Microwave assisted synthesis of arylpyrazoles using montmorillonite K-10

Article abstract of DOI:10.14233/ajchem.2013.13306

Montmorillonite K-10 clay catalyzed Friedlander condensation of Baylis-Hillman adducts with phenyl hydrazine hydrochloride afforded 1,5-diarylpyrazoles.

Full text of DOI:10.14233/ajchem.2013.13306

Asian Journal of Chemistry; Vol. 25, No. 4 (2013), 2339-2340
http://dx.doi.org/10.14233/ajchem.2013.13306
NOTE
Microwave Assisted Synthesis of Arylpyrazoles Using Montmorillonite K-10
FARHAD HATAMJAFARI
Department of Chemistry, Faculty of Science, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
Corresponding author: E-mail: f_hatamjafari@tonekaboniau.ac.ir
(Received: 22 December 2011;
Accepted: 29 October 2012)
AJC-12350
Montmorillonite K-10 clay catalyzed Friedlander condensation of Baylis-Hillman adducts with phenyl hydrazine hydrochloride afforded
1,5-diarylpyrazoles.
Key Words: Arylpyrazole, Montmorillonite K-10, Microwave, Baylis-Hillman.
Heterocyclic compounds are valuable compounds and
many applications have been reported. Nitrogen containing
five and six membered heterocyclic compounds have been used
as a scaffold to synthesize numerous therapeutic molecules1.
We have synthesized a number of heterocyclic compounds2-6.
Arylpyrazole is an important class of organic compounds,
which received a considerable attention due to their wide range
of biological activities and widely used as pharmaceuticals,
agrochemicals, antiinflammatory, antiviral, antibacterial7-13. In
our ongoing research prompted by our interest in multiple
component reactions and as part of programs in the area of
heterocyclic compounds containing nitrogen14 and due to the
resultant pharmacological interest in compounds which belong
to the diarylpyrazoles, although this reaction done previously
in other conditions15,16, herein we report in a different condition
using microwave irradiation, one pot reaction, a short time
with high yields and easy separation of product for the cons-
truction of some 1,5-diarylpyrazole derivatives, via conden-
sation of Baylis-Hillman adduct and phenyl hydrazine under
microwave irradiation (Scheme-I).
IR spectra were measured on a Shimadzu IR-470 Spectro-
1
photometer. H and 13C NMR spectra were determined on
Bruker 300 DRX AVANCE instrument at 300 and 75 MHz,
respectively.
Synthesis of compounds 4a-e: In a reaction a mixture of
montmorillonite K10 (0.3 g) was placed in a mortar followed
by a Baylis-Hillman adduct (4a-e) (1 mmol) and phenyl
hydrazine hydrochloride (1 mmol) in 1,2-dichloroetane (5 mL).
These materials were then mixed using a pestle for ca. 4 min.
The homogenized mixture was transferred to a beaker and
irradiated with microwaves for 5 min. The progress of reaction
was monitored by TLC. The mixture was diluted with CH2Cl2
and washed with water and the organic layer was dried
(MgSO4). Evaporation of the solvent under vacuum provided
a residue which was purified by column chromatography
(hexan/ethyl acetate of 8/2) to afford the desired pyrazoles
(4a-e).
Compound 4a: Orange oil; IR: (KBr, νmax, cm-1): 3056,
2974, 1603, 1593, 1495; 1H NMR (300 MHz, CDCl3): 1.36 (t,
J = 7.6 Hz, 3H), 1.94 (s, 3H), 2.75 (q, J = 7.6 Hz, 2H), 7.21-
7.26 (m, 5H), 7.34 (dd, J = 7.6, 1.4 Hz, 1H), 7.55 (dt, J = 8.1,
1.4 Hz, 1H), 7.62 (dt, J = 7.5, 1.30 Hz, 1H), 7.98 (dd, J = 8.1,
1.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): 154.4, 149.6, 140.2,
136.1, 133.5, 133.4, 130.0, 129.3, 127.2, 126.7, 125.0, 124.5,
115.3, 20.6, 13.8, 8.5 ppm.
OH
O
Ph
N
N
montmorillonite k-10
MW
Ph NHNH2
+
R
Ar
R
Ar
1
Compound 4b: Orange oil; IR (KBr, νmax, cm-1): 3052,
2970, 2965, 2920, 1607, 1552, 1487, 1351, 1455, 900, 750;
1H NMR (300 MHz, CDCl3): 1.38 (t, J = 7.5 Hz, 3H), 1.95 (s,
3H), 2.7 (q, J = 7.5 Hz, 2H), 7.20-7.26 (m, 5H), 7.33 (dd, J =
7.5, 1.5 Hz, 1H), 7.58 (dt, J = 8.5, 1.5 Hz, 1H), 7.65 (dt, J =
7.5, 1.30 Hz, 1H), 8.0 (dd, J = 8.5, 1.3 Hz, 1H); 13C NMR (75
4a-e
Scheme-I
All the chemicals were obtained from Merck or Fluka.
All reactions were carried out in a CEM MARS 5TM micro-
wave oven. Silica gel SILG/UV254 plates were used for TLC.

2340 Hatamjafari
Asian J. Chem.
MHz, CDCl3): 156.4, 148.2, 141.2, 135.7, 132.2, 135.5, 132.0,
129.7, 128.0, 127.4, 125.5, 124.5, 116.8, 21.8, 14.2, 8.8 ppm.
Compound 4c: Orange oil; IR (KBr, nmax, cm-1): 3055,
ACKNOWLEDGEMENTS
The author gratefully acknowledged the financial support
from the Research Council of Tonekabon Branch IslamicAzad
University.
1
2972, 2920, 2821, 1590, 1456, 1519, 1340, 750; H NMR
(300 MHz, CDCl3): 1.34 (t, J = 7.2 Hz, 3H), 2.12 (s, 3H), 2.79
(q, J = 7.2 Hz, 2H), 7.20 (dd, J = 8.5, 1.3 Hz, 2H), 7.30-7.38
(m, 3H), 7.40 (d, J = 8.5 Hz, 2H), 8.30 (d, J = 8.5 Hz, 2H); 13C
NMR (75 MHz, CDCl3): 158.0, 148.0, 143.5, 140.8, 135.5,
132.1, 129.2, 128.8, 127.0, 125.9, 120.2, 23.8, 14.5, 8.9 ppm.
Compound 4d: Orange oil; IR (KBr, νmax, cm-1): 3054,
2962, 2855, 1590, 1568, 1490, 1055, 920, 850, 747, 690; 1H
NMR (300 MHz, CDCl3): 1.41 (t, J = 7.5 Hz, 3H), 2.4 (s, 3H),
2.9 (q, J = 7.5 Hz, 2H), 7.3 (dt, J = 7.5, 1.2 Hz, 1H), 7.25-7.35
(m, 8H); 13C NMR (75 MHz, CDCl3): 158.0, 144.1, 142.2,
137.7, 138.8, 135.5, 132.1, 129.5, 128.8, 128.1, 127.1, 126.0,
115.6, 21.1, 13.5, 9.1 ppm.
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1
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13
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Baylis-Hillman adducts were prepared by the reaction of
ethyl vinyl ketone, arylaldehydes17. For synthesis of 1,5-
diarylpyrazole derivatives under microwave, the reaction of
Baylis-Hillman adduct (1), phenylhydrazine hydrochloride in
1,2-dicloroethane was used (Scheme-I). Therefore preparation
of all the 1,5-diarylpyrazoles described in this paper, the
reaction was complete within 5-8 min on solid support under
microwave irradiation in excellent yields (84-90 %) to afford
4a-e (Table-1).
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TABLE-1
THREE-COMPONENT SYNTHESIS
OF SOME 1,5-DIARYLPYRAZOLES
Yields
(%)
Time
(min)
Entry
R
Ar
Product
1
2
3
4
5
-Me
-Et
-Et
-Et
-Et
Phenyl
87
84
86
89
90
5
8
7
7
6
4a
4b
4c
4d
4e
o-Nitrophenyl
p-Nitrophenyl
m-Chlorophenyl
p-Chlorophenyl