 92.3 (C3); 159.7 (C2); 167.8 (C4); 158.1
(C=N), 113.5 - 133.1 (Carom).

A. S. AL-AYED 95
3-(5-(4-fluorophenyl)-1-phenyl-4,5-dihydro-1H-pyraz
ol-3-yl)-4-h ydroxy-2H-chromene- 2-one: 5b
Yield 72%; mp 226˚C. IR spectrum, ν cm–1: 1668 1683
(C=O lactone), 1606 (C=N), 3230 (NH). 1H NMR spe-
ctrum (DMSO-d6, 300 MHz, tamb)

ppm: 1.62 (d, 2H,
CH2), 3.65 (t, 1H, CH), 6.35 – 7.45 (m Harom). 13CNMR
spectrum (DMSO-d6,75 MHz, tamb)

ppm: 35.3 (CH2)
52.7 (CH), 92.1 (C3); 159.2 (C2); 167.8 (C4); 152.6 (C=N),
120.5 - 134.1 (Carom). NMR 19F (DMSO-d6, 300 MHz,
tamb) ppm: –129,42
3-(5-(2,5-dimethylphenyl)-1-phenyl-4,5-dihydro-1H-p
yrazol-3-yl)-4-hydroxy-2H-chromene-2-one: 5c
Yield 78%; mp 265˚C. IR spectrum, ν cm–1: 1681 (C=O
lactone), 1608 (C=N), 3220 (NH). 1H NMR spectrum
(DMSO-d6, 300 MHz, tamb)

ppm: 1,63 (d, 2H, CH2),
3.68 (t, 1H, CH), 6.35 – 7.68 (m Harom). 13CNMR spec-
trum (DMSO-d6, 75 MHz, tamb)

ppm: 35.3 (CH2)
52.8 (CH), 92.1 (C3); 158.8 (C2); 168.4 (C4); 159.6
(C=N), 126.5 - 142.1 (Carom).
3-(5-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyr
azol-3-yl)-4-hydr ox y -2 H -chromene-2-one: 5d
Yield 75%; mp 216˚C. IR spectrum, ν cm–1: 1681 (C=O
lactone), 1608 (C=N), 3234 (NH). 1H NMR spectrum
(DMSO-d6, 300 MHz, tamb)

ppm: 1.62 (d, 2H, CH2),
3.68 (t, 1H, CH), 3.78 (s, 3H, CH3), 6.47 – 7.42 (m
Harom). 13CNMR spectrum (DMSO-d6, 75 MHz, tamb)

ppm: 32.4 (CH2) 51.4 (CH), 55.8 (OCH3), 93.3 (C3);
156.4 (C2); 167.3 (C4); 152.5 (C=N), 113.4 – 132.6
(Carom).
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NOESY: Nuclear Overhauser effect spectroscopy
HMBC: Heteronuclear Multiple Bond Correlation experiment