Monatsh Chem (2013) 144:405–409
DOI 10.1007/s00706-012-0841-2
ORIGINAL PAPER
Squaric acid catalyzed simple synthesis of N-substituted pyrroles
in green reaction media
•
Najmadin Azizi Anahita Davoudpour
•
•
Farshid Eskandari Ehlham Batebi
Received: 6 November 2011 / Accepted: 15 August 2012 / Published online: 22 September 2012
Ó Springer-Verlag 2012
Abstract An operationally simple and efficient protocol
for squaric acid catalyzed synthesis of N-substituted pyr-
roles via the reaction of 2,5-dimethoxytetrahydrofuran and
2,5-hexandione with aryl amines in green reaction media
(water, deep eutectic solvent, and polyethylene glycol)
under ultrasound irradiation or thermal conditions in good
to excellent yields has been developed.
moisture and oxygen, demanding reaction conditions, for
example inert atmosphere, low temperatures, absolute
solvents, etc., are, in many instances, not required. Because
of the absence of transition metals, organocatalytic meth-
ods seem to be especially attractive for the preparation of
drug-like compounds [4, 5].
Pyrrole containing heterocycles are an important class of
compounds displaying remarkable pharmacological prop-
erties such as antibacterial, antiviral, anti-inflammatory,
antitumoral, and antioxidant activities [6]. Furthermore,
they are useful intermediates in the synthesis of natural
products [7] and are also widely used in material science
[8]. Consequently, an enormous number of procedures
have been developed for the construction of pyrroles in the
literature [9–12]. Despite these new developments, the
Paal–Knorr reaction [13] remains one of the most attractive
methods for the synthesis of N-substituted pyrroles [14–
26]. In an attempt to design a green, pronounced procedure
to synthesize N-arylpyrrole derivatives in green reaction
media, many methods in green solvents such as ionic
liquid, water, and solventless conditions have been used to
synthesize pyrrole derivatives in different reaction condi-
tions (Table 1).
Keywords Aromatic amine Á Green chemistry Á
Pyrrole Á Squaric acid Á Novel organocatalyst
Introduction
Developments of eco-friendly methodologies which are
environmentally clean, waste-free, high purity, and prevent
pollution have received much attention in recent years. To
reach this goal, the use of green reaction media, reagents,
and catalysts should be investigated. By applying alterna-
tive reaction conditions, more efficient processes and new
catalysts can be discovered allowing the preparation of
innovative materials. Water, a unique solvent in organic
synthesis, is not only abundant, inexpensive and environ-
mentally benign, but also shows novel reactivity and
selectivity for simple synthesis of organic compounds such
as pharmaceutical products, agrochemicals, fine chemicals,
and synthetic intermediates [1–3].
Results and discussion
On the other hand, organocatalysts have several
advantages. They are usually robust, inexpensive, readily
available, and non-toxic. Because of their inertness toward
In our continuing effort to utilize green solvents as envi-
ronmentally attractive media in organic synthesis [27–29],
herein we developed a novel organocatalyst (squaric acid)
[30] for an efficient preparation of N-arylpyrroles from the
reaction of aromatic amines with 2,5-dimethoxytetrahy-
drofuran (1) and 2,5-hexandione (4) in green reaction
media: water, deep eutectic solvent (DES), and polyethyl-
ene glycol (PEG).
N. Azizi (&) Á A. Davoudpour Á F. Eskandari Á E. Batebi
Chemistry and Chemical Engineering Research Center of Iran,
P.O. Box 14335-186, Tehran, Iran
e-mail: azizi@ccerci.ac.ir
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