Catalyst application of ZnO nanostructures in solvent free synthesis of polysubstituted pyrroles

Article abstract of DOI:10.1016/j.molliq.2013.12.018

A simple, rapid, efficient, and environmentally benign procedure for synthesis of polysubstituted pyrroles has been achieved by the three-component reaction of amines, phenacyl bromide and dialkyl acetylenedicarboxylates under solvent free conditions using nano structures of ZnO as catalyst. Different morphologies such as nanorods and nanosheets of catalysis have been synthesized by simple reflux method using sodium dodecylsulfate (SDS) and applied in this reaction. Nanorod ZnO catalyst exhibited a significant enhancement in the yield of the desired product. The catalyst exhibited remarkable reusable activity.

Full text of DOI:10.1016/j.molliq.2013.12.018

Journal of Molecular Liquids 193 (2014) 116–122
Contents lists available at ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Catalyst application of ZnO nanostructures in solvent free synthesis of
polysubstituted pyrroles
b
Maryam Sabbaghan a, , Azam Ghalaei
⁎
a
Chemistry Department, Faculty of Sciences, Shahid Rajaee Teacher Training University, P O Box 16785–163, Tehran, Iran
Chemistry Department, Science and Research Branch, Islamic Azad University, Khouzestan, Iran
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 October 2013
Received in revised form 19 November 2013
Accepted 14 December 2013
Available online 27 December 2013
A simple, rapid, efficient, and environmentally benign procedure for synthesis of polysubstituted pyrroles has been
achieved by the three-component reaction of amines, phenacyl bromide and dialkyl acetylenedicarboxylates under
solvent free conditions using nano structures of ZnO as catalyst. Different morphologies such as nanorods and nano-
sheets of catalysis have been synthesized by simple reflux method using sodium dodecylsulfate (SDS) and applied in
this reaction. Nanorod ZnO catalyst exhibited a significant enhancement in the yield of the desired product. The
catalyst exhibited remarkable reusable activity.
Keywords:
Nano ZnO
© 2013 Elsevier B.V. All rights reserved.
Amine
Activated acetylene
Phenacyl bromide
Pyrrole synthesis
Green synthesis
1. Introduction
Herein we disclose a general, rapid, high yielding and green synthet-
ic protocol for wide variety three-substituted pyrroles from amines,
Pyrroles represent an important class of heterocyclic compounds
[1–4]. They are commonly found as structural motifs in bio-active mol-
ecules such as porphyrins, alkaloids and co-enzymes [5]. Pyrrole deriv-
atives have attracted particular attention in drug discovery due to their
various pharmacological properties [6–10]. For example, anticancer
drug candidate tallimustine and blockbuster cholesterol lowering drug
atorvastatin (Lipitor) belong to this class. In view of their tremendous
application in various research fields including biological science and
medicinal chemistry, there is a continuing interest in developing versa-
tile synthetic routes [11,12].
Various methodologies have been developed for polysubstituted
pyrrole synthesis [13–15]. However there are disadvantages associated
with some of the reported procedures such as the requirement of sol-
vent, long reaction times, sensitive catalyst, etc.
In recent years, there has been an enhanced interest in catalysis by
nano materials. These materials exhibit better catalytic activity compared
to their bulk sized counterparts [16,17]. Zinc oxide nanostructure is a non-
hygroscopic, inexpensive and non-toxic material, which was used as a cat-
alyst in organic reactions [18–22]. On the other hand, the elimination of
volatile organic solvents in organic syntheses is the most important goal
in green chemistry [23–25]. Solvent-free organic reactions make synthe-
ses simpler, save energy, and prevent solvent wastes, hazards and toxicity.
phenacyl bromide and dialkyl acetylenedicarboxylates by ZnO nano-
structures with different morphologies.
2. Experimental
2.1. Material and instrument
All chemicals were obtained from Fluka or Merck and were used
without further purification. Samples of nanoparticle, nanosheet and
nanorod ZnO were synthesized in the labratory. The morphology of
nanostructure ZnO was determined by using scanning electron micros-
copy (SEM) of a Holland Philips XL30 microscope. X-ray diffraction
(XRD) analysis was carried out at room temperature using a Holland
Philips Xpert X-ray powder diffractometer with Cu Ka radiation
(λ = 0.15406 nm), over the 2θ collection range of 20–80°. Average
crystallite sizes of products were calculated using Scherrer's formula:
D = 0.9λ/β cos θ [26], where D is the diameter of the nanoparticles, λ
(Cu Kα) =1.5406 Å and β is the full-width at half-maximum of the dif-
fraction lines. In order to determine the structure of organic com-
pounds: The IR spectra were recorded using a Shimadzu IR-460
spectrometer. 1H NMR and 13C NMR spectra were measured on Bruker
DRX-250 AVANCE instrument in CDCl3 at 250 and 62.5 MHz, respec-
tively δ in ppm, J in Hz. Mass spectra were obtained on a Finnigan
MAT-8430 at 70 eV. Elemental analyses (C, H, N) were performed
with a Heraeus CHN-O-Rapid analyzer.
⁎
Corresponding author at. Chemistry Department, Faculty of Sciences, Shahid Rajaee
Teacher Training University, P O Box 16785-163, Lavizan, Tehran, Iran.
E-mail address: sabbaghan@srttu.edu (M. Sabbaghan).
0167-7322/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molliq.2013.12.018

M. Sabbaghan, A. Ghalaei / Journal of Molecular Liquids 193 (2014) 116–122
117
Table 1
The corresponding experimental conditions and morphologies of samples.
Entry Zn(OAc)2.2H2O (mol) NaOH (mol) Water (mL) SDS (mol) Morphology
1
2
3
0.003
0.009
0.003
0.01
0.03
0.01
75
75
75
–
nanoparticle
nanosheet
nanorod
0.015
0.005
NR-ZnO
NS-ZnO
2.2. General procedure for synthesis of catalysts
2.2.1. General procedure for the preparation of nanoparticle ZnO (NP-ZnO)
Sodium hydroxide (0.44 g) was disolved in distilled water (75 mL)
at room temprature, zinc acetate dihydrate (0.6 g) was added to the
mixture and the solution was refluxed for 1.5 h at 80 C. The solution
was then cooled at room temperature, the precipitate was collected by
filtration and washed with distilled water and ethanol (96%) several
times. NP-ZnO was dried in the air at room temprature during 24 h [27].
2.2.2. General procedure for the preparation of nanosheet ZnO NS-ZnO
In a typical experiment, 1.32 g of NaOH was dissolved in 75 mL of
distilled water under vigorous stirring. Then the template, sodium
dodecylsulfate (SDS) (4.71 g) was added to the solution. Next
Zn(AcO)2.2H2O (1.8 g) was added to the mixture. The mixture was
transferred to a round bottomed flask and was refluxed for 1.5 h
(pH = 14). After cooling to room temperature, the precipitate was col-
lected by filtration and washed with distilled water and ethanol (96%)
several times. Finally, the ZnO sample was dried in the air at room tem-
perature during 24 h.
NP-ZnO
20
30
40
50
60
70
80
2θ
2.2.3. General procedure for the preparation of nanorod ZnO (NR-ZnO)
Sodium hydroxide (0.44 g) was dissolved in 75 mL of distilled water
under vigorous stirring at room temperature. Afterwards, with the
addition of SDS (1.57 g) and Zn(AcO)2.2H2O (0.6 g) to the mixture,
the solution was refluxed for 1.5 h at 80 C (pH = 14). The product
was collected by filtration and washed with distilled water and ethanol
(96%) several times [27].
Fig. 2. XRD spectra of ZnO nanostructures.
Diethyl 1-ethyl-5-phenyl-1H-pyrrole-2,3-dicarboxylate (4b). Brown
oil, yield: IR (KBr): ν = 1718, 1690, 1262 cm−1 1H NMR (250 MHz,
.
CDCl3): 1.28 (3H, t, 3JHH =7.0 Hz, Me), 1.31 (3H, t, 3JHH =7.1 Hz, Me),
1.46 (3H, t, 3JHH = 7.2 Hz, Me), 4.17–4.45 (6H, m, 3 CH2), 6.96 (1H, s,
CH), 7.29–7.51 (5H, m, 5 CH). 13C NMR (62.5 MHz, CDCl3): 14.1 (CH3),
14.2 (CH3), 17.0 (CH3), 44.5 (CH2N), 60.6 (CH2O), 61.1 (CH2O), 120.5
(C), 123.1)C), 123.2 (C), 124.7 (CH), 126.8 (CH), 127.4 (2 CH), 128.7
(2 CH), 133.5 (C), 160.2 (C = O), 166.8 (C = O) [13].
2.3. General procedure for the preparation of polysubstituted pyrroles
To a stirred mixture of amine (2 mmol), phenacyl bromide
(2 mmol) was added nanorod ZnO (15% mol). After 10 min dialkyl
acetylenedicarboxylate was added at 70 C temperature. The mixture
was stirred for about 60 min (TLC monitoring). The viscous residue
was purified by column chromatography on silica gel (Merck 230–400
mesh) using n-hexane-EtOAc (9:1) as eluent.
Dimethyl-1-benzyl-4-phenyl-1H-pyrrole-2,3-dicarboxylate (4c).
Brown oil, IR (KBr): ν = 1734, 1713, 1450 cm−1 1H NMR (250 MHz,
.
CDCl3): 3.82 (3H, s, Me), 3.87 (3H, s, Me), 5.53 (2H, s, CH2), 6.95 (1H,
s, CH), 7.1–7.50 (10H, m, 10 CH). 13C NMR (62.5 MHz, CDCl3): 51.9
(CH2N), 52.4 (CH3O), 54.2 (CH3O), 119.1 (C), 124.1 (C), 125.7 (CH),
127.0 (CH), 127.3 (2 CH), 127.4 (2 CH), 127.9 (2 CH), 128.7 (CH),
128.8 (2 CH), 130.7 (C), 133.6 (C), 137.2 (C), 161.2 (C = O), 166.2
(C = O) [13].
Diethyl 1-benzyl-4-phenyl-1H-pyrrole-2,3-dicarboxylate (4d).
Brown oil, IR (KBr): 1732, 1713, 1450, 1263 cm−1. 1H NMR (250 MHz,
CDCl3): 1.32 (3H, t, 3JHH =7.0 Hz, Me), 1.37 (3H, t, 3JHH =7.0 Hz, Me),
4.31 (2H, t, 3JHH =7.0 Hz, CH2), 4.37 (2H, t, 3JHH =7.0 Hz, CH2), 5.60
(2H, s, CH2), 6.99 (1H, s, CH), 7.2–7.48 (10H, m, 10 CH). 13C NMR
Dimethyl 1-ethyl-5-phenyl-1H-pyrrole-2,3-dicarboxylate (4a).
Brown oil. IR (KBr): ν = 1722, 1713, 1269 cm−1
.
1H NMR (250 MHz,
3
CDCl3): 1.44 (3H, t, JHH =7.0 Hz, Me), 3.83 (3H, s, Me), 3.84 (3H, s,
Me), 4.35 (2H, q, 3JHH = 7.0 Hz, CH2), 6.95 (1H, s, CH), 7.26–7.38 (5H,
m, 5 CH). 13C NMR (62.5 MHz, CDCl3): 16.9 (CH3), 44.6 (CH2N), 51.8
(CH2O), 52.4 (CH2O), 120.0 (C), 123.7 (CH), 124.8 (C), 126.9 (CH),
127.3 (2 CH), 128.7 (2 CH), 128.7)C),133.5 (C), 160.6 (C = O), 167.5
(C = O) [14].
Fig. 1. SEM images of the samples obtained by the reflux method without template nanoparticle (NP-ZnO) or with using SDS template nanosheet (NS-ZnO) and nanorod (NR-ZnO).

118
M. Sabbaghan, A. Ghalaei / Journal of Molecular Liquids 193 (2014) 116–122
Scheme 1. ZnO catalyzed synthesis of pyrrole.
(62.5 MHz, CDCl3): 14.1 (CH3), 14.2 (CH3), 52.4 (CH2N), 60.7 (CH2O),
61.3 (CH2O), 121.2 (C), 123.9 (C), 125.6 (CH), 126.9 (CH), 127.4
(2 CH), 127.5 (2 CH), 127.9 (CH), 128.6 (2 CH), 128.8 (2 CH), 130.1
(C), 134.0 (C), 137.1 (C), 160.3 (C = O), 166.9 (C = O). MS (EI,
70 eV): m/z (%) = 377 (M+, 15), 291 (50), 287 (100), 215 (100), 226
(40), 125 (62), 66 (70), 57 (80). Anal. Calcd for C23H23NO4 (377.43):
C, 73.19; H, 6.14; N, 3.71. Found: C, 73.40; H, 6.12; N, 3.75%.
Diethyl-1-hexyl-5-phenyl-1H-pyrrole-2,3-dicarboxylate (4 h).
Brown oil, IR (KBr): ν = 1730, 1709, 1489, 1263 cm−1 1H NMR
.
(250 MHz, CDCl3): 0.89 (3H, t, 3JHH =7.8 Hz, Me), 1.25–1.37 (12H, m,
6 CH2), 1.79 (2H, m, CH2), 4.25–4.33 (6H, m, 3 CH2), 6.91 (1H, s, CH),
7.3–7.42 (5H, m, 5 CH). 13C NMR (62.5 MHz, CDCl3): 14.1 (CH3), 14.1
(CH3), 14.2 (CH3), 22.6 (CH2), 26.4 (CH2), 31.4 (CH2), 31.6 (CH2), 49.7
(CH2N), 60.6 (CH2O), 61.3 (CH2O), 120.5 (C), 123.3 (C), 125.4 (CH),
126.8 (CH), 127.4 (2 CH), 128.6 (2 CH), 128.9 (C), 133.6 (C), 160.2
(C = O), 167.1 (C = O). MS (EI, 70 eV): m/z (%) = 371 (M+, 20),
299 (68), 251 (100), 227 (40), 165 (40), 86 (62), 86 (68), 58 (45), 57
(50), 29 (44). Anal. Calcd for C22H29NO4 (371.47): C, 71.13; H, 7.87; N,
3.77. Found: C, 71.10; H, 7.81; N, 3.75%.
Diethyl 1-(4-chlorobenzyl)-4-phenyl-1H-pyrrole-2,3-dicarboxylate
(4e). Brown oil, IR (KBr): 1740, 1732, 1484, 1257 cm−1 1H NMR
.
(250 MHz, CDCl3): 1.28–1.33 (6H, m, 2 Me), 4.21–4.33 (4H, m, 2 CH2),
5.50 (2H, s, CH2), 6.94 (1H, s, CH), 7.2–7.48 (9H, m, 9 CH). 13C NMR
(75 MHz, CDCl3): 13.9 (CH3), 14.0 (CH3), 51.7 (CH2N), 60.7 (CH2O),
61.3 (CH2O), 120.9 (C), 122.8 (C), 124.1 (CH), 125.4 (CH), 126.9 (2 CH),
127.4 (2 CH), 127.9 (CH), 128.6 (2 CH), 128.6 (2 CH), 130.7 (C), 133.2
(C), 133.7 (C), 160.2 (C = O), 166.7 (C = O). MS (EI, 70 eV): m/z
(%) = 413 (M+, 15), 411 (M+, 5), 357 (22), 355 (7), 269 (100), 267
(33), 157 (40), 143 (61), 67 (60), 42 (50). Anal. Calcd for C23H22ClNO4
(411.12): C, 67.07; H, 5.38; N, 3.40. Found: C, 67.01; H, 5.22; N, 3.38%.
Diethyl 1-(4-methylcyclohexa-1,5-dienyl methyl)-4-phenyl-1H-
pyrrole-2,3-dicarboxylate (4f). Brown oil, IR (KBr): 1732, 1713, 1450,
1263 cm−1. 1H NMR (250 MHz, CDCl3): 1.22–1.39 (6H, m, 2 Me), 2.33
(3H, s, Me) 4.18–4.35 (4H, m, 2 CH2), 5.49 (2H, s, CH2), 6.91 (1H, s,
CH), 7.2–7.48 (9H, m, 9 CH). 13C NMR (75 MHz, CDCl3): 14.0 (CH3),
21.1 (CH3), 52.1 (CH2N), 61.2 (CH2O), 61.9 (CH2O), 121.1 (C), 122.4
(C), 123.8 (CH), 125.4 (CH), 126.8 (2 CH), 127.4 (2 CH), 128.0 (CH),
128.5 (2 CH), 128.8 (2 CH), 129.4 (C), 130.1 (C), 133.5 (C), 133.9 (C),
Diethyl 1-ethyl-5-(4-methoxyphenyl-1H-pyrrole-2,3-dicarboxylate
(4i). Brown oil. IR (KBr): ν = 1729, 1713, 1579, 1297 cm−1 1H NMR
.
(250 MHz, CDCl3): 1.26–1.35 (9H, m, 3 Me), 3.81 (3H, s, OMe), 4.24–
4.32 (6H, m, 3 CH2), 6.84 (1H, s, CH), 6.88 (2H, d, 3JHH =6.4 Hz, 2 CH),
3
7.32 (2H, d, JHH =6.4 Hz, 2 CH). 13C NMR (62.5 MHz, CDCl3): 14.0
(CH3), 14.1 (CH3), 14.1 (CH3), 49.5 (CH2N), 55 (OMe), 60.5 (CH2O),
61.1 (CH2O), 113.9 (2 CH), 124.9 (C), 125.0)C), 126.0 (CH), 126.5 (C),
128.6 (2 CH), 133.0 (C), 153.0 (C), 158.5 (C = O), 160.2 (C = O). MS
(EI, 70 eV): m/z (%) = 345 (M+, 20), 328 (68), 282 (100), 256 (100),
226 (40), 133 (62), 85 (68), 71 (70), 57 (100). Anal. Calcd for
C
19H23NO5 (345.38): C, 66.07; H, 6.71; N, 4.06. Found: C, 66.37; H,
6.04; N, 4.08%.
Dimethyl 1-ethyl-5-(4-chlorophenyl-1H-pyrrole-2,3-dicarboxylate
(4j). Brown oil, IR (KBr): ν = 1709, 1697, 1400, 1263 cm−1
.
1H NMR
160.3 (C = O), 166.9 (C = O). MS (EI, 70 eV): m/z (%) = 391 (M+
,
(250 MHz, CDCl3): 1.40 (3H, t, JHH =7.0 Hz, Me), 3.76 (3H, s, Me),
3
10), 363 (52), 291 (100), 247 (100), 171 (48), 125 (52), 66 (72), 57
(82). Anal. Calcd for C24H25NO4 (391.16): C, 73.61; H, 6.38; N, 3.55.
Found: C, 73.64; H, 6.44; N, 3.58%.
3.77 (3H, s, Me), 4.35 (2H, q, 3JHH = 7.2 Hz, Me), 6.43 (2H, d, 3JHH
=
C
3
7.0 Hz, 2 CH), 6.92 (1H, s, CH), 7.25 (2H, d, JHH =7.0 Hz, 2 CH). 13
NMR (62.5 MHz, CDCl3): 16.9 (CH3), 44.6 (CH2N), 51.9 (CH3O), 52.5
(CH3O), 119.1 (C), 122.5 (C), 124.7 (CH), 128.7 (2 CH), 128.8 (2 CH),
129.6 (C), 130.5)C),131.5 (C), 161.2 (C = O), 166.5 (C = O). MS (EI,
70 eV): m/z (%) = 323 (M+, 32), 321 (M+, 10), 265 (48), 235 (88),
178 (38), 165 (40), 183 (52), 197 (60), 86 (68), 56 (45). Anal. Calcd
for C16H16NO4Cl (321.75): C, 59.73; H, 5.01; N, 4.35. Found: C, 59.65;
H, 5.02; N, 4.15%.
Dimethyl-1-hexyl-5-phenyl-1H-pyrrole-2,3-dicarboxylate (4 g).
Brown oil, IR (KBr): ν = 1716, 1694, 1540, 1267 cm−1 1H NMR
.
(250 MHz, CDCl3): 0.89 (3H, t, 3JHH =7.8 Hz, Me), 1.26–1.42 (6H, m, 3
CH2), 1.79 (2H, m, CH2), 3.82 (3H, s, Me), 3.83 (3H, s, Me), 4.3 (2H, t,
3JHH =7.0 Hz, CH2), 6.91 (1H, s, CH), 7.26–7.40 (5H, m, 5 CH). 13C
NMR (62.5 MHz, CDCl3): 14.1(CH3), 22.6 (CH2), 26.4 (CH2), 31.4
(CH2), 31.6 (CH2), 49.7 (CH2N), 51.8 (CH3O), 52.4 (CH3O), 120.2 (C),
123.5 (CH), 125.5 (C), 126.9 (CH), 127.3 (2 CH), 128.7 (2 CH), 130.1
(C), 133.5 (C), 160.3 (C = O), 167.3 (C = O). MS (EI, 70 eV): m/z
(%) = 343 (M+, 25), 287 (68), 285 (100), 257 (100), 251 (40), 181
(62), 125 (68), 67 (70), 58 (35), 29 (44). Anal. Calcd for C20H25NO4
(343.41): C, 69.95; H, 7.34; N, 4.08. Found: C, 66.89; H, 7.16; N, 4.18%.
100
90
80
70
60
50
40
30
20
10
0
Table 2
Optimization of reaction condition using different morphologies of ZnO (12 mol%) at
50 °C during 1 h.
Entry
Catalyst
Yield (%)
1
2
3
4
5
none
0
25
35
50
70
80
100
CM-ZnO
NS-ZnO
NP-ZnO
NR-ZnO
62
80
80
85
Temperature (°C)
Fig. 3. Influence of reaction temperature on the synthesis of polysubstituted pyrroles.

M. Sabbaghan, A. Ghalaei / Journal of Molecular Liquids 193 (2014) 116–122
119
100
90
80
70
60
50
40
30
20
10
0
displayed a diameter of ~30 nm, length of ~700 nm and ~400 nm in
width. Fig. 2 shows the XRD pattern of ZnO with typical morphologies
synthesized by this method. All the prominent peaks in the pattern
corresponded to the wurtzite structure of ZnO, which can be indexed
on the basis of JCPDS file No. 36–1451. No other characteristic peaks of
the impurities are observed, indicating the high purity of the catalysis.
We observe that all samples exhibit highest relative intensities for the
(1 0 1) peak revealing a preferred orientation of their corresponding
products. While, comparing with other peaks, the samples show differ-
ent relative intensities of the (0 0 2) peak. The average crystal sizes for
NP-ZnO, NS-ZnO, NR-ZnO are about 30, 21, 30 nm respectively [26,27].
It seems that the formation of ZnO with different morphologies in-
volves the interaction between “nucleus” and SDS to control the growth
rate in a certain direction [27]. An explanation for the formation of
nanosheet ZnO involves the role of precursor and the SDS to control
the growth rate of various faces of the preformed nucleus. The SDS mol-
ecules firstly form bilayers in the precursor solution, that SDS molecules
form bilayer-like micelles in concentrated solution. The head group re-
gions of the formed micelles are occupied by coulombic force with pre-
cursor. At the moment, formation of Zn(OH)24− nuclei takes place in the
head group regions of the micelles, resulting in uniform nano-sheets
[28]. It seems that the NR-ZnO morphology results in cylindrical inverse
micelles in aqueous solutions of SDS [29].
0
5
10
15
20
NR-ZnO (mol %)
Fig. 4. Effect of catalyst loading on the synthesis of pyrrole, reaction conditions: Ethyl
amine (1 mmol), DEAD (1 mmol), phenacyl bromide (1 mmol), solvent free, 70 °C, 1 h.
Table 3
One-pot synthesis of N-benzyl-2-[(2-oxoethyl-2-phenyl)amino] benzamide at different
solvent during 1 h with NR-ZnO (12 mol%).
Entry
Solvent
Temperature (°C)
Yield (%)
3.2. Catalytic activity of ZnO nanostructures in the synthesis of
polysubstituted pyrroles
1
2
3
4
5
CH3CN
H2O
CH2Cl2
n-Hexane
Solvent-free
Reflux
Reflux
Reflux
Reflux
70
84
40
45
60
94
Initially, benzyl amine, phenacyl bromide and diethyl acetylene-
dicarboxylate (DEAD) were chosen as the model reaction (Scheme 1)
and commercial zinc oxide (CM-ZnO) was used as the catalyst. It was
found to give 62% yield of product at 50 °C under solvent free condition
(Table 1, entry 2). Encouraged by this result, further optimization
studies were carried out by nanostructures of ZnO with different mor-
phologies including nanoparticle (NP-ZnO), nanorod (NR-ZnO) and
nanosheet ZnO (NS-ZnO) as catalyst.
3. Results and discussion
3.1. Design, preparation and characterization of the catalysts
The method of synthesis of NR-ZnO and NP-ZnO was reported in our
last article [27]. ZnO nanoparticles were obtained from the reaction be-
tween Zn(AcO)2 · 2H2O and NaOH by reflux method without adding
template. Nanorod morphology was obtained using SDS [27]. Nano-
sheet ZnO (NS-ZnO) was synthesized by increasing the reactants and
SDS to solvent ratio. This is reported in this article. SDS was employed
as a directing agent to control ZnO nanostructure morphologies. The
corresponding experimental condition and morphologies of samples
are listed in Table 1. The morphologies of the products were examined
by SEM. Fig. 1 shows the typical SEM images of the samples obtained
by the reflux method. As shown in this figure, when only Zn+2 was
used (without any template), ZnO nanoparticles were formed. Using
SDS, ZnO nanorod was obtained in the same condition. The length and
diameter of nanorods were 300–600 nm and 50–70 nm, respectively.
SEM image of NS-ZnO prepared in SDS clearly shows homogeneous
samples with uniform nanosheet morphology. These nanosheets
As shown in Table 2, the reaction did not take place without any
catalyst (Table 2, entry 1) and the yield of the desired product was max-
imized when NR-ZnO was used (Table 2, entry 5).
The result of changing the reaction temperature is visualized in Fig. 3
when NR-ZnO was used. The best reaction temperature is between 70
and 80 °C. Thus, this reaction was carried out at the lower temperature,
i.e., at 70 °C.
The result of our optimization studies in catalyst loading is presented
in Fig. 4. The yield increased smoothly with catalyst load up to 15% but
further increase led to the decrease of product conversion. The results
indicate the significant role of NR-ZnO as a catalyst for the reaction.
To understand the role of solvent, we screened various solvent sys-
tems, such as CH3CN, H2O, CH2Cl2 and n-hexane (Table 3). The results
showed that polar solvents such as CH3CN gave higher yields comparing
to another solvents. However, the amount of desired product was found
to be greater in solvent-free condition.
Scheme 2. NR-ZnO catalyzed synthesis of pyrrole in optimum condition.

120
M. Sabbaghan, A. Ghalaei / Journal of Molecular Liquids 193 (2014) 116–122
Table 4
Substrate scope, reaction conditions: phenacyl bromide (1.0 mmol), amine (1 mmol), dialkyl acetylenedicarboxylate (1.0 mmol), NR-ZnO (15%), Solvent free, 70 C.
Entry
α-Bromo ketone
Amines
Acetylene dicarboxylate
Product
Time
(min)
Yielda
(%)
1
45
90
4a
2
45
88b
4b
3
50
50
90
4c
4
94
4d
5
60
82
4e
6
60
86
4f
7
45
92
4g
8
45
86

M. Sabbaghan, A. Ghalaei / Journal of Molecular Liquids 193 (2014) 116–122
121
Table 4 (continued)
Entry
α-Bromo ketone
Amines
Acetylene dicarboxylate
Product
Time
Yielda
(min)
(%)
4h
9
60
60
75
4i
10
78
4j
11
360
0
4k
12
360
0
4l
13
60
0
4m
a
Isolated yield. 4a–c are known compounds [13–14].
Yield obtained after 3 catalytic cycles.
b
To extend the scope, NR-ZnO was tested with various amines,
of diethyl 1-ethyl-5-phenyl-1H-pyrrole-2,3-dicarboxylate (Table 4,
entry 2). The catalyst was filtered off after each run and washed
thoroughly with ethylacetate; it was then dried at room temperature
for 24 h and used for the next catalytic cycle.
phenacyl bromide with dialkyl acetylenedicarboxylate and the resulting
products were formed in high yield (Scheme 2, Table 4). All the prod-
ucts obtained were fully characterized by spectroscopic methods such
as IR, 1H NMR, 13C NMR and mass spectroscopy. The yields of products
were in the range of 75–94% and the reaction time varies depending
upon the nature of the substrate. Aromatic amines didn't give the de-
sired products (Table 4, entries11 and 12). Also the reaction with
ethyl bromopyruvate was not successful (Table 4, entry 13).
Mechanistically, it is conceivable that the reaction involves the initial
formation 5 between the amine and the electron-deficient acetylenic
compound, which reacts with the phenacyl bromide to generate 6
[13]. Cyclization of this intermediate followed dehydration, which af-
fords 1,2,3,5-substituted pyrroles. NR-ZnO has Lewis acid sites (Zn2+
)
The catalyst can be resolved three times without significant loss of
activity. The reusability of the catalyst was checked for the synthesis
and Lewis basic sites (O2−) [24,30]. In this reaction, the Zn2+ sites are
interacting with carbonyl groups in acetylenic compound and phenacyl

122
M. Sabbaghan, A. Ghalaei / Journal of Molecular Liquids 193 (2014) 116–122
Scheme 3. Proposed mechanism of formation of three-substituted pyrroles catalyzed by ZnO nanostructures.
bromide and O2− site of ZnO nanostructures taking up a proton of 7 to
generate 4 (Scheme 3) [30]. The detailed formation mechanism of prod-
uct needs to be further investigated.
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4. Conclusions
Herein, we disclose a general, rapid, high yielding and green synthetic
protocol for synthesis of three-substituted pyrrole derivatives via the one-
pot three-component reactions of amine, phenacyl bromide and dialkyl
acetylenedicarboxylates under solvent free conditions using nanorod
ZnO. The efficiency of the catalytic activity is dependent on the particle
size and morphology of ZnO. Low temperature in catalyst synthesis and
pyrrole preparation is interesting from an economic point of view. Devel-
opment of such catalysts has resulted in more economical and environ-
mentally friendly chemistry replacing unstable or toxic catalysts.
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