Synthesis of new substituted chromen[4,3-c]pyrazol-4-ones and their antioxidant activities

Article abstract of DOI:10.3390/molecules161210292

A series of new coumarin derivatives 4 containing a 4-arylbut-3-en-2-one moiety were synthesized by condensation of 3-acetylcoumarin 1 with aryl aldehydes 2 in chloroform in the presence of piperidine. The interactions of 3-formyl-4-chlorocoumarin (3) with nitrogen-containg nucleophiles leading to the corresponding substituted chromen-[4,3- c]pyrazol-4-ones 5 are described. The structures of the obtained compounds were established on the basis of 1D NMR, 2D NMR and IR and further the compounds were evaluated for possible antioxidant activities. The coumarinic chalcone 4a has been found to be the most active (IC₅₀ = 2.07 μM) in this study.

Full text of DOI:10.3390/molecules161210292

Molecules 2011, 16, 10292-10302; doi:10.3390/molecules161210292
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis of New Substituted Chromen[4,3-c]pyrazol-4-ones and
Their Antioxidant Activities
Abdullah Sulaiman Al-Ayed *
College of Science and Arts at Ar-Rass, Qassim University, P.O. Box 53, Saudi Arabia;
E-Mail: salayedabdualla1@yahoo.com; Tel.: +966-505-142-736; Fax: +966-63-339-351
Received: 11 November 2011; in revised form: 28 November 2011 / Accepted: 29 November 2011 /
Published: 12 December 2011
Abstract: A series of new coumarin derivatives 4 containing a 4-arylbut-3-en-2-one moiety
were synthesized by condensation of 3-acetylcoumarin 1 with aryl aldehydes 2 in chloroform
in the presence of piperidine. The interactions of 3-formyl-4-chlorocoumarin (3) with
nitrogen-containg nucleophiles leading to the corresponding substituted chromen-[4,3-
c]pyrazol-4-ones 5 are described. The structures of the obtained compounds were
established on the basis of 1D NMR, 2D NMR and IR and further the compounds were
evaluated for possible antioxidant activities. The coumarinic chalcone 4a has been found to
be the most active (IC50 = 2.07 μM) in this study.
Keywords: coumarin derivatives; chalcone; antioxidant activities
1. Introduction
Coumarin derivatives constitute an important class of compounds with a wide range of biological
activities [1-3]. In particular, they are important as photochemotherapeutic agents that are used to treat a
variety of skin diseases [4]. They have been also found to exhibit antitumor [5], antioxidant [6] and
anti-inflammatory [7] properties. Some phenylcoumarins and chalcones have been proposed as
suppressors of LTR-dependent transcription, but the mechanism of action has not been fully
characterized [8] (+)-Calanolide A, a natural dipyranocoumarin, is also currently undergoing anti-AIDS
clinical trials [9]. Recent research suggests that the fusion of a chalcone moiety with the coumarin ring
appears quite promising for the synthesis of derivatives with enhanced TPA cross-sections [10].
In the course of our continuing interest in the synthesis of coumarin derivatives including
4-hydroxylcoumarins with antibacterial and antioxidant activities [11-13] we have extended our

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research to the synthesis and biological evaluation of new coumarinyl chalcones and substituted
chromen[4,3-c]pyrazol-4-ones as antibacterial and antioxidant agents. This synthesis, using the
3-acetyl-4-hydroxycoumarin (1) and 4-chloro-3-formyl coumarin (3) systems (Figure 1) via an easy
and rapid method that improves the product yields to a significant level, is reported here.
Figure 1. 3-acetyl-4-hydroxycoumarin and 4-chloro-3-formyl coumarin target molecules.
Cl
O
OH
O
H
CH3
O
O
O
O
3
1
2. Results and Discussion
For acetylation of the 4-hydroxycoumarin to give 3-acetyl-4-hydroxycoumarin (1), the method of
Dholakia et al. [14] was employed, using glacial acetic acid as acetylating agent in the presence of
POCl3. The reaction was rapid, without involving any kind of competition from the intramolecular
condensation of 4-hydroxycoumarin [15]. This compound was characterized by IR, 1H- and 13C-NMR.
1
The H-NMR shows the aromatic protons as a multiplet between 7.24 and 8.01 ppm. A singlet at
2.74 ppm was assigned to the methyl protons while the OH signal appeared at 17.72 ppm. This very
high chemical shift might be explained by an intermolecular hydrogen bond.
The synthesis of coumarinic chalcones was achieved in one step using a new pathway by refluxing
3-acetyl-4-hydroxy coumarin 1 with various aryl or heteroaryl aldehydes in the presence of piperidine
in chloroform. The reaction studied and the products obtained are depicted in Scheme 1.
Scheme 1. Synthesis of coumarinic chalcones 4.
OH
OH
O
O
CH3
a
H
+
R
O
O
O
1
O
2
b
OH
O
O
O
4
R
Reagents and conditions: (a) glacial acetic acid, POCl3; (b) CHCl3, piperidine, 80 °C.

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Scheme 1. Cont.
Aryl aldehydes substituent groups.
4a–i
R
a
b
c
d
e
Me
Br
2,3,4 OCH3
H
N(Me)2
In conventional chalcone synthesis methods, the time for completion of reactions at room
temperature is very long, ranging from 24 to 36 h [16,17]. A small alteration in reaction conditions,
using chloroform as solvent with a mild organic base, for example, piperidine, reduced the reaction
time in most cases, to 1–1.5 h. Moreover, the isolation of product 4 was facilitated.
All the products were obtained as solids and their purity was checked by thin layer chromatography
(eluant: hexane/ethyl acetate, 1/1. v/v). All the synthesized compounds have been characterized on the
1
basis of their physical data and spectral analysis. The H-NMR spectra are consistent with the
molecular structure 4. The 13C-NMR spectrum of 4c in DMSO showed two downfield signals at
δ 162.42 (ketone CO) and δ 157.41 (lactone CO) as well as one upfield signal at δ 55.48 (OCH3).
Measurement of the spectrum using the DEPT technique showed that the HC carbons of the coumarinic
ring appear at δ 134.5, 131.3, 125.6 and 124.11. The IR spectra of compounds 4a–i showed bands
resulting from the OH, (ketone) C=O and (lactone) (C=O) stretching in the region 3,305–3,320 cm−1,
1,670–1,710 cm−1 and 1,720–1,750 cm−1, respectively, in all the cases. All this evidence was
supportive of the formation of compounds 4a–i.
The coumarinic 4-arylbut-3-en-2-one structure was deduced from an analysis of HMBC spectra
which indicate that both ethylenic protons correlate with the ketone carbon atom via J2 and J3 coupling
constants, and C3 respectively. Like 3-acetyl-4-hydroxycoumarin, compounds 4a–i can exist in several
tautomeric forms. The most stable tautomers A and B are stabilized by intramolecular hydrogen
bonding (Scheme 2).
Scheme 2. Tautomeric forms of compounds 4.
H
H
O
o
O
o
O
O
O
O
R
R
B
A
A range of activities have been claimed to arise from the fusion of some coumarins with pyrazole
rings [18-20]. Morever substituted pyrazoles have recently been used as analytical reagents in the
complexation of transition metal ions [21,22]. We have attempted to exploit this behaviour of aldehyde

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groups in 4 chloro-3-formylcoumarin with the purpose of finding a satisfactory route by which to
synthesize substituted chromen[4,3-c]pyrazol-4(1H)-ones bearing hydrogen or alkyl groups on N-2.
The compound 3 was prepared from 4-hydroxycoumarin under Vilsmeier conditions (POCl3/DMF).
The literature [23,24] claims the formation of mixture of carbaldehyde 3 and 4-chlorocoumarin
without any indication of their ratio. Steinführer et al. [25] reported that the reaction mixture contained
a mixture of 4-chloro-3-coumarin carbaldehyde 3(65%) with 4-chlorocoumarin as a side product
(20%). After further optimization we could obtain up to 95% of the carbaldehyde 3. The reaction
pathway is depicted in Scheme 3.
Scheme 3. Synthesis of chromen[4,3-c]pyrazol-4(1H)-ones 5.
OH
Cl
O
N
RN
H
POCl3
DMF
RNHNH2
Ethanol, Et3N
O
O
O
3
O
O
5a-c
O
5
a
b
c
R
H
CH3
Ph
1
TLC was used to monitor the progress of the reaction. The spectroscopic data MS, IR and H-NMR
are in agreement with the structure of 4-chloro-3-formylcoumarin. The heating of 3-formyl-4-chloro-
coumarin 3 and the appropriate hydrazine nitrogen compounds in ethanol at reflux for 2 h led to the
quantitative formation of the substituted chromen[4,3-c]pyrazol-4-ones 5 in short times and in high
yields (67 to 89%). The proposed structures of the new substituted chromen[4,3-c]pyrazol-4(1H)-ones
5 were validated by their spectral data, which were consistent with available literature data for similar
substitution patterns in coumarin derivatives [26,27].
The 1H-NMR spectra of compound 5a, for example, showed the expected signals: An exchangeable
NH proton and the typical doublet for the coumarin 9-H in the δ 7.96–8.20 ppm range, validated by the
13C spectral pattern of the coumarin ring. All the chromen[4,3-c]pyrazol-4(1H)-ones 5a–c displayed IR
stretching at 1,711–1,742 cm−1 associated with lactone carbonyl groups, also confirmed by the signals
13
appearing between δ 155 and 162 ppm in the C-NMR spectra. The derivatives 5a can exist in α, β
and γ tautomeric forms, as depicted in Scheme 4.
Ring tautomerism is common in heteroaromatic compounds and has been widely studied, but
literature relating to the chromen[4,3-c]pyrazol-4(1H)-ones nucleus gave poor attention to this
tautomerism problem [28,29]. The authors of the cited references assign two opposite tautomeric
1
structures to the same compound and the H-NMR spectroscopic data for this product are not
very detailed.

Molecules 2011, 16
Scheme 4. Tautomeric forms of chromen[4,3-c]pyrazol-4(1H)-ones 5.
10296
N
N
N
N
N
HN
O
O
O
OH
O
O
α
β
γ
In our case the β tautomer can be ruled out because all the IR spectra of the chromen[4,3-c]
pyrazol-4(1H)-ones 5a–c, recorded in chloroform solution, showed lactone bands at 1,704–1,712 cm−1,
confirmed by typical carbonyl patterns in the 13C-NMR spectra. 1H- and 13C-NMR analyses show that
compounds 5 exist as the tautomeric form containing a proton on the N atom.
3. Antioxidant Activities
There is an increasing interest in antioxidants, particularly in those intended to prevent the
presumed deleterious effects of free radicals in the human body, and to prevent the deterioration of fats
and other constituents of foodstuffs. In both cases, there is a preference for antioxidants from natural
rather than from synthetic sources. There has therefore been a parallel increase in the use of methods
for estimating the efficiency of such substances as antioxidants.
One such method that is currently popular is based upon the use of the stable free radical
diphenylpicrylhydrazyl (DPPH). The purpose of our study was to examine the use of the parameter
“EC50” (equivalent concentration to give 50% effect) which is currently used in the interpretation of
experimental data from the method.
When a solution of DPPH is mixed with that of a substance that can donate a hydrogen atom, this
gives rise to the reduced form with the loss of this violet colour (although there would be expected to
be a residual pale yellow colour from the picrylgroup still present). Representing the DPPH radical by
Z• and the donor molecule by AH, the primary reaction is:
Z + AH = ZH + A
(1)
where ZH is reduced form and A• is free radical produced in this first step. This latter radical will then
undergo further reactions which control the overall stoichiometry, that is, the number of molecules of
DPPH reduced (decolorized) by one molecule of the reductant.
The reaction (1) is therefore intended to provide the link with the reactions taking place in an
oxidizing system, such as the autoxidation of a lipid or other unsatured substance; the DPPH molecule
Z• is thus intended to represent the free radicals formed in the system whose activity is to be
suppressed by the substance AH• Representing the DPPH radical by Z• and the coumarinic chalcones
by ROH, the initial reaction is then Z• + ROH= ZH+ RO• [1], the free radical RO• Evidently then
reacts with another molecule of the same kind that was produced by a parallel reaction to (1)
RO• + RO• = RO-OR [2]. This therefore leads to the observed reduction of two molecules of DPPH by
two molecules of coumarinic chalcones, that is, a 1:1 stoichiometry. One parameter that has been

Molecules 2011, 16
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introduced recently for the interpretation of the results from the DPPH method, is the efficient
concentration or EC50 value (otherwise called the IC50 value), defined as the concentration of substrate
that causes 50% loss of the DPPH activity (colour), corresponding to the endpoint of the titration. It
should be noted that in all cases, any residual (yellow) colour from the reduced form or any
non-specific absorbance from the sample has to be taken into account in defining the “endpoint” of the
titration, or the 50% point, this EC50 parameter also has the drawback that the higher the antioxidant
activity, the lower is the value of EC50. This is a disadvantage particularly when results are presented
graphically as a bar chart even if the same data are available in numerical forms. The reported
derivatives 4a–i were tested for their antioxidant. The corresponding IC50 values are summarized
in Table 1.
Table 1. The EC50 values exhibited by coumarinic derivatives 4.
Compounds 4a–i
EC50 (μM)
2.07
4a
4b
2.25
4c
2.29
4d
2.30
4e
2.35
1
2.35
3
2.45
Trolox
2.30
Compounds 4c and 4f showed potent antioxidant activity, while coumarinic chalcone 4f was
inactive, even at a concentration of 3.21 mΜ. Compound 4e proved to be the most active compound in
this study. Comparing the activity of compounds 4a–c, 4e and 4g it was concluded that there was no
substantial difference when we change the nature of the group R.
4. Experimental
4.1. General
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 °K in CDCl3 or DMSO d-6. 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), some combinations of these were made by DEPT editing of the spectra. 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
MS-spectra were recorded on a AEI MS 902 S electron ionization spectrometer (EI = 70 eV). The
absorption spectra were measured on a Beckmann K25 spectrophotometer.

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4.2. Materials
1,1-Diphenyl-2-picrylhydrazyl (DPPH) was obtained from Sigma. All other chemicals were of
analytical grade purity. The 4-hydroxycoumarin, aromatic aldehydes and nitrogen binucleophiles were
purchased from Fluka. DMF were purified, dried and distilled over CaH2 prior to use.
4-Chloro-3-coumarincarbaldehyde (3). To a stirred mixture of 4-hydroxycoumarin (9.72 g, 0.06 mol)
in anhydrous DMF (46.2 mL, 0.6 mol) were added dropwise POCl3 (27.6 g, 0.18 mol) at –10° to
–5 °C. The reaction mixture was then stirred for 1 h at room temperature and heated and stirred for 2 h
at 60 °C. After the reaction was completed, the mixture was poured onto crushed ice (200 g) under
vigorous stirring. After storing the mixture overnight at 0 °C the pale yellow solid was collected by
filtration and washed successively with aquous Na2CO3 (5%) and water, and then was air–dried.
4-chlorcoumarin (2.50 g, 20%) was separated by Soxhlet extraction as the second product.
Recrystallization from acetone gave 8.99 g (72%) of 2 as a pale yellow powder with mp 115–120 °C;
1H-NMR δ 10.39 (1H, s, CH=O), 8.19–7.40 (4H, m, Ar-H); 13C-NMR δ 186.81 (11-C), 158.44 (2-C),
153.28 (4-C), 153.27 (9-C),135.68 (7-C), 127.65 (5-C), 125.56 (6-C), 118.39 (10-C), 118.22 (3-C),
117.20 (8-C); IR ν 2920, 2874, 1720, 1702, 1603, 1587, 1541 cm–1; MS, m/z: 208 (MH+, 11), 182 (31),
180 (100), 154(31), 152 (91), 124 (20), 101 (11).
4.3. General Procedure for the Preparation of 3-[3-Substituted phenyl prop-2-enoyl) chromen-2-ones 4a–g
3-Acetyl-4-hydroxyxcoumarin (0.031 mol) and the appropriate substituted aromatic aldehyde
(0.03 mol) were dissolved in chloroform (30 mL). A catalytic amount of piperidine (0.02 mol) was
added and the reaction mixture was refluxed for 1.5 h. The chloroform was distilled out and the
residue was washed with methanol.
4.4. Characterization of Newly Synthesized Coumarinic Chalcones
3-((2E)-3-(p-Tolyl)prop-2-enoyl)-2(H)-chromen-2-one (4a). Solid (yield 75%), mp = 138 °C, IR: ν
3168 (-OH), 1622 (>C=O), 1577 (C=C), 1028(s) (sym) (C-O-C); 1H-NMR: δ (ppm) 2.84 (s, 3H, CH3);
7.28 (s, 1H), 7.60 (s, 1H), 7.2–8.2 (m, 8H, Ar-H), 17.82 (s, 1H, OH); 13C-NMR (ppm): 30.0 (OCH3);
178.4 (CO); 154.6 (C4); 135.6 (C2); 101.3–135.9 (Carom). C19H14O4 calc. C 74.50, H 4.57, O 20.91,
found C 74.40, H 4.60, O 20.90.
3-[(2E)-3-(4-Bromophenyl)prop-2-enoyl]-2(H)-chromen-2-one (4b). Solid (yield 85%), mp = 182 °C,
1
IR: ν 3168 (-OH), 1622 (>C=O), 1577 (C=C), 1028(s) (sym) (C-O-C); H-NMR: δ (ppm) 6.26–7.84
(m, 8H, Ar-H+Héthyl), 19.58 (s, 1H, OH); 13C-NMR (ppm): 191.2 (CO); 172.8 (C4); 172.1 (C2);
102.2–168.8 (Carom+Cethyl). C18H11O4Br calc. C 58.22, H 2.96, O 17.25, found C 58.30, H 2.90, O 17.30.
3-((2E)-3-(2,3,4-Trimethoxy-phenyl)prop-2-enoyl)-2(H)-chromen-2-one (4c). Solid (yield 83%),
1
mp = 193 °C, IR: ν 3368 (-OH), 1716(s) (>C=O), 1577 (C=C), 1018(s) (sym) (C-O-C); H-NMR: δ
(ppm) 7.30 (s, 1H), 7.51 (s, 1H) 6.90–7.96 (m, 7H, Ar-H), 19.50 (s, 1H, OH); 13C-NMR (ppm):
191.6 (CO); 59.7 (O-CH3); 59.8 (O-CH3); 60.0 (O-CH3) 103.47–153.3 (Carom); 164.8 (C4);
163.2 (C2); 102.8 (C3). C21H18O7 calc. C 65.96, H 4.71, O 29.31; found C 65.90, H 4.80, O 29.30.

Molecules 2011, 16
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3-[(2E)-3-(Naphtyl)prop-2-enoyl]-2(H)-chromen-2-one (4d). Solid (yield 80%), mp = 185 °C, IR: ν
1
3365 (-OH), 1718(s) (>C=O), 1578 (C=C), 1019(s) (sym) (C-O-C); H-NMR: δ (ppm) 7.30 (s, 1H),
7.51 (s, 1H), 6.75–7.92 (m, 11H, Ar-H), 19.40 (s,1H, OH); 13C-NMR (ppm): 192.6(CO);
102.47–154.2 (Carom); 164.6(C4); 164.2 (C2); 101.8 (C3). C22H14O4 calc. C 77.20, H 4.10, O 18.71;
found C 77.10, H 4.10, O 18.70.
3-((2E)-3-(4-Dimethylamino-phenyl)prop-2-enoyl)-2(H)-chromen-2-one (4e). Solid (yield 85%),
1
mp = 192 °C, IR: ν 3125 (-OH), 1712(s) (>C=O), 1550 (C=C), 1028 (sym) (C-O-C); H-NMR: δ
(ppm) 2.9 (s, 6H, CH3), 6.54–8.1 (m, 10H, Ar-H+Héthyl), 18.62 (s, 1H, OH); 13C-NMR (ppm):
191.0 (CO); 40.1 (CH3-N); 102.8–142.9 (Carom); 179.2 (C4); 162.2 (C2); 102.8 (C3). C20H17O4N calc.
C 71.64, H 5.1, O 19.10, N 4.17; found C 71.60, H 5.10, O 19.30, N 4.20.
4.5. Synthesis of Aryl(alkyl)chromeno[4,3-c]pyrazol-4(1H)-one 5
The aldehyde 3 (0.41 g, 2 mmol) dissolved on boiling in ethanol (10 mL) and was then cooled to
15–20 °C. A solution prepared from aryl or alkylhydrazine hydrochloride (0.29 g, 2 mmol) and
triethylamine (4 mmol) in 60%) ethanol (10 mL) was slowly added dropwise so that the temperature of
the reaction mixture did not exceed 25 °C. After addition of the reagent was complete a yellowish
precipitate formed rapidly. The precipitate was filtered off and recrystallized from ethanol and then
twice more from DMF to give fine colourless needles
1H-Chromeno[4,3-c]pyrazol-4-one (5a). Solid (Yiled 67%), mp = 183 °C; IR: ν 3368 (-NH), 1716(s)
1
(lactone >C=O), 1577 (C=C), 1018(s) (sym) (C-O-C); H-NMR: δ (ppm) 7.40 (s, 1H, Héthy),
7.13–7.46 (m, 4H, Ar-H), 13.2 (s, 1H, NH); 13C-NMR (ppm): 158.2 (C2); 102.1 (C3); 149.2 (C4);
146.7 (C=N); 122.1–151.2 (Carom). C10H5O2N2 calc. C 64.86, H 2.70, O 17.30, N 15.13; found C 64.80,
H 2.70, O 17.20, N 15.2.
1-Methyl-1H-chromeno[4,3-c]pyrazol-4-one (5b). Solid(Yiled 75%), mp = 184 °C; IR: ν 1720(s)
(lactone >C=O), 1578 (C=C), 1020(s) (sym) (C-O-C); 1H-NMR: δ (ppm). 3.5 (s, 3H, CH3), 6.4 (s, 1H,
Héthy); 7.13–7.45 (m, Ar-H), 13C-NMR (ppm): 157.2 (C2); 112.2 (C3); 144.6 (C4); 140.6 (Céthyl);
122.1–151.2 (Carom). C11H7O2N2 calc. C 60.53, H 6.27, O 33.20; found C 60.50, H 6.30, O 33.20.
1-Phenyl-1H-chromeno[4,3-c]pyrazol-4-one (5c). Solid (Yiled 89%), mp = 185 °C; IR: ν 1718(s)
1
(lactone >C=O), 1579 (C=C), 1022(s) (sym) (C-O-C); H-NMR: δ (ppm): 7.13–7.45 (m, Ar-H),
13
7.2 (Héthy) C-NMR (ppm): 158.2 (C2); 112.4 (C3); 144.2 (C4); 138.6 (Céthyl); 122.1–151.2 (Carom).
C16H10O2N2 calc. C 58.89, H 3.06, O 9.81, N 8.58; found, C 58.90, H 3.10, O 9.80, N 8.60.
4.6. The Experimental Procedure for the Antioxidant Evaluation
The DPPH radical 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 °C, absorbance was read at
520 nm wavelength. A mixture of DPPH solution (0.5 mL) and ethanol (0.5 mL) was taken as a

Molecules 2011, 16
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blank (absorbance is equal to zero). Inhibitory concentration (IC50) values denoting the concentration
(microgram of natural substance per milliliter of ethanol) required to scavenge 50% of DPPH radicals
were calculated. All measurements were performed in triplicate. Results were expressed in inhibition
percentage versus sample concentrations (mg/mL) at 30 minutes.
5. Conclusion
In summary, we developed a new and simple method for the synthesis of new coumarinyl chalcone
derivatives through a condensation reaction. Our improved synthesis of coumarinyl chalcones was
effective in terms of time and yields. The reaction conditions are simple, since they are not sensitive to
oxygen and water, which make it easy to operate at room temperature. We have shown a new synthetic
method by which to synthesize substituted chromen[4,3-c]pyrazol-4-ones 5 in good yields. The
flexibility of this methodology should provide access to many variously substituted coumarinyl
pyrazoles. Our synthesis of coumarinic derivatives allowed us to obtain and identify 12 compounds.
The presence of the coumarin nucleus endows this species with important pharmacological and
therapeutic interest. The antioxidant activities of these compounds against the stable free radical DPPH
show that these species are good source of compounds that could help to increase the overall
antioxidant capacity of an organism.
Acknowledgments
The author is thankful to Research Center, Scientific Research Deanship, and Qaseem University
for all the help received.
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Sample Availability: Samples of the compounds 4 and 5 are available from the authors.
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