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z Catalysis
An Efficient Phosphotungstic Acid Catalysed Synthesis of
4,5-Dioxopyrrolidines and Study of the Mechanistic Effect
of the Solvent on the Reaction
Soumyadip Basu,
[a]
Tanushree Ghosh,
[a]
Suvendu Maity,
[b]
Prasanta Ghosh,
[b]
and
Chhanda Mukhopadhyay*
[a]
An efficient protocol for the synthesis of dioxopyrrolidine
scaffolds has been established using phosphotungstic acid as
an effective catalyst in a multicomponent reaction of aromatic
primary amines, dialkyl acetylene dicarboxylates and
formaldehyde at room temperature in alcohol as a green
solvent. In this methodology, the reactant solvent has an
important part and is involved in the reaction mechanism to
increase the versatility of the product. This protocol involves
environment friendly, cost effective methodology with a
comparatively simple reaction mechanism.
Introduction
Pyrrolidines, being biologically important heterocycles, exhibit
antifungal,
[1]
antibacterial,
[2]
and most importantly anticancer
[3]
properties. Previous work that were reported
[4]
for the synthesis
of dioxopyrrolidines, generally involved higher reaction tem-
perature, longer time period or hazardous catalysts. In one of
those examples, Das and his group synthesised dioxopyrroli-
dines using HCl as catalyst.
[4c]
In addition, in another report,
they synthesized the same products using I
2
.
[4d]
Again, in few
reports, the exchange of the functional groups of the
alkynoates with the solvents was observed whereas, in some
cases, the solvent did not attach to the product. In both the
reports of Das and his group, the solvent did not take part in
the mechanism (Scheme 1). Although some previous work was
done on the synthesis of this moiety, but the difference in the
product formation concluded that detailed investigation of the
mechanism of the reaction is yet to be disclosed. We studied
the reaction in both possible ways, i. e. one in which chance of
exchange of group and the other one where no exchange is
observed. We have also tried various solvents and detected the
effect of the solvent on the reaction. This study also increases
the diversity of the synthesis of dioxopyrrolidines. In addition,
we also explained the reaction mechanism in much simpler
path than the previous reports.
Generally, heteropoly acids are oxygen acids where oxygen
atom connects heteroatomic and multiatomic molecules
through bridging ligand.
[5]
These acids normally dissolve in
small polar solvents like water, methanol, ethanol and
acetone,
[6]
but remain undissolved in non polar or macro-
molecular polar solvents. These acids have a very distinctive
acidic property, and the acidity can be adapted according to
the situation by altering the composition of the elements.
[7]
It
has strong acidic and redox properties. It also offers advantages
of stable structure, high-speed regeneration, easy loading,
noncorrosive nature, high activity, easy modification and low
pollution
[8]
and hence emerges as a type of enviro-friendly
green catalyst.
[9]
Heteropoly acid exhibits high catalytic activity
in various reactions in both liquid-solid and gas-solid systems.
One of the most widely studied heteropoly acid is phospho-
tungstic acid which has metal oxide as well as complex
structures.
[10]
Phosphotungstic acid (PTA) also, has a distinctive
“pseudo-liquid phase” nature, which allows reactions to be
taken place in both on the surface as well as inside the catalyst.
Phosphotungstic acid is strongly acidic in solids and in
solutions too, and retains a firmed Keggin structure
[11]
in both
the phases. Phosphotungstic acid has been used widely in both
homogeneous and heterogeneous reactions
[12]
because of its
strong catalytic activity, superior selectivity, low reducibility,
thermal stability and usability in mild conditions.
[13]
For all these
[a] S. Basu, T. Ghosh, Prof. C. Mukhopadhyay
Department of Chemistry, University of Calcutta, 92 APC Road, Kolkata-
700009, India
E-mail: cmukhop@yahoo.co.in
[b] Dr. S. Maity, Dr. P. Ghosh
Department of Chemistry, R. K. Mission Residential College, Narendrapur,
Kolkata 700103, India
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/slct.201901011
Scheme 1. Synthesis of 4,5-Dioxopyrrolidines.
Full Papers DOI: 10.1002/slct.201901011
5763 ChemistrySelect 2019, 4, 5763 – 5767 © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim