Synthesis of 3-(3-methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one derivatives via a one-pot, three-component reaction

Article abstract of DOI:10.1080/00397911.2013.867507

An efficient synthesis of 3-(3-methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen- 2-one derivatives by the reaction of salicylaldehydes, 4-hydroxy-6-methyl-2H- pyran-2-one, and arylhydrazine in acetonitrile under reflux condition and in the presence of piperidine is reported. This three-component reaction has some advantages such as ease of handling, good yields, and easy purification. All structures were confirmed by infrared, mass, ¹H NMR, and ¹³C NMR spectroscopy.

Full text of DOI:10.1080/00397911.2013.867507

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Synthesis of 3-(3-Methyl-1-aryl-1H-
pyrazol-5-yl)-2H-2-chromen-2-one
Derivatives via a One-Pot, Three-
Component Reaction
Abdolali Alizadeh a & Rashid Ghanbaripour a
a Department of Chemistry , Tarbiat Modares University , Tehran ,
Iran
Accepted author version posted online: 03 Apr 2014.Published
online: 14 May 2014.
To cite this article: Abdolali Alizadeh & Rashid Ghanbaripour (2014) Synthesis of 3-(3-Methyl-1-
aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one Derivatives via a One-Pot, Three-Component Reaction,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 44:11, 1635-1640, DOI: 10.1080/00397911.2013.867507
To link to this article: http://dx.doi.org/10.1080/00397911.2013.867507
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Synthetic Communications1, 44: 1635–1640, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.867507
SYNTHESIS OF 3-(3-METHYL-1-ARYL-1H-PYRAZOL-
5-YL)-2H-2-CHROMEN-2-ONE DERIVATIVES VIA A
ONE-POT, THREE-COMPONENT REACTION
Abdolali Alizadeh and Rashid Ghanbaripour
Department of Chemistry, Tarbiat Modares University, Tehran, Iran
GRAPHICAL ABSTRACT
Abstract An efficient synthesis of 3-(3-methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one
derivatives by the reaction of salicylaldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one, and arylhy-
drazine in acetonitrile under reflux condition and in the presence of piperidine is reported. This
three-component reaction has some advantages such as ease of handling, good yields, and easy puri-
fication. All structures were confirmed by infrared, mass, 1H NMR, and 13C NMR spectroscopy.
Keywords Arylhydrazine; coumarin; 4-hydroxy-6-methyl-2H-pyran-2-one; pyrazole;
salicylaldehyde
INTRODUCTION
Pyrazoles constitute a class of five-membered nitrogen-containing heterocyclic
compounds. Because of their wide spectrum of biological activities, such as antifun-
gal,[1] antiviral,[2] anticancer,[3] and anti-inflammatory[4] properties, they are widely
used in the pharmaceutical industry and medicinal chemistry and they are also impor-
tant core in natural products.[5,6] In addition, pyrazoles can act as kinase inhibitors
for treatment of type 2 diabetes and obesity, thrombopiotin mimetics, and antiangio-
genic agents.[7] Moreover, some pyrazoles are used in polymer and supramolecular
chemistry, in the food industry, and as ultraviolet stabilizers and cosmetic color-
ings.[8–10] Accordingly, synthesis of new pyrazole derivatives and investigation of their
biological activities have been considered by chemists.[11–13]
Coumarin moieties are a large group of oxygen-containing heterocycles that
are widely distributed in plants such as grasses, legumes, and fruits.[14] Coumarins
Received September 28, 2013.
Address correspondence to Abdolali Alizadeh, Department of Chemistry, Tarbiat Modares
University, P.O. Box 14115-175, Tehran, Iran. E-mail: aalizadeh@modares.ac.ir
Color versions of one or more of the figures in the article can be found online at www.tandfonline.
com/lsyc.
1635

1636
A. ALIZADEH AND R. GHANBARIPOUR
possess a wide range of biological activities including anticoagulant,[15] inhibition of
HIV-1 protease,[16] hypnotic,[17] anti-inflammatory,[18] and antihelminthic.[19] Besides
the biological applications, coumarins have been used in laser dyes, optical data stor-
age devices, optical brightners, and solar cells.[20,21] Although many methods have
been reported for the synthesis of coumarins, the development of novel strategies
for synthesis of new coumarin derivatives is still required.[22–25]
We are interested in examining the reaction of salicylaldehydes 1, 4-hydroxy-6-
methyl-2H-pyran-2-one, and arylhydrazines 2 to synthesize new coumarins contain-
ing pyrazole substitutions.
RESULTS AND DISCUSSION
In continuation of our studies on the synthesis of new heterocyclic com-
pounds,[26–28] we decided to synthesize coumarin derivatives including pyrazole-
substituted derivatives by the reaction of salicylaldehydes 1, 4-hydroxy-6-methyl-
2H-pyran-2-one, and arylhydrazines 2. Our new synthetic route is shown in Scheme 1.
The reaction of salicylaldehydes 1, 4-hydroxy-6-methyl-2H-pyran-2-one, and
arylhydrazine 2 was performed in acetonitrile within 3 h in the presence of one drop
of piperidine to produce 3-(3-methyl-1-aryl-1H-pyrazol-5-yl)-2H-chromen-2-ones 3
in good yields (Table 1).
The structures of compounds 3a–f were elucidated from their elemental
1
analysis, infrared (IR), and high-field H and 13C NMR spectra. The IR spectrum
of 3a showed absorption bands due to the carbonyl group stretching frequency at
1724 cmꢀ1 and absorption bands at 1602, 1497, 1464, and 1106 cmꢀ1 assigned to
=
the C C and C-O groups, respectively. The mass spectrum of this compound displays
the molecular ion peak at m=z 302 as a base peak, which is in agreement with the
1
proposed structure. The H NMR spectrum of 3a showed three singlet signals for
methyl, CH of the pyrazole ring, and CH of the coumarin ring groups (2.41, 6.63,
Scheme 1. Synthesis of 3-(3-methyl-1-aryl-1H-pyrazol-5-yl)-2H-2-chromen-2-one derivatives.
Table 1. 3-(3-Methyl-1-aryl-1H-pyrazol-5-yl)-2H-chromen-2-ones 3
Entry
R1
R2
Ar
Product
Yield (%)
1
2
3
4
5
6
H
H
H
Br
H
Ph
Ph
3a
3b
3c
3d
3e
3f
60
73
69
89
84
80
OCH3
Br
Br
Ph
Ph
Br
Br
Cl
4-Me-C6H4
Ph
Cl

(1H-PYRAZOL-5-YL)-2H-2-CHROMEN-2-ONE
1637
Scheme 2. Plausible mechanism for the formation of products 3a–f.
and 7.48 ppm), and one doublet, two multiplets, and one triplet of doublet for
aromatic hydrogens [7.28 (3J ¼ 6.0), 7.33–7.35, 7.40–7.42, and 7.55 (3J ¼ 8.0,
4J ¼ 1.6)], respectively. The 1H-decoupled 13C NMR spectrum of 3a showed 17
distinct resonances in agreement with the suggested structure.
According to these results, a plausible mechanism for the sequential three-
component reaction is proposed on the basis of known reactions[29,5] (Scheme 2).
The formation of product 3 can be explained by initial condensation between
salicylaldehyde and 4-hydroxy-6-methyl-2H-pyran-2-one in the presence of piperi-
dine to afford the desired 3-acetoacetylcoumarin 5. Then the intermediate 5 can
condense with an arylhydrazine and tautomerize to give intermediate 7. Finally, intra-
molecular cyclization and dehydration of compound 7 give the product 3 in good
yields. To evaluate the proposed mechanism, 3-acetoacetylcoumarin 5a was synthe-
1
sized separately and its structure has been confirmed by H NMR and 13C NMR
spectroscopies. In another attempt, the reaction between compound 4a and phenylhy-
drazine gave the desired product 3a.
EXPERIMENTAL
The salicylaldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one and arylhydrazines,
were obtained from Merck (Germany) and Fluka (Switzerland) and were used
without further purification. Melting points were measured on an Electrothermal
9100 apparatus. Elemental analyses for C, H, and N were performed using a Heraeus
CHN-O-Rapid analyzer. Mass spectra were recorded on a Finnigan-Matt 8430 mass
spectrometer operating at an ionization potential of 70 eV. 1H and 13C NMR spectra
were measured (CDCl3 solution) with a Bruker DRX-400 Avance spectrometer
at 400.13 and 100 MHz, respectively. IR spectra were recorded on a Shimadzu
IR-460 spectrometer and absorbencies are reported in centimetersꢀ1
.

1638
A. ALIZADEH AND R. GHANBARIPOUR
Typical Procedure for Preparation of 3-(3-Methyl-1-phenyl-1H-
pyrazol-5-yl)-2H-chromen-2-one (3a)
A solution of salicylaldeyde (1a, 0.122 g, 1 mmol) and 4-hydroxy-6-methyl-2H-
pyran-2-one (0.126 g, 1 mmol) in acetonitrile (5 ml) and one drop of piperidine were
magnetically stirred for 1 h at reflux. Then phenylhydrazine (2a, 0.108 g, 1 mmol) was
added, and the solution was magnetically stirred for 2 h at reflux. After completion,
the reaction was monitored by thin-layer chromatography (TLC), the solvent was
evaporated, and the residue was purified by column chromatography over silica
gel using n-hexane=ethyl acetate (9:1) as eluent to afford the pure product 3a.
3-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (3a)
Yield: 181 mg (60%); white powder; mp ¼ 126–127 ꢁC. IR (KBr): 1724 (CO2),
1602, 1497, and 1464 (Ar), 1106 (C-O) cmꢀ1
.
1H NMR (400.13 MHz, CDCl3):
3
dH ¼ 2.41 (3H, s, CH3), 6.63 (1H, s, CH of pyrazole), 7.28 (1H, d, JHH ¼ 6.0 Hz,
CHpara of Ph), 7.33–7.35 (4H, m, CH of Ar), 7.40–7.42 (4H, m, CH of Ar), 7.48
3
4
(1H, s, CH4 of chromene), 7.55 (1H, td, JHH ¼ 8.0 Hz, JHH ¼ 1.6 Hz, CH of Ar).
13C NMR (100.6 MHz, CDCl3): dC ¼ 13.6 (CH3), 110.2 (CH3 of pyrazole), 116.7
(CH8 of chromene), 118.6 (C3 of chromene), 118.9 (C4a of chromene), 124.7 (CH6
of chromene), 124.7 (2 CHortho of Ph), 127.7 (CH5 of chromene), 128.2 (CHpara of
Ph), 129.3 (2 CHmeta of Ph), 132.2 (CH7 of chromene), 136.3 (C5 of pyrazole),
140.2 (Cipso-N of Ph), 142.2 (CH4 of chromene), 149.6 (C3 of pyrazole) 153.6 (C8a
of chromene), 159.0 (CO2). MS (EI, 70 eV): m=z (%) ¼ 302 (Mþ, 100), 285 (19), 273
(62), 232 (21), 204 (34), 151 (25), 139 (28), 115 (33), 102 (28), 91 (34), 77 (77). Anal.
Calcd. for C19H14N2O2 (302.33): C, 75.48; H, 4.67; N, 9.27%. Found: C, 75.37; H,
4.75; N, 9.20%.
CONCLUSION
In summary, we have disclosed a concise approach to the synthesis of 3-(3-
methyl-1-aryl-1H-pyrazol-5-yl)-2H-chromen-2-ones by a one-pot and sequential
three-component reaction of salicylaldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one,
and arylhydrazines. Good yields, inexpensive starting materials, and simple
performance are the main aspect of the present method. Because of the importance
of coumarins and pyrazoles, the present methods can be considered for biological
evaluation in the near future.
FUNDING
Financial support of this research from Tarbiat Modares University, Iran, is
gratefully acknowledged.
SUPPORTING INFORMATION
Full experimental details and 1H and 13C NMR spectra can be accessed on the
publisher’s website.

(1H-PYRAZOL-5-YL)-2H-2-CHROMEN-2-ONE
1639
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