A convenient synthesis of 1,5-diarylpyrazoles from Baylis-Hillman adducts using HY-zeolite

Article abstract of DOI:10.1016/j.cclet.2009.07.020

A facile and convenient protocol was developed for the synthesis of 1,5-diarylpyrazoles using Baylis-Hillman adducts in the presence of HY-zeolite as an efficient recyclable heterogeneous catalyst in reasonable reaction times (1.5-2.5 h) and high yields (78-90%).

Full text of DOI:10.1016/j.cclet.2009.07.020

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 5–8
www.elsevier.com/locate/cclet
A convenient synthesis of 1,5-diarylpyrazoles from Baylis-Hillman
adducts using HY-zeolite
*
Mohammad Nikpassand, Manouchehr Mamaghani , Mohammad Ali Zanjanchi,
Nosrat Olah Mahmoodi, Massomeh Mirzaeinejad
Department of Chemistry, Faculty of Sciences, University of Guilan, 41335-1914 Rast, Iran
Received 31 May 2009
Abstract
A facile and convenient protocol was developed for the synthesis of 1,5-diarylpyrazoles using Baylis-Hillman adducts in the
presence of HY-zeolite as an efficient recyclable heterogeneous catalyst in reasonable reaction times (1.5–2.5 h) and high yields
(78–90%).
# 2009 Manouchehr Mamaghani. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: 1,5-Diarylpyrazole; HY-zeolite; Baylis-Hillman; Heterogeneous catalysis
Baylis-Hillman adducts containing chemospecific functional groups in close proximity are versatile building
blocks for the synthesis of several important group of compounds [1–4] which among them are naturally occurring
products such as mycestericin E [5], necic acids [6], terpenoids [7], insect pheromones [8], oxygen- and nitrogen-
containing heterocycles [9–11] and many other biologically active compounds.
An interesting application of Baylis-Hillman adducts has been found in the synthesis of 1,5-diaryl pyrazoles [12].
Aryl pyrazoles are key substructures in a large variety of compounds of important medicinal and pesticidal properties
[13]. Therefore extensive studies have been devoted to the synthesis of these compounds [12]. Arylpyrazoles are
normally prepared from appropriately substituted 1,3-dicarbonyl compounds which suffer from multistep synthesis
and low yields [12,14].
On the other hand, zeolites are used as catalysts for wide range of processes, from simple drying to complicated
catalytic reactions. Acidic zeolites such as HY-zeolite is unique acid catalyst that has become popular over the last two
decades. Zeolite HY contains a framework system of supercages, which are connected by a three-dimensional array of
large diameter channels and this array enables a much easier diffusion of reactants and products [15]. This
heterogeneous catalyst has been used in various chemical transformations [16–20].
Thus the remarkable catalytic activity together with easy availability, operational simplicity of HY-zeolites and our
continued interests for the development of efficient and environmentally friendly procedures for the synthesis of
heterocyclic compounds [21], encouraged us to study the conversion of Baylis-Hillman adducts into 1,5-
diarylpyrazoles in the presence of HY-zeolite.
* Corresponding author.
E-mail addresses: m-chem41@guilan.ac.ir, mchem41@gmail.com (M. Mamaghani).
1001-8417/$ – see front matter # 2009 Manouchehr Mamaghani. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2009.07.020

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M. Nikpassand et al. / Chinese Chemical Letters 21 (2010) 5–8
Scheme 1.
Table 1
Synthesis of 1,5-diarylpyrazoles over HY-zeolite catalyst (2a–i).
Entry
Ar
Ar0
Time (h)
Yield (%)a,b
a
b
c
d
e
f
p-FC6H4
Ph
2.5 (5.5)c
2.0
85 (63)c
87
p-FC6H4
p-MeC6H4
m-BrC6H4
p-BrC6H4
2,4-Cl2C6H3
2-Furyl
Ph
Ph
Ph
Ph
Ph
Ph
Ph
1.75
1.75
2.50
1.75
1.5
83
80
78
86
g
h
i
5-NO2-2-furyl
2-Thienyl
m-ClC6H4
85
1.5
90
1.75
84
a
Isolated yield.
Identified by spectroscopic (IR, 1H NMR, 13C NMR) and elemental analyses.
b
c
Classical reaction was carried out using 1a (0.45 mmol), phenylhydrazine hydrochloride (0.57 mmol) in 1,2-dichloroethane (4 mL) under reflux
condition which provided the pyrazole 2a in 63% yield after 5.5 h.
The Baylis-Hillman adducts (1a–i) were synthesized and converted to the related 1,5-diarylpyrazoles in
ClCH2CH2Cl as solvent, in the presence of HY-zeolite (Si/Al: 2.54) (Scheme 1). The results are summarized in
Table 1.
The characteristic features of the product (2a–i) formation are the appearance of two separate singlets (2.0–
2.62 ppm) for the methyl groups attached to the pyrazole ring. In this protocol the catalytic activity of the catalyst was
remained almost unchanged after fourth reuse of the catalyst which offers very attractive feature to this heterogeneous
catalytic reaction. This reaction was also examined in the absence of the catalyst, by using substrate 1a, which gave the
product (2a) in much longer reaction time and lower yield (Table 1).
Finally we developed a convenient and facile protocol for the synthesis of 1,5-diarylpyrazoles using HY-zeolite, in
low reaction times (1.5–2.5 h) and excellent yields (78–90%).
1. Experimental
Melting points were measured on an Electrothermal 9100 apparatus. IR spectra were determined on a Shimadzo IR-
470 spectrometer. 1H NMR and 13C NMR spectra were recorded on a 500 MHz Bruker DRX-500 in CDCl3 as solvent
and TMS as internal standard. Elemental analyses were done on a Carlo-Erba EA1110CNNO-S analyzer and agreed
with the calculated values. Preparative thin layer chromatography was prepared from Merck Kieselgel 60 H, F254, Art
No. 7730. For column chromatography Merck Kieselgel 60, Art No. 107733 was employed.
A mixture of Baylis-Hillman adduct (1) (0.45 mmol), aryl hydrazine (0.57 mmol) and HY-zeolite (0.1 g) in 1,2-
dichloroethane (4 mL) was refluxed for the required reaction time (Table 1). The mixture 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 (petroleum ether/ethyl acetate: 3/1) to furnish the desired
pyrazole in 78–90% yields (Table 1).
2a: Orange oil; 1H NMR (CDCl3): d 2.06 (s, 3H), 2.37 (s, 3H), 7.03 (m, 2H), 7.17 (m, 5H), 7.29 (m, 2H). 13C NMR
(CDCl3): d 162.8 (d, 1JCF = 245.9 Hz), 152.8, 149.2, 140.5, 131.9 (d, 3JCF = 8.1 Hz), 129.1, 127.5, 127.0, 125.9, 116.1,
115.9 (d, 2JCF = 21.6 Hz), 12.4, 8.9. IR (neat): n 1602, 1506 cmꢀ1 (C C, C N), 1095 cmꢀ1 (C–F). Anal. Calcd. for
C17H15FN2: C, 76.71; H, 5.63; N, 10.52. Found: C, 76.52; H, 5.51; N, 10.31.

M. Nikpassand et al. / Chinese Chemical Letters 21 (2010) 5–8
7
2b: Orange oil; 1H NMR (CDCl3): d 2.06 (s, 3H), 2.35 (s, 3H), 2.36 (s, 3H), 7.01 (m, 4H), 7.13 (d, 2H), 7.44 (d, 2H).
IR (neat): n 1606, 1515 cmꢀ1 (C C, C N), 1161 cmꢀ1 (C–F). Anal. Calcd. for C18H17FN2: C, 77.12; H, 6.11; N, 9.99.
Found: C, 77.20; H, 6.16; N, 9.89.
1
2c: Orange oil; H NMR (CDCl3): d 2.12 (s, 3H), 2.33 (s, 3H), 7.43 (m, 5H), 7.64 (m, 4H). IR (neat): n 1590,
1500 cmꢀ1 (C C, C N), 1070 cmꢀ1 (C–Br). Anal. Calcd. for C17H15BrN2: C, 62.40; H, 4.62; N, 8.56. Found: C,
62.49; H, 4.57; N, 8.63.
2d: Orange oil; 1H NMR (CDCl3): d 2.0 (s, 3H), 2.34 (s, 3H), 7.0 (d, 2H), 7.15 (m, 3H), 7.28 (d, 2H), 7.47 (d, 2H). IR
(neat): n 1600, 1500 cmꢀ1 (C C, C N), 1060 cmꢀ1 (C–Br). Anal. Calcd. for C17H15BrN2: C, 62.40; H, 4.62; N, 8.56.
Found: C, 62.45; H, 4.54; N, 8.59.
2e: Orange oil; 1H NMR (CDCl3): d 2.12 (s, 3H), 2.39 (s, 3H), 7.14 (d, 1H), 7.30 (m, 5H), 7.44 (m, 2H). 13C NMR
(CDCl3): d 146.5, 138.7, 134.5, 132.7, 130.0, 129.8, 129.6, 129.4, 128.7, 128.0, 127.8, 119.3, 113.6, 12.6, 9.3. IR
(neat): n 1595, 1500 cmꢀ1(C C, C N), 1028 cmꢀ1 (C–Cl). Anal. Calcd. for C17H14Cl2N2: C, 64.37; H, 4.45; N, 8.83.
Found: C, 64.43; H, 4.52; N, 8.74.
2f: Purple oil; 1H NMR (CDCl3): d 2.17 (s, 3H), 2.35 (s, 3H), 6.22 (broad, 1H), 6.45 (broad, 1H), 7.24–7.40 (m, 5H),
7.45 (broad, 1H). 13C NMR (CDCl3): d 151.3, 144.8, 143.4, 140.3, 129.8, 128.2, 126.6, 120.6, 115.9, 109.5, 107.8,
12.3, 9.4. IR (neat): n 1595, 1500 cmꢀ1 (C C, C N), 1142 cmꢀ1 (C–O). Anal. Calcd. for C15H14N2O: C, 75.61; H,
5.92; N, 11.76. Found: C, 75.55; H, 5.84; N, 11.83.
2g: Orange oil; 1H NMR (CDCl3): d 2.31 (s, 3H), 2.40 (s, 3H), 7.28 (m, 6H), 7.40 (broad, 1H). IR (neat): n 1600,
1500 cmꢀ1 (C C, C N), 1535 cmꢀ1 (NO2), 1355 cmꢀ1 (NO2), 1070 cmꢀ1 (C–O). Anal. Calcd. for C15H13N3O3: C,
63.60; H, 4.63; N, 14.83. Found: C, 63.72; H, 4.58; N, 14.77.
1
2h: Orange oil; H NMR (CDCl3): d 2.25 (s, 3H), 2.62 (s, 3H), 7.26 (m, 2H), 7.43 (m, 6H). IR (neat): n 1595,
1500 cmꢀ1 (C C, C N). Anal. Calcd. for C15H14N2S: C, 70.83; H, 5.55; N, 11.01. Found: C, 70.77; H, 5.60; N, 10.92.
2i: Orange oil; 1H NMR (CDCl3): d 2.08 (s, 3H), 2.38 (s, 3H), 7.04 (d, 1H), 7.22 (m, 6H), 7.44 (m, 1H), 7.62 (m,
1H). 13C NMR (CDCl3): d 149.3, 140.1, 139.3, 134.6, 133.2, 130.2, 130.1, 128.5, 128.4, 128.3, 127.2, 125.1, 115.5,
12.5, 9.0. IR (neat): n 1600, 1500 cmꢀ1 (C C, C N), 1050 cmꢀ1 (C–Cl). Anal. Calcd. for C17H15ClN2: C, 72.21; H,
5.35; N, 9.91. Found: C, 72.30; H, 5.42; N, 9.80.
Acknowledgments
Financial support from the Research Council of University of Guilan is sincerely acknowledged.
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