Catalysis Communications
Short Communication
[bmIm]OH catalyzed hetero-cyclisation of o-halobenzoic acid and
alkyne: A green approach to synthesize isocoumarins
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Malik A. Waseem, Shireen, Afaf A. Abumahdi, Arjita Srivastava, Anjali Srivastava, Rahila, I.R. Siddiqui
Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 April 2014
Received in revised form 10 June 2014
Accepted 11 June 2014
Available online 21 June 2014
Efficient and environmentally benign heterocyclization of o-halobenzoic acid and alkyne has been developed
using [bmIm]OH as green catalyst. This methodology offers a metal and base free approach and is endowed
with mild reaction conditions, high yields and better functional group tolerating ability. The recyclability and
reuse of [bmIm]OH add the methodology a wide scope.
© 2014 Elsevier B.V. All rights reserved.
Keywords:
Basic ionic liquid ([bmImOH])
Isocoumarin
Heterocycle Green Protocol
Ambient conditions
1. Introduction
However, most of the reported methodologies have drawbacks, which
include, use of expensive and hazard catalysts such as copper(II)chloride,
Recent advancement of ionic liquids (ILs) as catalyst, solvent and
base has opened new vistas in the field of synthetic chemistry research
[1–3]. A wide range of heterocycles including spirothiazines, indolizines,
quionolines, and many more vital heterocycles have been synthesized
using this approach [4–6]. The growing attention of ionic liquids is by
their tuneable features like complete recovery, reusability, negligible
vapor pressure, wide solvating capability, multiple bond forming effi-
ciency and many other green credentials such as alternative reaction
media to molecular solvents, catalysts and reagents [1–3]. Recently
our research group has developed [bmIm]OH catalyzed intramolecular
heterocyclization leading to the synthesis of biologically recognized
substituted benzofuran derivatives [7]. Continuing our work on ionic
liquid promoted heterocycle synthesis, we decided to develop eco-
compatible ionic liquid promoted strategy for the synthesis of biologi-
cally recognized isocoumarins.
Isocoumarins are an elite class of heterocyclic compounds with
astounding biological significance. Anti-cancer, anti-hypertensive, anti-
clotting, hepatoprotective, and anti-viral activities are prominent
among them [8–15]. In addition, isocoumarin derivatives are useful
precursors for the synthesis of various natural products, these natural
products have an immense scope in the biological world. Thus
because of strong requirement of 3, 4-disubstituted isocoumarins
in medicament and natural product synthesis, a number of methods
are available in literature for the construction of isocoumarin derivatives.
indium(III)chloride, bismuth(III)nitrate-penta hydrate, ruthenium,
palladium and rhodium [16–23]. Further carcinogenic volatile organic
solvents (VOLs), complex starting materials, and drastic reaction condi-
tions remained the scientific challenge. Therefore an easy, eco-friendly
and practical method for the synthesis of isocoumarin derivatives
would be highly desirable and useful at present.
To circumvent the above mentioned drawbacks for the construction
of isocoumarins as well as in continuation of our research program for
the development of simple, versatile synthetic methodology for biody-
namic heterocyclic scaffolds, [24–35] herein we report a simple and
highly efficient strategy for the synthesis of 3,4 isocoumarin derivatives
by [bmIm]OH catalyzed addition of o-halobenzoic acids to internal
alkyne (Scheme 1).
In this reaction O\C and C\C bonds were formed simultaneously to
afford isocoumarins in moderate to good yields. The synthesized core
moiety is well tolerated by diverse functional groups (Table 3). These
functional groups were easily converted to useful functional groups
that produce drug like library of compounds and add the applied
methodology a wide scope.
Initially the reaction was performed by using o-iodobenzoic acid and
the symmetrical alkyne, (DMAD) as model reactants in 25 mol% of basic
ionic liquid, ([bmIm]OH) as solvent and catalyst. After 3 h of stirring, the
reactants were transformed into products. The analysis of spectral data
1H NMR, 13C NMR, and MS supported the formation of isocoumarin. The
formation of the product prompted us to optimize the reaction
conditions.
To explore the generality of the applied strategy and to obtain 100%
product yield in a shorter reaction time, we attempted to investigate the
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Corresponding author.
1566-7367/© 2014 Elsevier B.V. All rights reserved.