Novel crown ether functionalized imidazolium-based acidic ionic liquid catalyzed synthesis of pyrazole derivatives under solvent-free conditions

Article abstract of DOI:10.1007/s11164-014-1782-7

Abstract An innovatively designed novel crown ether functionalized imidazolium-based reusable acidic ionic liquid [crown ether MIm] [HSO₄] has been efficiently implemented for the synthesis of pyrazole derivatives using various substituted enaminones, hydrazine hydrate and phenyl hydrazine under solvent-free conditions. Structural novelty and task efficiency of the catalyst, high yields of desired products, greener approach attributing high atom economy and solvent-free conditions render this protocol suitable to cope with the current demand in contemporary organic chemistry. The inventive idea of utilizing crown ether functionalized ionic liquid as a catalyst was for the first time demonstrated in this protocol.

Full text of DOI:10.1007/s11164-014-1782-7

Res Chem Intermed
DOI 10.1007/s11164-014-1782-7
Novel crown ether functionalized imidazolium-based
acidic ionic liquid catalyzed synthesis of pyrazole
derivatives under solvent-free conditions
•
Dayanand Patil Dattatraya Chandam
•
•
•
•
Abhijeet Mulik Suryabala Jagdale Prasad Patil
Madhukar Deshmukh
Received: 19 April 2014 / Accepted: 1 August 2014
ꢀ Springer Science+Business Media Dordrecht 2014
Abstract An innovatively designed novel crown ether functionalized imidazolium-
based reusable acidic ionic liquid [crown ether MIm] [HSO4] has been efficiently
implemented for the synthesis of pyrazole derivatives using various substituted enami-
nones, hydrazine hydrate and phenyl hydrazine under solvent-free conditions. Structural
novelty and task efficiency of the catalyst, high yields of desired products, greener
approach attributing high atom economy and solvent-free conditions render this protocol
suitable to cope with the current demand in contemporary organic chemistry. The
inventive idea of utilizing crown ether functionalized ionic liquid as a catalyst was for
the first time demonstrated in this protocol.
Keywords Pyrazole ꢀ Crown ether functionalized ionic liquid ꢀ Solvent-free
conditions ꢀ b-enaminone
Introduction
Innovations made in the design of a novel, task-efficient and considerably greener
catalyst along with its implementation in the synthesis of significant human welfare
molecular structures has been a key task for the contemporary research community.
In the last decade, imidazolium based ionic liquids have been found to be a
promising alternative to the hazardous catalysts, organic solvents and reagents in
organic synthesis [1–11]. Ionic liquids, being endowed with the noteworthy aspects
D. Patil ꢀ D. Chandam ꢀ A. Mulik ꢀ S. Jagdale ꢀ M. Deshmukh (&)
Heterocyclic Research Laboratory, Department of Chemistry, Shivaji University,
Kolhapur 416004, MS, India
e-mail: shubhlaxmi111@gmail.com
P. Patil
Department of Agrochemicals and Pest Management, Shivaji University, Kolhapur 416004, MS,
India
123

D. Patil et al.
such as non-volatility, non-flammability, high thermal and chemical stability, large
electrochemical window, high ionic conductivity, relatively low toxicity and
undetectable vapor pressure have attained a crucial platform in the quest of
synthetic methodological augmentation [12, 13]. Consequently, the ILs have been
enabled with attractive applications in the field of material science, electrochem-
istry, gas absorption, nanotechnology and separation technology with an empha-
sized utilization in catalysis and synthetic organic chemistry [14–16].
Pyrazole, a class of two nitrogen-containing five-member heterocycles, has been
observed as an important structural motif owing to its widespread application in
pharmaceutical, chemical and agrochemical sectors [17–19]. Many of the pyrazole
derivatives were materialized as antidepressants and anticonvulsants [20], antitu-
bercular [21], antitumor [22], GABA receptor antagonists and insecticides [23],
anticancer [24] antipyretic [25] anti-inflammatory and antimicrobial agents [26] etc.
Some of the potent pyrazole derivatives are represented in Fig. 1 [27, 28].
There are several methods reported for the synthesis of pyrazole derivatives
which avail hydrazines with 1, 3-dicarbonyl compound, a, b-unsaturated carbonyl
compounds and b-(dimethylamino) enones [29–35]. In spite of the thorough pursuit
lead by the current synthetic researchers, most of the pre-reported methods suffer
from limitations such as use of harmful solvents, tedious products isolation, lower
yield of the desired products and inconvenience in recycling the catalyst.
Thus, with a view to overcome these limitations regarding the synthesis of this
vital moiety and to prove the efficacy of meticulously designed novel crown ether
functionalized imidazolium-based ionic liquid [crown ether MIm] [HSO4], we have
demonstrated an efficient protocol for the synthesis of pyrazole derivatives using the
above novel ionic liquid as a catalyst.
Experimental
General
All reagents were purchased from Thomas Baker and S D Fine-Chem Limited.
Melting points were measured by a Labstar melting apparatus and were uncorrected.
The monitoring of the reaction progress for all reactions was carried out by the thin-
Fig. 1 Representative pyrazole derivatives
123

Novel crown ether functionalized imidazolium
layer chromatography (TLC). Infrared spectra were recorded on a Perkin Elmer
FTIR-1600 spectrophotometer in KBr with absorption in cm-1. 1H NMR, 13C NMR
and 135DEPT spectra were determined on a Bruker Avance (300 and 75 MHz)
spectrometer as DMSO-d6 and CDCl3 solutions using tetramethylsilane (TMS) as
the internal standard. Chemical shifts (d) are expressed in ppm and coupling
constants J are given in Hz. Mass spectra were recorded on a Performa
spectrometer. The UV–VIS absorption spectrum was recorded on a UV 3600
Shimadzu UV–VIS–NIR spectrophotometer with the use of a 1.0 cm quartz cell.
X-ray structure analysis
X-ray diffraction data of compound 3m was collected at T = 296 K on a Bruker
APEXII CCD diffractometer with graphite monochromated Mo Ka (k = 0.71073
˚
A) radiation. Table 5 shows the unit cell parameters and other crystallographic
details. The structure was solved using the direct methods of program SHELXS
2013 and refined anisotropically by full-matrix least-square on F2 was carried out
with the program SHELXL 2013.
Synthesis of ionic liquid [(crown ether MIm] [HSO4]
The crown ether functionalized acidic ionic liquid (monobenzo-15-crown-5)-40-
(1-oxohexyl)-1-methyl-imidazole hydrogen bisulfate [(crown ether MIm] [HSO4]
was synthesized as shown in Scheme 1 in the following steps.
Step 1: Synthesis of benzo-15-crown-5 (5) [39]
A mixture of (30 mmol) of catechol, 50 ml of 1-butanol and (60 mmol) of sodium
hydroxide dissolved in 10 ml of water was stirred for 5 min under nitrogen and
treated with (30 mmol) of 1, 11-dichloro-3, 6, 9-trioxaundecane. The mixture was
refluxed with good agitation for 30 h during which the temperature dropped from
102 to 100 ꢁC. The mixture was acidified with concentrated hydrochloric acid,
cooled to RT, filtered, and the resultant solids were washed with 30 ml of methanol.
The filtrate and the washings were combined and evaporated to dryness in a rotary
vacuum evaporator. The residue was recrystallized in n-heptane to obtained benzo
15-crown-5 (yield = 60 %).
Step 2: Synthesis of 3-(6-bromohexanoyl) benzo-15-crown-5 (6) [40]
Polyphosphoric acid (165 gm) was charged into a 500 ml flask and stirred at 70 ꢁC
in an oil bath for 20 min. Benzo-15-crown-5 (20 mmol) and 6-bromohexanoic acid
(20 mmol) was successively added to the flask. The mixture was maintained at
80 ꢁC for 3–5 h, after which it was poured into ice water and stirred well until
hydrolyze of the polyphosphoric acid. The reaction product in aqueous layer was
further extracted with chloroform for three times. The combined chloroform layers
were washed with saturated Na2CO3 and NaCl solution successively after which the
123

D. Patil et al.
Scheme 1 Synthesis of novel ionic liquid [crown ether MIm] [HSO4]
chloroform was evaporated on rotary evaporator. A yellow product was obtained
and finally it was recrystallized from diethyl ether (yield = 27 %).
Step 3: Synthesis of (monobenzo-15-crown-5)-40-(1-oxohexyl)-1-methyl-imidazole
hydrogen bisulfate (7)
A mixture of 1-methyl imidazole (15 mmol), 3-(6-bromohexanoyl) benzo-15-
crown-5 (15 mmol) and dry acetone (50 ml) was charged into a 250 ml round
bottom flask at RT, after which the reaction temperature was maintained at 50 ꢁC
for 36 h. After completion of the reaction (checked by TLC), the reaction mixture
was cooled and then a stoichiometric amount of sulfuric acid (98 %) was slowly
added at 15–20 ꢁC with vigorous stirring for 20 min. The stirring was continued for
an additional period of 12 h at 50 ꢁC. On evaporating acetone in a rotary evaporator,
a brown colored viscous liquid was observed, which was washed 4–5 times with
acetone (15 ml) to remove non-ionic residue. Finally, it was dried under vacuum at
123

Novel crown ether functionalized imidazolium
Fig. 2 UV–VIS analysis of ionic liquid
50 ꢁC for 1 h to give [(crown ether MIm] [HSO4] as a brownish liquid in 78 %
yield, which was further used as the catalyst.
General procedure for the synthesis of pyrazole derivatives (3a–3p)
In a 50 ml round-bottom flask, substituted enaminones (1 mmol), hydrazine
hydrate (1.3 mmol) or phenyl hydrazine (1 mmol) and [crown ether MIm]
[HSO4] (20 mol%) were charged. The reaction mixture was stirred at 50 ꢁC under
solvent-free conditions for 10–35 min. After completion of reaction (monitored
by TLC), the reaction mixture was extracted with ethyl acetate (2 9 10 ml). The
extracted ethyl acetate was evaporated in a rotary evaporator and the desired
product was isolated from the resultant mass by column chromatography (pet
ether: ethyl acetate, 9.5: 0.5). Finally, the catalyst was recycled and used for the
next run.
Recovery and recyclability of catalyst
The recyclability of our novel catalyst was evaluated with the model reaction
between [3-(dimethylamino) 1-(4-fluorophenyl) prop-2-en-1-one] (1 mmol) and
hydrazine hydrate (1.3 mmol) using 20 mol% of [crown ether MIm] [HSO4] under
solvent-free conditions at 50 ꢁC. After each run, the reaction mixture was extracted
with ethyl acetate (2 9 15 ml) and evaporated in rotary evaporator to give the crude
product, whereas the leftover ionic liquid was washed with diethyl ether
(2 9 10 ml) to remove organic impurities. The catalyst was further dried at
50 ꢁC under reduced pressure and was recovered in excellent yields. The recycled
catalyst was then reused in the subsequent reaction five consecutive times without
any considerable loss of catalytic activity (Fig. 4). The stability of the recycled
123

D. Patil et al.
catalyst after the fifth run was studied by UV–VIS spectrum in ethanol comparison
with fresh UV–VIS spectrum of catalyst (Fig. 2). There was no change observed in
the UV–VIS spectrum of the catalyst, which indicates that it was stable and suitable
for recycling under these conditions.
Characterization data of Ionic liquid and some new representative compounds
(monobenzo-15-crown-5)–40-(1-oxohexyl)–1-methyl-imidazole hydrogen bisulfate
(7)
1
Fresh H NMR (300 MHz, DMSO-d6): d 1.23–1.28 (m, 2H, –CH2), 1.56–1.59 (m,
2H, –CH2), 1.75–1.83 (m, 2H, –CH2), 2.89–2.94 (t, 2H, –CH2), 3.79 (s, 3H,
–NCH3), 3.84 (s, 8H, –OCH2), 3.98–4.02 (t, 2H, –CH2), 4.13–4.18 (m, 4H, –OCH2),
4.26–4.29 (m, 4H, –OCH2), 6.94–6.97 (d, 1H, Ar-H), 7.42–7.49 (m, 2H, Ar-H),
7.67–7.74 (d, 3H, Ar-H), 8.53 (brs, 1H, HSO4); 13C NMR (75 MHz, DMSO-d6): d
23.60, 25.48, 29.63, 36.19, 37.66, 49.10, 64.39, 64.98, 66.03, 68.61, 68.99, 69.27,
69.68, 70.04, 112.75, 117.57, 120.35, 122.67, 123.99, 130.71, 136.86, 143.57,
148.21, 198.86; 135DEPT (75 MHz, DMSO-d6): d 23.74, 25.35, 29.42, 37.67, 49.20,
64.31, 65.02, 66.05, 68.22, 68.44, 69.39, 69.50, 70.10 (–CH2, C), 36.04 (–CH3, C),
112.14, 117.24, 120.04, 122.46, 123.80, 136.26 (–CH, C); ESI–MS (?ve ion) (m/z):
447.3 (M?); ESI–MS (-ve ion) (m/z): 96.9 (M?); Anal. Calcd. for C24H36N2O10S
(544.614): C, 52.93; H, 6.66; N, 5.14. Found: C, 52.87; H, 6.61; N, 5.20.
6,6-dimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one (3 k)
Yellow solid; MP 125–127 ꢁC; IR (KBr): 3431, 3044, 2955, 1655, 1597,
1
1562 cm-1; H NMR (300 MHz, DMSO-d6): d 1.10 (s, 6H, –CH3), 2.34 (s, 2H,
–CH2), 2.49 (s, 2H, –CH2), 8.42 (s, 1H, Ar-H), 13.11 (brs, 1H, NH); 13C NMR
(75 MHz, DMSO-d6): d 28.46, 31.63, 47.42, 50.56, 97.26, 106.94, 151.50, 190.48,
194.90; ESI-MS (m/z): 165.2(M ? H ?); Anal. Calcd. for C9H12N2O (164.204): C,
65.83; H, 7.37; N, 17.06. Found: C, 65.78; H, 7.31; N, 17.11.
1, 5-diphenyl-1H-pyrazole (3 l)
Oil mass; IR (KBr): 3031, 1596, 1500, 1440 cm-1; 1H NMR (300 MHz, CDCl3): d
6.54–6.53 (d, J = 1.8 Hz, 1H, Ar-H), 7.35–7.24 (m, 10H, Ar-H), 7.76–7.75 (d,
J = 1.8 Hz, 1H, Ar-H); 13C NMR (75 MHz, CDCl3): d 107.90, 119.06, 125.23,
127.44, 128.22, 128.78, 128.90, 130.61, 140.12, 140.28, 143.04; ESI–MS (m/z):
221.1(M ? H?); Anal. Calcd. for C15H12N2 (220.269): C, 81.79; H, 5.49; N, 12.72.
Found: C, 81.75; H, 5.43; N, 12.76.
5-(4-fluorophenyl)-1-phenyl-1H-pyrazole (3m)
Brown solid; MP 68–70 ꢁC; IR (KBr): 3066, 2927, 1596, 1549, 1491, 1448 cm-1
;
1H NMR (300 MHz, CDCl3): d 6.51 (s, 1H, Ar-H), 7.10–7.08 (d, J = 6.3 Hz, 2H,
Ar-H), 7.29–7.26 (m, 2H, Ar-H), 7.37–7.32 (m, 3H, Ar-H), 7.44–7.42
123

Novel crown ether functionalized imidazolium
(d, J = 6.3 Hz, 2H, Ar-H), 7.72 (s, 1H, Ar-H); 13C NMR (75 MHz, CDCl3): d
107.83, 115.44, 115.72, 125.24, 126.73, 126.78, 127.57, 128.98, 130.52, 130.63,
139.96, 140.31, 142.00; ESI-MS (m/z): 239.1 (M ?); Anal. Calcd. for C15H11FN2
(238.259): C, 75.62; H, 4.65; N, 11.76. Found: C, 75.57; H, 4.61; N, 11.81.
5-(4-bromophenyl)-1-phenyl-1H-pyrazole (3n)
1
Off white solid; MP 106–110 ꢁC; IR (KBr): 3061, 2924, 1585, 1501 cm-1; H
NMR (300 MHz, CDCl3): d 6.48 (s, 1H, Ar-H), 7.01–7.97 (m, 2H, Ar-H), 7.21–7.18
(m, 2H, Ar-H), 7.36–7.29 (m, 5H, Ar-H), 7.72 (s, 1H, Ar-H); 13C NMR (75 MHz,
CDCl3): d 107.96, 122.52, 125.25, 127.69, 129.05, 129.51, 130.23, 131.71, 139.87,
140.40, 141.81; ESI-MS (m/z): 298.9 (M ?); Anal. Calcd. for C15H11BrN2
(299.165): C, 60.22; H, 3.71; N, 9.36. Found: C, 60.16; H, 3.67; N, 9.41.
5-(4-methylphenyl)-1-phenyl-1H-pyrazole (3o)
1
Oil mass; IR (KBr): 3035 2923, 1598, 1498, 1448 cm-1; H NMR (300 MHz,
CDCl3): d 2.36 (s, 3H, –CH3), 6.51 (s, 1H, Ar-H), 7.16–7.10 (m, 4H, Ar-H),
7.44–7.25 (m, 5H, Ar-H), 7.74 (s, 1H, Ar-H); 13C NMR (75 MHz, CDCl3): d 21.31,
96.20, 107.64, 125.21, 127.24, 127.81, 128.67, 128.80, 129.16, 137.92, 140.25,
142.96; ESI-MS (m/z): 235.1 (M ? H?); Anal. Calcd. for C16H14N2 (234.295): C,
82.02; H, 6.02; N, 11.96. Found: C, 81.98; H, 5.96; N, 12.01.
5-(4-methoxyphenyl)-1-phenyl-1H-pyrazole (3p)
1
Oil mass; IR (KBr): 3136, 2933, 1599, 1498, 1442 cm-1; H NMR (300 MHz,
CDCl3): d 3.79 (s, 3H, –OCH3), 6.44–6.43 (d, J = 1.8 Hz, 1H, Ar-H), 6.83–6.80 (d,
J = 8.7 Hz, 2H, Ar-H), 7.16–7.13 (d, J = 6.9 Hz, 2H, Ar-H), 7.34–7.26 (m, 5H,
Ar-H), 7.69–7.68 (d, J = 1.8 Hz, 1H, Ar-H); 13C NMR (75 MHz, CDCl3): d 55.24,
107.31, 113.70, 113.92, 122.98, 125.22, 127.34, 128.87, 130.04, 130.59, 140.16,
140.19, 142.89, 159.56, 163.50; ESI-MS (m/z): 251.0 (M ? H?); Anal. Calcd. for
C16H14N2O (250.295): C, 76.78; H, 5.64; N, 11.19. Found: C, 76.73; H, 5.58; N,
11.23.
Results and discussion
In continuation of our work in crown ethers [36] and ionic liquids [37, 38], we
decided to design a novel catalyst containing both crown ether and imidazolium
structural motifs. In the same pursuit, we carried out a multistep synthesis using
easily available starting materials catechol and 1, 11-dichloro-3, 6, 9-trioxaunde-
cane (Scheme 1) resulting0 in the formation of the desired novel ionic liquid
(monobenzo-15-crown-5)-4 -(1-oxohexyl)-1-methyl-imidazole hydrogen bisulfate
123

D. Patil et al.
Table 1 Influence of different catalyst and catalyst concentration for the synthesis of pyrazole
derivatives
Entry
Catalyst
Amount (mol%)
Time (min)
Yield (%)a
1
–
–
60
50
40
60
40
15
30
25
45
30
15
10
10
–
2
CH3COOH
20
20
20
20
20
20
20
5
50
60
Trace
45
86
70
68
50
60
85
90
89
3
PSSA
4
Amberlyst-15
5
L-proline
6
[Hmim][HSO4]
7
[Cmim][Cl]
8
[Cmim][Tsa]
9
[Crown ether MIm] [HSO4]
[Crown ether MIm] [HSO4]
[Crown ether MIm] [HSO4]
[Crown ether MIm] [HSO4]
[Crown ether MIm] [HSO4]
10
11
12
13
10
15
20
25
Reaction condition: b-Enaminones [3-(dimethylamino) 1-(4-fluorophenyl) prop-2-en-1-one] (1 mmole)
and hydrazine hydrate (1.3 mmole) at 50 ꢁC
a
Isolated yield
1
which was confirmed by H NMR, 13C NMR, 135DEPT, mass spectroscopy and
elemental analysis.
Initially we carried out the model reaction of [3-(dimethylamino) 1-(4-
fluorophenyl) prop-2-en-1-one] (1 mmol) and hydrazine hydrate (1.3 mmol) at
uncatalyzed condition which afforded negligible yield (Table 1, entry 1). Thus, to
investigate the catalytic activity of the synthesized ionic liquid we carried out the
same reaction using 5 mol% [crown ether MIm] [HSO4] at 50 ꢁC under solvent-free
conditions. As expected, the reaction progressed smoothly affording 50 % yield
(Table 1, entry 9).
Encouraged with the initial success, the same reaction was subjected altering the
catalytic amount from 5 to 20 mol% (Table 1, entries 9–13). The yield of the
desired product was directly proportional to the employed amount of catalyst up to
20 mol% above which no subsequent increase in yield was observed.
The catalytical efficiency of the synthesized catalyst was evaluated by screening
it with various acid catalysts, ionic liquid catalysts and by solvent variations for the
model reaction (Tables 1, 2). The results summarized in Tables 1, 2 clearly suggest
that the best result was obtained using [crown ether MIm] [HSO4] (20 mol%) ionic
liquid as catalyst under solvent-free conditions.
Further studies were initiated for the optimization of temperature conditions to be
employed. The obtained results depicted that 50 ꢁC was the appropriate temperature
in order to afford the desired product in excellent yield with a considerable
abridgement in the reaction time (Table 3).
123

Novel crown ether functionalized imidazolium
Table 2 Effect of solvent
Entry
Solvent
Time (min)
Yield (%)a
1
Water
80
65
75
60
55
80
60
70
90
10
10
Trace
54
2
Ethanol
3
Methanol
48
4
EtOH:H2O (1:1)
Acetonitrile
THF
55
5
75
6
65
7
Acetone
70
8
Ethyl acetate
Toluene
50
9
45
10
11
[Crown ether MIm] [HSO4]
–
89
90
Reaction condition: b-Enaminones [3-(dimethylamino) 1-(4-fluorophenyl) prop-2-en-1-one] (1 mmole),
hydrazine hydrate (1.3 mmole) and [crown ether MIm] [HSO4] 20 mol%
a
Isolated yield
Using these optimized conditions in order to check the scope of generality and
versatility of the protocol, we reacted several substituted enaminones, hydrazine
hydrate and phenyl hydrazine, which afforded good to excellent yields of desired
pyrazole derivatives (Scheme 2; Table 4, entries 1–16).
All the synthesized compounds were confirmed on the basis of their melting
1
points and spectral data (IR, H NMR, 13C NMR, LC–MS and elemental analyses)
Table 3 Effect of temperature
Entry
Temperature (ꢁC)
Time (min)
Yield (%)a
1
2
3
4
RT
40
50
60
60
30
10
10
Trace
65
90
90
Reaction condition: b-Enaminones [3-(dimethylamino) 1-(4-fluorophenyl) prop-2-en-1-one] (1 mmole),
hydrazine hydrate (1.3 mmole) and [crown ether MIm] [HSO4] 20 mol%
a
Isolated yield
Scheme 2 Synthesis of pyrazole derivatives from substituted enaminones
123

D. Patil et al.
Table 4 Synthesis of pyrazole derivatives from various enaminones
123

Novel crown ether functionalized imidazolium
Table 4 continued
Reaction condition: Substituted b-Enaminones (1 mmole), hydrazine hydrate (1.3 mmole) or phenyl
hydrazine (1 mol) and 20 mol% [crown ether MIm] [HSO4] at 50 ꢁC
a
Isolated yield
P
b
% Atom economy = (MW of desired product/ of all reactant) 9 100
compared with those of authentic samples [31]. Furthermore, the molecular
structure of compound 5-(4-fluorophenyl)-1– phenyl-1H-pyrazole (3m) as shown in
(Table 5; Fig. 3) was thoroughly investigated for crystallographic study.
In X-ray single-crystal analysis, the geometry of 3m is triclinic. The geometry
of inter and intra-molecular hydrogen bonds for 3m as shown in Table 6. The
plausible mechanism for the formation of pyrazole has been proposed in
Scheme 3. The enaminone 1 reacted with hydrazine hydrate or phenyl hydrazine
2 to form intermediate 4 with elimination of dimethyl amine. Further the
123

D. Patil et al.
Table 5 Crystal structure and refinement data for 3m
Identification code
3m
Empirical formula
Formula weight
C15H11FN2
238.25
Temperature
296 (2) K
˚
0.71073 A
Wavelength
Crystal system, space group
Unit cell dimensions
Triclinic, P-1
˚
a = 7.9218 (2) A a = 90.0010 (9)ꢁ
˚
b = 7.9810 (2) A b = 100.2787 (10)ꢁ
˚
c = 19.7934 (4) A c = 90.6653 (10)ꢁ
Volume
1231.25 (5) A3
Z, Calculated density
Absorption coefficient
F(000)
21.285 Mg/m3
0.088 mm-1
496
Crystal size
0.320 9 0.250 9 0.100 mm
1.046–24.995ꢁ
-9 B h B 9, -9 B k B 9, -23 B l B 19
18973/4352 [R (int) = 0.0212]
25.242 97.3 %
Theta range for data collection
Limiting indices
Reflections collected/unique
Completeness to theta
Absorption correction
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r(I)]
R indices (all data)
Extinction coefficient
Largest diff. peak and hole
CCDC number
None
Full-matrix least-squares on F2
4352/0/326
1.599
R1 = 0.0347, wR2 = 0.0953
R1 = 0.0466, wR2 = 0.1008
0.019 (2)
0.143 and -0.127 e. A-3
CCDC 996370
intermediate 4 on intramolecular cyclocondensation afforded desired derivative of
pyrazole 3.
Atom economy, recyclability and recovery of the catalyst system with high
efficiency and selectivity are the cornerstones of green synthetic chemistry. Thus,
recyclability of the catalyst was checked and the catalyst was found to be recyclable
without subsequent loss in its activity (Fig. 4). Next, the materiality of the process
was confirmed by the percent atom economy (Fig. 5), which showed that the
resultant product possessed good atom economy. In comparison with the other
employed catalysts for the synthesis of pyrazole derivatives, crown functionalized
ionic liquid showed an excellent activity in the terms of mild conditions, time and
yield (Table 7).
123

Novel crown ether functionalized imidazolium
Fig. 3 ORTEP diagram of compound 3m
Table 6 Hydrogen bonding for 3m
D-H…A
d(D-H)
d(H…A)
d(D…A)
\(DHA)
C(8)-H(8)…F(1)#1
Symmetry transformations used to generate equivalent atoms:
0.93
2.52
3.4345(17)
169.4
#1-x ? 2,-y,-z ? 1
Scheme 3 Plausible mechanism for the formation of pyrazole
123

D. Patil et al.
Fig. 4 Recyclability and reusability of catalyst
Fig. 5 Atom economy of products
Table 7 Comparison of the yield of the synthesis of pyrazole in presence of different systems
Sr. no. Catalyst/solvent Amount Time (min) Yield (%) Ref.
Temp. ꢁC
20 mol% Grinding RT 6–12
1
2
3
4
5
PTSA
60–92
87–95
90–98
78–96
79–92
[31]
–
–
MW
30–120
5–180
20
[32]
Trifluoroethanol
–
RT
[33]
Nano-organocatalyst/H2O
25 mg
MW, 120
[34]
[Crown ether MIm] [HSO4] 20 mol% 50
10–35
Our work
123

Novel crown ether functionalized imidazolium
Conclusions
Here we have demonstrated a meticulously designed novel crown ether function-
alized imidazolium ionic liquid [crown ether MIm] [HSO4] as an eco-friendly and
proficient catalyst to synthesize a series of pyrazole derivatives. To the best of our
knowledge, crown ether functionalized ionic liquid has been implemented for the
first time as a catalyst in an organic transformation. High efficiency, reusability and
recyclability of catalyst, high yields of desired products in considerably shorter
reaction time and environmental benignancy are the noteworthy aspects of this
protocol.
Supplementary Information
Crystallographic data for the structure in this paper have been deposited with the
Cambridge Crystallographic Data Centre as Supplementary Publication No. CCDC
996370. Copies of the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK, (www.ccdc.cam.ac.uk/data_request/cif
or e-mail: deposit@ccdc.cam.ac.Uk).
Acknowledgments The authors are thankful to the Department of Chemistry, Shivaji University,
Kolhapur, for spectral measurements. D.R. Patil is grateful to the UGC New Delhi for awarding him a
Junior Research Fellowship [F. No. 41-211/2012(SR)]. The authors are also grateful to the Department of
Chemistry, IIT Madras, for providing single-crystal analysis data of compound 3m.
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