Fig. 3 Paal–Knorr reaction of benzylamine using magnetic nano-
FGT in water: (a) before, (b) after completion of the reaction.
Scheme 2 Nano-FGT promoted aza-Michael reactions (above) and
pyrazole synthesis (below).
out that these biphasic reactions functioned well in an aqueous
medium without the need for any phase-transfer catalyst,
which is probably due to the selective absorption of MWs
by reactants, polar nano-catalyst, and aqueous medium.10a
Separation of the catalyst and isolation of products are the
most significant aspects of aqueous organocatalysis.9 Catalyst
recovery is generally performed by filtration with reduced
efficiency and extractive isolation of products requires exces-
sive amounts of organic solvents. In our case, because of the
superparamagnetic nature of the catalyst, within a few seconds
after stirring stopped, the reaction mixture (Fig. 3(a)) turned
clear and catalyst was deposited on the magnetic bar
(Fig. 3(b)); the catalyst was easily removed using an external
magnet. In most of the experiments, we observed that after
completion of the reactions, the phase separation of the
desired product from the aqueous media occurred
(Fig. 3(b)). This facilitated isolation of crude product by
simple decantation instead of tedious extraction processes,
thus reducing the use of volatile organic solvents during
product workup. In a few cases, solid product precipitated
out; the product could then be isolated by simple filtration.
To test the lifetime and level of reusability of the catalyst, we
conducted the experiments using the recycled nano-FGT
organocatalyst for the Paal–Knorr reaction of benzylamine.
After the completion of the first reaction, the product layer
was removed by decantation and the catalyst was recovered
magnetically, washed with water and methanol, and dried.
A new reaction was then performed with fresh reactants under
similar conditions. It was observed that the developed catalyst
could be used at least five times without any change in activity.
The reaction could also be carried out simply by removing the
product layer and adding fresh benzylamine and tetrahydro-
2,5-dimethoxyfuran, and similar results were obtained.
In summary, we have developed a novel concept of nano-
organocatalyst, by supporting benign and naturally abundant
glutathione on magnetic ferrite nanoparticles. The recyclable
catalyst showed excellent activity for Paal–Knorr reaction of a
variety of amines and crucially the entire process was carried
out in aqueous medium, without using organic solvent in the
reaction as well as during the workup.
V. P. and B. B. are postgraduate research participants
at the National Risk Management Research Laboratory a
dministered by the Oak Ridge Institute for Science and
Education.
Notes and references
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In order to study the versatility of this protocol, this catalyst
was also examined for the synthesis of pyrazole and for
aza-Michael reaction (Scheme 2). Both reactions proceeded
expeditiously with excellent product yields within 20 min and
the catalyst could be reused for at least three conjugative runs.
Phase separation was observed in the case of pyrazole synth-
esis and product was isolated by simple decantation. However,
in the case of aza-Michael reaction, because of the high
solubility of the product in water due to the presence of the
free –NH group, it was extractively isolated using ethyl
acetate. The developed process opens up a benign route for
these synthetically important conversions.
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