Tetrahedron Letters
A new protocol for one-pot synthesis of tetrasubstituted pyrroles
using tungstate sulfuric acid as a reusable solid catalyst
⇑
Mahnaz Farahi , Mahdiyeh Davoodi, Mina Tahmasebi
Department of Chemistry, Yasouj University, Yasouj 75918-74831, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of tetrasubstituted pyrroles were synthesized in good yields in a one-pot, three-component
Received 26 December 2015
Revised 22 February 2016
Accepted 26 February 2016
Available online xxxx
reaction of
(TSA) under solvent-free conditions.
a-hydroxyketones, malononitrile, and ammonium acetate using tungstate sulfuric acid
Ó 2016 Published by Elsevier Ltd.
Keywords:
Tetrasubstituted pyrroles
a-Hydroxyketones
Malononitrile
Ammonium acetate
Tungstate sulfuric acid
In recent decades, derivatives of pyrrole have gained wide-
spread attention as basic constituents of numerous natural prod-
features make them appropriate for the simple and efficient syn-
thesis of complex heterocyclic compounds.
ucts such as heme, chlorophyll, vitamin B12
,
and various
Nowadays, because of an increase in environmental awareness
in chemical research and industry, attention has been focused on
the use of reusable heterogeneous catalysts in organic transforma-
tions.16 Heterogeneous catalysts have advantages such as easy sep-
aration from the reaction mixture, recyclability, non-toxicity, ease
of use, storage safety, long shelf-life, and tolerance of a wide range
of temperatures and pressures.17–19 Tungstate sulfuric acid (TSA) is
a heterogeneous alternative to sulfuric acid, synthesized by the
reaction of anhydrous sodium tungstate with chlorosulfonic acid.20
TSA is a safe, stable, and recyclable solid acid catalyst which has
been used in various organic transformations.21,22
cytochrome enzymes.1–3 Pyrroles are also valuable intermediates
in organic synthesis.4,5 Furthermore, they are found in drugs such
as tolmetin, atorvastatin, and tallimustine.6 Substituted pyrroles
exhibit a broad spectrum of biological properties and possess anti-
tumor, antibacterial, and cytotoxic activities.7–9 Indeed, the mode
of biological activity of various pyrroles depends on the nature
and position of the substitution. Therefore, the development of
novel strategies aimed at the synthesis of diversely substituted
pyrroles is still of practical importance.10–12
A major challenge in modern chemistry is the design of highly
efficient chemical reactions with the minimum number of syn-
thetic steps and short reaction times. Multi-component reactions
have been developed as a powerful strategy in combinatorial,
medicinal, and organic chemistry as they address essential princi-
ples of synthetic efficiency.13,14 These reactions represent useful
tools for the synthesis of complex molecules with potential biolog-
ical properties because of their effective atom economy, conver-
gent nature, time saving, and straightforward experimental
procedures.15 Multi-component reactions often have short reaction
times and give higher yields than multiple-step syntheses, and
hence result in a decreased use of energy and manpower. These
As part of our current studies on the development of new routes
in heterocyclic synthesis,12,23,24 herein, we describe the one-pot
reaction between
a-hydroxyketones (1), ammonium acetate (2),
and malononitrile (3) in the presence of TSA to afford tetrasubsti-
tuted pyrroles (Scheme 1).
Ar
Ar
CN
NH
Ar
Ar
O
NC
TSA (5 mol%)
NH OAc
4
solvent-free
70 °C
2
N
H
NC
3
OH
1
2
4
O
W
O
TSA : HO SO
OSO H
3
3
⇑
Corresponding author. Tel.: +98 7412223048; fax: +98 7412242167.
Scheme 1. TSA-catalyzed one-pot synthesis of tetrasubstituted pyrroles 4.
0040-4039/Ó 2016 Published by Elsevier Ltd.