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TABLE-1
as Calcium Channel Blockers, US Patent 7687511 (2010).
STUDY ON DEPENDENCE OF CATALYST (% w/v)
IN OVERALL REACTION YIELD
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Concentration ratio of
S. No.
Reaction yield (%)
catalyst (%)
1
2
3
4
5
6
7
8
< 1
1
2
3
5
7
10
77
85
87
91
95
90
82
76
5
6
.
.
7. S.G. Newman and K.F. Jensen, Green Chem., 15, 1456 (2013);
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170 (1992);
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1
Without catalyst
1
1
Synthesis of pyrimidine by Knoevenagel condensation:
Dihydropyrimidines and pyrimidines are known for then T-
type calcium channel blocking activity [1,2]. The pyrimidines
have become a choice class of their medicinal chemistry because
of stability towards oxidation compared to dihydropyridines.
The preferred synthetic route for pyrimidines is through
Knoevenagel condensation of an aldehyde or ketone and an
acetoester. The reaction yields decreased due to the water mole-
cule generated in the reaction is an inhibitor of the reaction. in
situ removal of water and moisture absorbing materials are
the two options [25-27], which were often observed with
minimum success and inconsistent yields [25-27]. Recent
mechanism studies had suggested that moisture was not the
real problem and the catalysts offering more surface area have
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1
1
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1
1
1
1
https://doi.org/10.1021/ja306622y.
18. A.J. Zillich, J. Garg, S. Basu, G.L. Bakris and B.L. Carter, Hypertension,
8, 219 (2006);
4
proven to be more useful [28-31]. The use of Fe
3
O
4
@SiO was
2
https://doi.org/10.1161/01.HYP.0000231552.10054.aa.
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first of its sort and near doubling of reaction yield is in expected
lines considering our similar observation with thiophenes,
terpyridine, quinazoline and isoxazole [23].
1
2
2
2
0. A. Chaudhary, P.K. Sharma, P. Verma and R. Dudhe, Anal. Univ.
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Conclusion
2-Amino-5-carboethoxy-4-hydroxypyrimidine is a useful
synthon for medicinal chemistry and we reported herein a simple
and scalable synthesis for the same. The doubling of yield has
2. H. Sheibani, M. Seifi and A. Bazgir, Catalyst Synth. Commun., 39, 1055
(
2009);
represented that Fe
3
O
4
@SiO
2
does help in improvement of
https://doi.org/10.1080/00397910802474982.
3. G.V. Shiva Reddy, M. Chandrappa, F. Rahaman, B.N. Murthy and P.K.
Pullela, Asian J. Chem., 29, 124 (2017);
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Heterocycl. Commun., 17, 129 (2011);
2
2
reaction yields of heterocyclics. The Knoevenagel condensation
was reported to be a low yielding reaction [32,33] and we found
a practical and mild way to improve the reaction yield. The
Fe
3
O
4
@SiO particles are about 40 nm size and the size of the
2
https://doi.org/10.1515/hc.2011.025.
particles does play a role in reaction improvement. The optimum
catalytic ratio was about 5 % (w/v) and using less than 1 % (w/v)
results in reactions yields of uncatalyzed reactions. The marginal
decrease reaction yield at 7-10 % (w/v) catalyst needs further
study and in situ decomposition of product at higher catalytic
concentration needs be understood in future studies.
2
2
2
2
2
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ACKNOWLEDGEMENTS
This study is partially supported by a grant for Dr. Phani
Kumar Pullela, with VGST/SMYSR/GRD-444/2014-2015
from Vision group on Science and Technology, Government
of Karnataka, India under the Seed Money forYoung Scientific
Researchers (SMYSR) scheme.
3
3
1. R.K. Sharma, S. Sharma, S. Dutta, R. Zboril and M.B. Gawande, Green
Chem., 17, 3207 (2015);
https://doi.org/10.1039/C5GC00381D.
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