Polyethylene glycol (PEG-400) as an efficient and recyclable reaction medium for one-pot synthesis of substituted pyrroles under catalyst-free conditions

Article abstract of DOI:10.14233/ajchem.2015.18334

Polyethylene glycol (PEG-400) was found to be an effective and nontoxic reaction medium for the one-pot synthesis of substituted pyrroles under catalyst-free conditions in excellent yields. Environmental acceptability, low cost, high yields and recyclabil

Full text of DOI:10.14233/ajchem.2015.18334

Asian Journal of Chemistry; Vol. 27, No. 4 (2015), 1457-1461
A
SIAN
J
OURNAL OF HEMISTRY
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http://dx.doi.org/10.14233/ajchem.2015.18334
Polyethylene Glycol (PEG-400) as an Efficient and Recyclable Reaction Medium
for One-Pot Synthesis of Substituted Pyrroles Under Catalyst-Free Conditions
1,*
1
2
1
TULAM VIJAYA KUMAR , CH. RAMA KOTESWARA RAO , K. MUKKANTI and PRATHAMA S. MAINKAR
1Evolva Biotech Private Limited, TICEL Bio Park Limited, Taramani, Chennai-600 113, India
2Centre for Chemical Sciences andTechnology, Institute of Science andTechnology, Jawaharlal NehruTechnological University-Hyderabad, Kukatpally,
Hyderabad-500 085, India
*Corresponding author: Tel/Fax: +91 44 42971050/60; E-mail: vijaykumar.thulam@gmail.com
Received: 16 June 2014;
Accepted: 26 September 2014;
Published online: 4 February 2015;
AJC-16814
Polyethylene glycol (PEG-400) was found to be an effective and nontoxic reaction medium for the one-pot synthesis of substituted
pyrroles under catalyst-free conditions in excellent yields. Environmental acceptability, low cost, high yields and recyclability of the
polyethylene glycol are the important features of this protocol.
Keywords: Pyrroles, Aniline, Nitrostyrene, Acetyl acetone, Polyethylene glycol, Catalyst-free conditions.
previous reports on the synthesis of substituted pyrroles using
polyethylene glycol-400 as a reaction medium under catalyst-
free conditions. We report herein the synthesis of substituted
pyrroles via tandem Michael addition-cyclization using PEG-
400 as a recyclable medium without any additional organic
solvent and catalyst.
INTRODUCTION
The pyrrole ring represents an important class of structural
unit which is frequently found in many natural products1,
biologically and pharmaceutically active compounds2,3. It has
been widely used as antitumor4, antiinflammatory5,6, anti-
bacterial7, antioxidant8, and antifungal agents9. In addition, they
are also useful in building blocks which are extensively used
in material science10,11. The synthesis of pyrroles and their
derivatives is usually achieved by well-known methods like
Hantzsch12,13 or Knorr14, or Paal Knorr15 reaction. The synthesis
of tetra substituted pyrrole derivatives has been reported by
Jana and co-workers by employing four-component reaction
catalyzed by FeCl316 or palladium mediated Suzuki reaction
based on multicomponent reaction17. Menendez and his co-
workers18 reviewed the synthesis of pyrroles and their deriva-
tives through multicomponent reactions (MCRs). Many of the
methods possess drawbacks such as harsh reaction conditions,
tedious experimental procedures, unsatisfactory yields, long
reaction times or use of expensive and moisture sensitive cata-
lysts. Hence, there is a need for the rapid and efficient method
of the synthesis of substituted pyrroles under catalyst-free
conditions.
EXPERIMENTAL
All the chemicals employed in this study were procured
from Sigma Aldrich and Alfaesear. In present study, all the
synthetic reactions were monitored by TLC and synthesized
compounds were confirmed by various spectroscopic methods.
The IR spectra were recorded using KBr pellets on a Perkin
Elmer IR spectrophotometer. 1H NMR spectra were recorded
on Brucker 300 MHz Avance NMR spectrophotometer using
CdCl3 as solvent and TMS as internal standard (chemical shifts
in d ppm). The mass spectra were recorded on Agilent 6300
series ion trap.
General procedure: The mixture of aniline (0.186 g,
2 mmol), nitrostyrene (0.149 g, 1 mmol), and acetyl acetone
(0.120 g, 1.2 mmol) was taken in 5 mL polyethyleneglycol-
400. The resulting mixture was allowed to stir at 85 °C for 8 h.
After completion of the reaction, as monitored by TLC, the
reaction mixture was poured into water and extracted with
ethyl acetate. The organic layer was removed under reduced
pressure and the crude product was purified by column chro-
matography on silica gel using ethyl acetate: hexane mixture
(3:7) as eluent to yield the desired product.
In recent years, polyethylene glycol (PEG) has emerged
as a powerful phase-transfer catalyst and performs many useful
organic transformations under mild reaction conditions.
Moreover, polyethylene glycol is inexpensive, easy to handle,
thermally stable, nontoxic and recyclable for various organic
transformations. To the best of our knowledge there are no

1458 Kumar et al.
RESULTS AND DISCUSSION
Asian J. Chem.
progress of reaction was monitored byTLC, the reaction mixture
was poured into water and extracted with ethyl acetate. The
organic layer was removed under reduced pressure and the crude
product was purified by column chromatography on silica gel
using ethyl acetate: hexane mixture (3:7) as eluent to yield 92 %
of the desired product. (Scheme-I, entry-1 in Table-1).
We first attempted the reaction between simple aniline, nitro-
styrene and acetyl acetone. The mixture of aniline, nitrostyrene
and acetyl acetone was taken in 5 mL polyethylene glycol- 400.
The resulting mixture was allowed to stir at 85 °C for 8 h. The
Entry
Aniline
Nitrostyrene
Acetylacetone
Product
Time (h) Yield (%)
O
NH
2
NO
O
O
2
1
8
8
92
H C
CH
3
3
N
O
O
N
NH
O
2
O
O
NO
2
O
O
85
2
H C
CH
3
3
O
O
N
NH
O
2
O
O
O
O
NO
NO
NO
85
8
2
3
H C
CH
3
3
F
F
O
N
NH
2
O
O
2
O
O
O
O
O
O
90
7
4
H C
3
CH
CH
CH
3
3
3
O
N
NH
2
O
O
2
7
90
5
H C
3
O
NH
2
F
O
O
NO
2
6
H C
85
8
N
3
F

Vol. 27, No. 4 (2015)
One-Pot Synthesis of Substituted Pyrroles Under Catalyst-Free Conditions 1459
O
NH2
NO2
O
O
Br
7
8
8
85
85
H3C
CH3
Br
N
O
H2N
NO2
O
O
N
8
H3C
CH3
F
O
H2N
O
O
NO2
NO2
NO2
85
8
9
H3C
CH3
N
F
NO2
O
H2N
O
O
90
7
N
10
H3C
CH3
O2N
O
O
NH2
O
O
OMe
N
7
90
11
H3C
CH3
OMe
O
Cl
NH2
Cl
O
O
OMe
NO2
12
H3C
CH3
85
8
N
OMe

1460 Kumar et al.
Asian J. Chem.
O
O
NH
2
O
O
O
13
8
85
H C
CH
3
3
N
NO
2
O
O
NH
Cl
2
O
O
NO
2
8
85
H C
CH
3
14
3
N
O
O
Br
NH
Cl
2
NO
8
2
85
O
O
15
H C
3
CH
3
N
Br
Cl
O
O
NH
2
NO
2
O
O
16
7
90
N
H C
3
CH
3
O
O
R
2
H
C
3
R
2
O
O
PEG-400(5mL)
85C, 8h
R
NH
2
1
+
+
H C
3
N
R
H C
CH
NO
3
3
2
1
Scheme-I: PEG mediated synthesis of substituted pyrroles
The generality of this reaction was investigated by using
wide variety of functionalized anilines and nitroolefines and
the results are presented in Table-1.
The generality of solvent screening was done with the
same example with variety of solvent medium and observed
that the ethylene glycol is the best medium; results were
mentioned in Table-2.
In general, all the reactions were very clean and the substi-
tuted pyrrole derivatives were obtained in high yields. anilines
bearing electron-donating groups such as CH3 and OCH3,
reacted efficiently (Scheme-II); whereas in the presence of
Scheme-II: A plausible reaction pathway
electron-withdrawing groups NO2, a slight decrease in the yield
of the substituted pyrroles was observed (Table-1 entries 6, 7,

Vol. 27, No. 4 (2015)
One-Pot Synthesis of Substituted Pyrroles Under Catalyst-Free Conditions 1461
TABLE-2
COMPARISON OF SOLVENTS IN
THE SYNTHESIS OF PYRROLE
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The authors are thankful to the Management of Evolva
Biotech Pvt. Ltd, India and Institute of Science and Technology
Jawaharlal Nehru Technological University, Hyderabad, India
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