PEG-SO3H as a mild, efficient and green catalytic system for the synthesis of pyrazole derivatives in aqueous medium

Article abstract of DOI:10.1007/s13738-012-0143-y

A versatile, alternative and environmentally benign strategy for the synthesis of a series of pyrazoles has been successfully performed in water using PEG-SO₃H as an acidic catalyst. The products are obtained in high yield from the one-pot reaction procedure involving dicarbonyl compounds and hydrazines/hydrazides. This new method totally avoids the use of organic acids and toxic or expensive solvents in this reaction. The catalyst is waste-free, easily prepared, and efficiently re-used.

Full text of DOI:10.1007/s13738-012-0143-y

J IRAN CHEM SOC (2013) 10:213–219
DOI 10.1007/s13738-012-0143-y
ORIGINAL PAPER
PEG–SO3H as a mild, efficient and green catalytic system
for the synthesis of pyrazole derivatives in aqueous medium
•
M. A. Nasseri S. A. Alavi B. Zakeri Nasab
•
Received: 29 February 2012 / Accepted: 18 July 2012 / Published online: 9 August 2012
Ó Iranian Chemical Society 2012
Abstract A versatile, alternative and environmentally
benign strategy for the synthesis of a series of pyrazoles
has been successfully performed in water using PEG–
SO3H as an acidic catalyst. The products are obtained in
high yield from the one-pot reaction procedure involving
dicarbonyl compounds and hydrazines/hydrazides. This
new method totally avoids the use of organic acids and
toxic or expensive solvents in this reaction. The catalyst is
waste-free, easily prepared, and efficiently re-used.
tremendous upsurge of interest in various chemical trans-
formations processes by catalysts under heterogeneous
conditions has occurred. These species allow rapid and
simplified procedures and their use has become widespread
in organic synthesis and combinatorial chemistry [6].
Recently, PEG–SO3H has emerged as an efficient bronsted
acid in promoting various organic transformation such as
the synthesis of 3,4-dihydropyrimidones [7], thiocyano-
hydrines [8], triazolo[1,2-a]indazole-triones [9], a-amino-
phosphonates [10], Bis (indolyl) methanes [11], dibenzo
xanthenes [12] and Beckmann rearrangement [13].
Keywords PEG–SO3H ꢀ Pyrazole ꢀ Hydrazine ꢀ
Hydrazide ꢀ Dicarbonyl ꢀ Aqueous medium
Solvents are chemical substances used in huge amounts
for many different applications. In many cases, organic
solvents are chemical substances derived from petrol, and
have a negative impact on the health and the environment.
One of the key areas of green chemistry is the elimination
of solvents in chemical processes or the replacement of
hazardous solvents with environmentally benign solvents.
The use of water as a medium for organic reactions is one
of the latest challenges for modern organic chemists. Water
emerged as a useful alternative solvent for several organic
reactions owing to many of its potential advantages such as
safety, economy and environmental concern [14–19].
Due to the pharmacological properties of pyrazoles,
development of synthetic methods, enabling easy access to
these compounds, is desirable. Therefore, in this paper, we
reportsynthesisofpyrazole derivativesbythecondensationof
dicarbonyl compounds and hydrazines/hydrazides in the
presence of PEG–SO3H under ambient temperature in water.
Introduction
The development of new methodologies for the synthesis
of pyrazoles is a subject of continuous interest to synthetic
organic/medicinal chemists as pyrazole and their deriva-
tives have versatile biological activities [1]. These com-
pounds are known to exhibit a wide spectrum of
therapeutic and pharmacological properties such as anti-
tumor cyclin-dependent kinase (CDK) inhibitors, mono-
amine oxidase-B (MAO-B) inhibitor, antiinflammatory
agents and a typical antipsychotics property [2–4].
Solid acids can replace traditional mineral acids as safer
alternatives. In recent years, the use of solid acidic catalysts
has offered important advantages in organic synthesis, e.g.,
operational simplicity, environmental compatibility, non-
toxic, reusability, low cost, and ease of isolation [5]. A
Experimental
M. A. Nasseri (&) ꢀ S. A. Alavi ꢀ B. Zakeri Nasab
Department of Chemistry, College of Sciences,
Birjand University, 97175-615 Birjand, Iran
Materials and apparatus: dicarbonyl compounds and
hydrazines/hydrazides were purchased from Merck
e-mail: malinasseri@yahoo.com; manaseri@birjand.ac.ir
123

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J IRAN CHEM SOC (2013) 10:213–219
Chemical Companies. Purity determinations of the prod-
ucts were accomplished by TLC on silica-gel polygram
SILG/UV 254 plates. Melting points were determined in
electrothermal 9100 system open capillaries and were
uncorrected. IR spectra were taken on a Perkin Elmer 781
spectrometer in KBr pellets and reported in cm-1. NMR
spectra were measured on a Bruker DPX 250 MHz spec-
trometer in DMSO-d6 with chemical shift given in ppm
relative to TMS as internal standard.
Pentane-2,4-dionebis[(2,4-dinitrophenyl)hydrazone]
1
(6a): mp: 179–180 °C (Lit [20]. 179–180 °C) H NMR
(250 MHz, CDCl3) d 2.17 (s, 6H, CH3), 3.58 (s, 2H, CH2),
7.94 (d, 2H, J = 7 Hz, Ar), 8.32 (m, 2H, Ar), 9.14 (d, 2H,
J = 3 Hz, Ar), 11.15 (s, 2H, NH). 13C NMR (62.9 MHz,
CDCl3) d 16.1, 42.7, 116.3, 123.5, 129.7, 130.2, 138.2,
145.2, 153.0. mmax (kBr) 3,315, 3,100, 2,985, 1,615, 1,590,
1,510, 1,495, 1,420, 1,322, 1,312, 1,219, 1,133, 1,093,
1,061, 924, 829, 742. MS (m/z, %): 460 (M?,1), 374 (2),
368 (1), 297 (4), 167 (11), 149 (39), 113 (6), 70 (37), 57
(54), 43 (100). Anal. Calcd. For C17H16N8O8 (%): C,
44.35; H, 3.50; N, 24.34. Found: C, 44.21; H, 3.39; N,
25.07.
Preparation of PEG–SO3H
PEG–SO3H was synthesized according to the literature
procedure [9]. To a magnetically stirred mixture of
6.00 g (1 mmol) of poly(ethylene glycol) (PEG) in 10 ml
of dichloromethane, 0.67 ml of chlorosulfonic acid
(10 mmol) was added dropwise at 0 °C during 1 h. HCl
gas was removed from the reaction vessel immediately
and the mixture was stirred for 12 h. The mixture was
filtered and washed with 20 ml of diethyl ether and
dried at room temperature to afford 5.10 g of PEG–SO3H
as a white powder. The number of H? sites on the PEG–
SO3H was determined by acid–base titration to be
0.5 mmol/g.
Ethyl-3-[(2,4-dinitrophenyl)hydrazono]butanoate
(7b): mp: 88–89 °C(Lit [20]. 88–90 °C) 1H NMR
(250 MHz, CDCl3) d 1.28 (t, 3H, J = 10 Hz, CH3), 2.17
(s, 3H, CH3), 3.48 (s, 2H, CH2), 4.24 (q, 2H, J = 10 Hz,
CH2), 7.9 (d, 1H, J = 8 Hz, Ar), 8.28 (m, 1H, Ar), 9.10 (d,
1H, J = 3 Hz, Ar), 11.10 (s, 1H, NH). 13C NMR
(62.9 MHz, CDCl3) d 14.2, 16.2, 44. 8, 61.5, 116.6, 123.4,
129.2, 130.0, 138.3, 145.0, 150.8, 169.3. mmax (kBr) 3,312,
3,100, 2,985, 1,727, 1,620, 1,596, 1,517, 1,425, 1,365,
1,340, 1,313, 1,278, 1,255, 1,209, 1,180, 1,100, 1,086,
1,030, 920, 837, 743. MS (m/z, %): 310 (M?, 5), 279 (2),
264 (3), 237 (5), 219 (12), 196 (7), 173 (5.6), 167 (8), 149
(34), 131 (14), 115 (22), 103 (25), 90 (29), 76 (46), 57 (44),
41 (100). Anal. Calcd. For C12H14N4O6 (%): C, 46.45; H,
4.55; N, 18.06. Found: C, 45.96; H, 4.39; N, 18.37.
General procedure for the preparation of pyrazole
derivatives
To a mixture of dicarbonyl compounds (1.0 mmol) and
hydrazines/hydrazides (1.0 mmol), PEG–SO3H (0.1 g) in
H2O (2 ml) was added. The mixture was stirred at rt for the
given time (Tables 3, 4). The progress of the reaction was
monitored by TLC. After completion of the reaction,
the product was extracted with ethyl acetate (2 9 10 ml).
The organic layer was dried (Na2SO4), evaporated and the
crude product was purified by flash column chromatogra-
phy (ethyl acetate/n-hexane, 1:20) to provide the pure
product. All products were identified by comparison of
analytical data (IR, NMR, MS) with those reported for
authentic samples [20].
3-methyl-1H-pyrazol-5-ol(5a):
mp:
220–222 °C
(220–224 °C, CAS No. 108-26-9) 1H NMR (250 MHz,
DMSO) d 2.07 (s, 3H, CH3), 5.2 (s, 1H), 10.3 (br, 2H, NH
and OH). 13C NMR (62.9 MHz, DMSO) d 11.5, 89.4,
140.2, 161.6. mmax (kBr) 2,200–3,400, 1,620, 1,564, 1,457,
1,250, 1,195, 985, 765. MS (m/z, %): 99 (M ?1, 5), 98
(M?, 100), 81 (1), 69 (15), 67 (16), 56 (12), 40 (30). Anal.
Calcd. For C4H6N2O (%): C, 48.97; H, 6.16; N, 28.56.
Found: C, 49.09; H, 6.03; N, 28.38.
5-methyl-2-phenyl-2,4-dihydro-3H-pyrazole-3-one
1
(4a): mp: 127–128.5 °C(Lit [21]. 127–129 °C) H NMR
(250 MHz, CDCl3) d 2.19 (s, 3H, CH3), 3.42 (s, 2H, CH2),
7.18 (m, 1H, Ph) 7.37 (m, 2H, Ph) 7.78 (m, 2H, Ph). 13C
NMR (62.9 MHz, CDCl3) d 17.1, 43.1, 118.9, 125.1,
128.8, 138.0, 156.4, 170.6. mmax (kBr) 3,050, 2,920, 1,750,
1,585, 1,490, 1,440, 1,380, 1,350, 1,170, 1,140, 1,030, 910,
810, 760, 750, 680, 640. MS (m/z, %): 175 (M ? 1, 4.8),
174 (M?, 50), 149 (4), 145 (6), 142 (2), 132 (7), 105 (26),
91 (58), 77 (100), 63 (41), 50 (65), 41 (43). Anal. Calcd.
For C10H10N2O (%): C, 68.95; H, 5.79; N, 16.08. Found:
C, 68.42; H, 5.42; N, 15.88.
Selected spectral data
3,5-dimethyl-1-phenyl-1H-pyrazole: oil 1H NMR
(250 MHz, CDCl3) d 2.29 (s, 6H, 2CH3), 5.99 (s, 1H, CH),
7.34 (m, 5H, ph) 13C NMR (62.9 MHz, CDCl3) d 12.4,
13.5, 106.9, 124.7, 127.2, 129.0, 139.4, 139.9, 148.9. mmax
(kBr) 3,055, 2,981, 2,959, 2,910, 2,861, 1,597, 1,546,
1,492, 1,420, 1,381, 1,366, 1,131, 1,072, 1,020, 977, 911,
779, 755, 690. MS (m/z, %): 172 (M?, 38), 130 (20), 118
(18), 105 (28), 91 (18), 77 (100), 65 (25), 56 (18), 51 (48),
43 (67). Anal. Calcd. For C11H12N2 (%): C, 76.71; H, 7.02;
N, 16.27. Found: C, 76.58; H, 7.15; N, 16.32.
Ethyl-3-(acetylhydrazono)butanoate(8d): mp: 88–90 °C
(Lit [22] 89 °C) 1HNMR (250 MHz, CDCl3) d 1.24 (t,
J = 7.3 Hz, 3H, CH3), 1.92 (s, 3H, CH3), 2.20 (s, 3H,
CH3), 3.26 (s, 2H, CH2), 4.13 (q, 2H, J = 7.3 Hz, CH2),
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J IRAN CHEM SOC (2013) 10:213–219
215
9.33 (s, 1H, NH). 13C NMR (62.9 MHz, CDCl3) d 13.2,
17.9. 20.1, 41.8, 60.5, 163.9, 165.7, 173.5. mmax (kBr)
3,190, 2,980, 2,930, 1,725, 1,680, 1,460, 1,380, 1,330,
1,260, 1,190, 1,120, 1,030, 870, 730, 620. MS (m/z, %):
187 (M ? 1, 1), 186 (M?,10), 171 (2), 144 (9), 113 (3), 98
(100), 70 (28), 57 (11.0), 54 (11), 42 (26). Anal. Calcd. For
C8H14N2O3 (%): C, 51.60; H, 7.58; N, 15.04. Found: C,
51.64; H, 7.55; N, 15.09.
Table 1 The effect of different amounts of PEG–SO3H as a catalyst
and various temperatures in the reaction of pentane-2,4-dione
(1 mmol) and phenyl hydrazine (1 mmol) at 5 min in the present of
H2O
Entry
Catalyst (g)
Yield
rt
60 °C
80 °C
1
2
3
4
5
6
0
8
78
98
94
82
60
15
77
88
70
66
40
12
65
65
60
58
33
0.05
0.1
1-(2-furoyl)-3,5-dimethyl-1H-pyrazole: mp:105–106 °C.
1H NMR (400 MHz, CDCL3) d 2.10 (s, 3H, CH3), 2.58 (s,
3H, CH3), 5.83 (s, 1H, CH), 6.39 (m, 1H, CH), 7.52 (d,1H,
J = 3 Hz, CH), 7.74 (d, 1H, J = 3 Hz, CH). 13C NMR
(100 MHz, CDCl3) d 12.6, 15.1, 106.6, 113.2, 120.5,
135.2, 144.9, 145.6, 154.3, 158.3. MS (m/z, %): 191
(M ? 1, 8.7), 190 (M?, 33.5), 161 (100), 133 (28.9), 108
(24.5), 94 (54). mmax (kBr) 3,125, 3,100, 2,990, 2,930,
1,680, 1,585, 1,565, 1,460, 1,375, 1,350, 1,275, 1,025, 950,
875. Anal. Calcd. For C10H10N2O2 (%): C, 63.15; H, 5.30;
N, 14.73. Found: C, 63.45; H, 5.26; N, 15.18.
0.15
0.2
0.25
condition gives pyrazole in a rather low yield of 8–15 %
(Table 1, entry 1).
This reaction was also carried out in various solvents,
with PEG–SO3H (0.1 g or 0.05 mmol H?) as a catalyst, at
room temperature for 5 min. The reaction proceeded per-
fectly in polar solvents (Table 2, entries 1, 2, 3, 7, 10, 11),
but the yields decreased when the reaction was carried out
in non-polar solvents (Table 2, entries 8, 9, 12). It was very
surprising that the reaction proceeded in excellent yields
(98 %) in aqueous medium (Table 2, entry 1).
Results and discussion
PEG–SO3H was prepared from polyethyleneglycol (PEG)
and chloro sulfonic acid using a simple and convenient
procedure. This polymeric catalyst was used as an efficient
bronsted acid catalyst for different organic functional
group transformations either as reagent or as catalyst under
heterogeneous and homogenous conditions (Scheme 1).
Herein, we focused on the synthesis of a series of pyr-
azoles analogs using various dicarbonyl and hydrazines/
hydrazides. At the onset of this work, the reaction of
pentane-2,4-dione (1 mmol) and phenyl hydrazine
(1 mmol) as the model substrates was studied (Scheme 2).
In preliminary experiment, we changed temperature and
the amountof catalyst. The results are summarized in Table 1.
Consequently, among the tested temperature and the amount
of catalyst, the condensation of pentane-2,4-dione (1 mmol)
and phenylhydrazine (1 mmol) was bestcatalyzed by0.1 g of
PEG–SO3H at room temperature. Control experiments indi-
cate that in the absence of the catalyst, the reaction at the same
To further explore the scope and limitation of this protocol
under the optimized conditions (5 mol % catalyst in H2O at rt),
particularly in regard to library construction, was evaluated
using various hydrazines/hydrazides, and diketone com-
pounds. The results are summarized in Table 3. In all cases, the
reaction proceeded readily at rt to afford the corresponding
pyrazoles in good to excellent yields (75–98 %) in very short
reaction times (5–60 min). When pentane-2,4-dione was
employed, the reaction proceeded readily and the desired
Table 2 The effect of various solvent in the reaction pentane-2,4-
dione (1 mmol) and phenyl hydrazine (1 mmol), catalyst (0.05 or
0.1 g), solvent (2 ml), stirred at room temperature for 5 min
Entry
Solvent
Yield %
Entry
Solvent
Yield %
1
2
3
4
5
6
7
H2O
98
78
60
40
40
20
75
8
9
n-Hexane
CHCl3
Trace
Trace
70
EtOH
CH3CN
THF
10
11
12
13
14
DMSO
MeOH
85
CH2Cl2
CH2Cl2
Toluene
EtOAC
Dioxane
DMF
Trace
64
PEG-
OH
ClSO3H
PEG-
OSO3H
r.t
Solvent free
76
Scheme 1 Preparation of PEG–SO3H
Scheme 2 Synthesis of
pyrazole derivatives catalyzed
by PEG–SO3H
Ph
O
O
H
N
N
N
PEG-SO3H
H2O, r.t
Ph
NH2
Me
Me
Me
Me
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J IRAN CHEM SOC (2013) 10:213–219
Table 3 Preparation of
pyrazole derivatives catalyzed
by PEG–SO3H
R3
O
O
N
N
O
H
PEG-SO3H
H2O, r.t
N
R1
R3
NH2
R1
R2
R2
Entry
1
R1
R2
R3
Time(min)
5
Yield(%)a
98
Me
Me
2
Me
Me
5
89
87
O
O
O
3
4
5
Me
Me
Me
Me
Me
Me
10
Me
H
5
5
95
90
Cl
5
88
6
7
8
Me
Ph
Ph
Me
S
O
O
CF3
CF3
15
35
76
85
O
O
9
Ph
CF3
45
85
Me
Cl
10
11
Ph
Ph
CF3
Ph
15
30
75
83
12
13
Ph
Ph
Ph
Ph
50
60
87
78
O
Reaction conditions:
O
hydrazines/hydrazides
(1 mmol), diketone (1 mmol),
PEG–SO3H (0.05 mmol H?),
H2O (2 ml), stirred at room
temperature
O
Me
a
Isolated yields
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J IRAN CHEM SOC (2013) 10:213–219
217
Table 4 The reaction of b-ketoester with hydrazines or hydrazides
Entry
Hydrazines/hydrazides
R1
R2
Product
Time (min)
Yield (%)a,b
1
Phenyl hydrazine
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
OMe
OEt
4a
4a
4b
4b
5a
5a
6a
7a
7b
8a
8b
8c
8d
8e
8f
25
15
20
10
15
10
35
60
50
45
45
35
40
25
35
79
87
80
88
85
88
79c
72
78
76
72
80
81
78
77
2
Phenyl hydrazine
3
4-Chlorophenylhydrazine
4-Chlorophenylhydrazine
Hydrazine
OMe
OEt
4
5
OMe
OEt
6
Hydrazine
7
2,4-Dinitrophenylhydrazine
2,4-Dinitrophenylhydrazine
2,4-Dinitrophenylhydrazine
2-Furancarboxylic acidhydrazide
Acetohydrazide
Me
8
OMe
OEt
9
10
11
12
13
14
15
a
OMe
OMe
OEt
2-Furancarboxylic acidhydrazide
Acetohydrazide
OEt
2-Thiophencarboxylic acidhydrazide
2-Thiophencarboxylic acidhydrazide
OEt
OMe
Reaction conditions: nucleophile (1 mmol), b-ketoester (1 mmol), PEG–SO3H (0.05 mmol H?), water (2 ml)
b
c
The yield refers to pure isolated product
Nucleophile 2 mmol
pyrazole was afforded in high yields (Table 3, entries 1–6). It is
b-Ketoester has been used with similar success to provide
the corresponding pyrazole derivatives which are also much
interest with respect to their biological activities (Table 4). As
shown in Tables 3 and 4, it was found that this method works
with a wide variety of substrates. A series of different
substituted diketones, including electron-withdrawing or
electron-donating groups, and different substituted b-keto-
esters were used in this reaction. Additionally, the reaction
with various hydrazines or hydrazides also proceeded.
delighted that some less reactive carbon electrophiles such as
1,3-diphenyl propane-1,3-dione could serve as good substrates
in this reaction (Table 3, entries 11–13), however, the reaction
time of 1,3-diphenyl propane-1,3-dione was longer than
those of acethylaceton, which is probably due to low reactivity
of carbonyl groups. In the case of the reaction between
4,4,4-trifluoro-1-phenylbutane-1,3-dione and phenyhydrazine,
low activity of benzoyl group caused that the second attack for
ring closure and pyrazole ring formation needs a longer time.
Moreover, the reaction yield is decreased to 76 % (Table 3,
entries 7–10). Also, it was found that both hydrazines and
hydrazides could be used. The reaction time of hydrazides and
1,3-dicarbonyl compounds was longer than those of hydra-
zines. This behavior could result from the low reactivity of
hydrazides.
It is noteworthy that phenylhydrazine reacted with
b-ketoester to form the product 4a containing carbonyl
group on ring systems (Scheme 3; Table 4, entry 1–2). But
it is interesting that when hydrazine and b-ketoester were
used as the substrates, the reaction failed to afford the
expected product. In this case, another type of pyrazole
analog, 3-methyl-1H-pyrazole-5-ol (5a), was obtained in
Scheme 3 Comparison of
hydrazine/phenylhydrazine in
the reaction with b-ketoester
R1
R =
Me
, R
O
=O
Et,
OM
e
1
2
N
N
R3=Ph
O
O
R3
H
N
R1
4
R2
R3
NH2
R3=H
R1
OH
R =
Me
, R
=O
Et,
OM
e
1
2
N
N
R3
5
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J IRAN CHEM SOC (2013) 10:213–219
R1
Scheme 4 Condensation of
2,4-dinitrophenylhydrazine with
diketones or b-ketoesters
R2
O2N
NO2
N
N
N
N
R1=R2=Me
H
H
NO2
O2N
O
O
6
O2N
NHNH2
R1
R2
R1
R2
NO2
O2N
N
O
N
H
R =
Me
, R
=OE
t, O
M
e
1
2
NO2
7
Scheme 5 Reaction of methyl/
furyl hydrazide with dicarbonyl
compounds
R2
O
R =
M
e, R
=M
e
N
1
2
N
R3
O
O
R1
H
R3
N
R3=Me, Furyl
R1
NH2
R2
R1
R2
O
O
N
O
R
=M
e, R
=OE
t, O
Me
1
2
N
R3
H
8
85 and 88 % isolated yield (Scheme 3; Table 4, entry 5,6).
This result clearly showed that the groups on nitrogen
could lead to different structures of pyrazole.
could be recovered by evaporation of water and washing
with diethyl ether. The recycled catalyst could subject to a
second or even another reaction. In the model reaction, the
results of the first experiment and the subsequent were
almost consistent in yield after six runs (97 %, 94 %,
92 %, 89 %, 87 %, 82 %, Fig. 1).
Following this procedure, we tested 2,4-dinitrophenyl-
hydrazine in the reaction in order to obtain the same pyr-
azole but without different substituents on the N-atom.
Surprisingly, the products were not the desired pyrazole
(the expected products of the reaction of acethylaceton and
phenylhydrazine are shown in Scheme 2). We have found
that the condensation of 2,4-dinitrophenylhydrazine with
diketone or b-ketoester leads to the formation of 6 and 7
compounds, respectively (Scheme 4; Table 4, entry 7–9).
The low reactivity of 2,4-dinitrophenylhydrazine contain-
ing electron-withdrawing groups (NO2) can be attributed to
their relatively weak nucleophilicity and, therefore,
decreased activity in this reaction. The use of stoichiome-
tric quantities (1:1) of 2,4-dinitrophenylhydrazine and
diketone gave product 6 in 33 % yield relative to the
diketone. Treatment 1 eq. of diketone with 2 eq. of 2,4-
dinitrophenylhydrazine improved the yield to 79 %.
When hydrazides were employed with b-ketoester, the
reaction did not give any pyrazole-products and the imine
adducts 8a–8f was only isolated product (Scheme 5;
Table 4, entry 10–15). Nevertheless, diketones led to the
desired pyrazole in an excellent yield (Scheme 5; Table 3,
entry 2,3 and 6).
Conclusion
In conclusion, efficient synthesis of novel pyrazole deriv-
atives has been achieved by a one-pot coupling reaction of
It is noteworthy to mention that the catalyst is recyclable
and could be reused without significant loss of activity. It
Fig. 1 Reuses performance of the catalysts
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219
7. X. Wang, Z. Quan, F. Wang, M. Wang, Z. Zhang, Z. Li, Synth.
Commun. 36, 451 (2006)
8. A.R. Kiasat, M.F. Mehrjardi, Catal. Commun. 9, 1497 (2008)
9. A. Hasaninejad, A. Zare, M. Shekouhy, Tetrahedron 67, 390
(2011)
10. C.B. Reddy, K.S. Kumar, M.A. Kumar, M.V. Narayana Reddy,
B.S. Krishna, M. Naveen, M.K. Arunasree, C.S. Reddy, C.N.
Raju, C.D. Reddy, Eur. J. Med. Chem. 47, 553 (2012)
11. A. Hasaninejad, M. Shekouhy, A. Zare, S.M.S. Hoseini Ghattali,
N. Golzar, J. Iran. Chem. Soc. 8, 411 (2011)
12. P. Davinder, N. Mahendra, Catal. Sci. Technol. 2, 93 (2012)
13. X.C. Wang, L. Li, Z.J. Quan, H.P. Gong, H.L. Ye, X.F. Cao,
Chin. Chem. Lett. 20, 651 (2009)
dicarbonyl compounds and hydrazines/hydrazides. The
products were prepared in water, an excellent solvent in
terms of environmental impact and with reduced waste
production. Simple reaction procedures, inexpensive cata-
lysts and single product formation make this an attractive
protocol over the existing procedures.
Acknowledgments We gratefully acknowledge the support of this
work by the Birjand University Research Council.
14. C.J. Li, Chem. Rev. 105, 3095 (2005)
15. C.J. Li, T.H. Chan, Organic Reactions in Aqueous Media (Wiley,
New York, 1997)
16. F. Bazi, H. El Badaoui, S. Tamani, S. Sokori, A. Solhy, D.J.
Macquarrie, S. Sebti, Appl. Catal. A. General 301, 211 (2006)
17. A.K. Chakraborti, S. Rudrawar, K.B. Jadhav, G. Kaur, S.V.
Chankeshwara, Green Chem. 9, 1335 (2007)
References
1. A.R. Katritzky, C.W. Rees, E.F. Scriven, Comprehensive Het-
erocyclic Chemistry (Pergamon Press, Oxford, 1996) p. 5
2. R. Lin, G. Chiu, Y. Yu, P.J. Connolly, S. Li, Y. Lu, M. Adams,
A.R. Fuentes-Pesquera, S.L. Emanuel, L.M. Greenberger, Bioorg.
Med. Chem. Lett. 17, 4557 (2007)
18. G.L. Khatik, R. kumar, A. K. Chakraborti. Org. Lett. 8, 2433 (2006)
19. S.V. Chankeshwara, A.K. Chakraborti, Org. Lett. 8, 3259 (2006)
20. Z. Wang, H. Qin, Green Chem. 6, 90 (2004)
21. Y.Y. Hung, H.C. Lin, K.M. Cheng, W.N. Su, K.C. Sung, T.P.
Lin, J.J. Huang, S.K. Lin, F.F. Wong, Tetrahedron 65, 9592
(2009)
3. N. Gokhan-Kelekci,S. Yabanoglu,E.Kupeli, U. Salgin,O.Ozgen,G.
Ucar, E. Yesilada, E. Kendi, A.A. Yesilada, A.A. Bilgin, Bioorg.
Med. Chem. 15, 5775 (2007)
4. M. Barcelo, E. Ravina, C.F. Masaguer, E. Domı0nguez, F.M.
Areias, J. Brea, M.I. Loza, Bioorg. Med. Chem. Lett. 17, 4873
(2007)
22. V.G. Yusupov, S.D. Nasirdinov, S.I. Yakimovich, N.A. Parpiev,
J. Gen. Chem. USSR. 50, 2547 (1980)
5. S. Ko, C.F. Yao, Tetrahedron Lett. 47, 8827 (2006)
6. C.G. Knight, T. Stephens, Biochem. J. 683 (1989)
123