Scandium(III) triflate-catalyzed efficient synthesis of substituted 1-pyridylimidazo-[1,5-a]-pyridines

Article abstract of DOI:10.1080/00397910902788158

An efficient synthesis of substituted 1-pyridylimidazo-[1,5-a]-pyridines has been accomplished using scandium(III) triflate as catalyst under mild conditions in excellent yields.

Full text of DOI:10.1080/00397910902788158

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Scandium(III) Triflate–Catalyzed
Efficient Synthesis of
Substituted 1-Pyridylimidazo-
[1,5-a]-pyridines
Shrinivas S. Kottawar a , Shaphi A. Siddiqui a , Vishal
P. Chavan a , Wamanrao N. Jadhav a & Sudhakar R.
Bhusare a
a Department of Chemistry, Dnyanopasak College,
Parbhani, India
Published online: 04 Sep 2009.
To cite this article: Shrinivas S. Kottawar , Shaphi A. Siddiqui , Vishal P. Chavan ,
Wamanrao N. Jadhav & Sudhakar R. Bhusare (2009): Scandium(III) Triflate–Catalyzed
Efficient Synthesis of Substituted 1-Pyridylimidazo-[1,5-a]-pyridines, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:19, 3546-3549
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Synthetic Communications1, 39: 3546–3549, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902788158
Scandium(III) Triflate–Catalyzed Efficient
Synthesis of Substituted
1-Pyridylimidazo-[1,5-a]-pyridines
Shrinivas S. Kottawar, Shaphi A. Siddiqui, Vishal P. Chavan,
Wamanrao N. Jadhav, and Sudhakar R. Bhusare
Department of Chemistry, Dnyanopasak College, Parbhani, India
Abstract: An efficient synthesis of substituted 1-pyridylimidazo-[1,5-a]-pyridines
has been accomplished using scandium(III) triflate as catalyst under mild
conditions in excellent yields.
Keywords: Ammonium chloride, 1,2-dipyridyl ketone, Lewis acid, 1-pyridylimidazo-
[1,5-a]-pyridines, scandium(III) triflate
INTRODUCTION
The synthesis of imidazo-[1,5-a]-pyridines mainly involves the acylation
reaction of 2-aminomethylpyridine, followed by cyclization with phos-
phorus oxychloride or polyphosphoric acid[1] or thioacylation followed
by ring closure using dicyclohexylcarbodiimide (DCC) or mercuric
salts.[2] Other approaches include use of 2-cyanopyridine by the Vilsmeier
reaction[3] or by oxidization reaction of Schiff bases in the presence of
molecular sieves or metal ions, requiring two to three steps from the
dipyridyl ketone.[4–8] The synthetic protocols for 1-pyridylimidazo-[1,5-
a]-pyridines reported so far suffer from one or more disadvantages, such
as harsh reaction conditions, poor yields, longer reaction times, and the
use of hazardous reagents and often expensive acid catalysts. In addition,
Received November 3, 2008.
Address correspondence to Sudhakar R. Bhusare, Department of Chemistry
Dnyanopasak College, Parbhani 431401, India. E-mail: bhusare71@yahoo.com
3546

1-Pyridylimidazo-[1,5-a]-pyridines
3547
Scheme 1. Synthesis of 1-pyridylimidazo-[1,5-a]-pyridines catalyzed by scandium(III)
triflate.
a method based on a reaction strategy using room temperature acidic
ionic liquid [HBIM]-BF4 has been reported.[9] Moreover, the synthesis
of these heterocycles has been carried out in dimethylformamide
(DMF), dimethylsulfoxide (DMSO), and acetic acid, leading to complex
isolation and recovery procedures. Therefore, the development of facile
and environmentally friendly methods for the synthesis of 1-
pyridylimidazo-[1,5-a]-pyridines is a necessary part of organic synthesis.
The present protocol is not only simple and high-yielding but also
decreases environmental pollution. At the onset of this work, we have
investigated a variety of reaction conditions with the model reaction
using metal triflates as catalyst (Table 1).
Initially, a systematic study was carried out to find the best molar
concentration of catalyst scandium(III) triflate for the synthesis of
1-pyridylimidazo-[1,5-a]-pyridine derivatives; the reaction of 1,2-dipyridyl
ketone, benzaldehyde, and ammonium acetate was carried out in either
in the absence of catalyst or in the presence of various solvents under
different conditions (Table 1). As shown, the best yield was achieved when
5 mol% catalyst used in ethanol as solvent (Table 1, entry 6).
Table 1. Synthesis of 3a under different reaction conditions
Sc(OTf)3
(mol%)
Time
(h)
Temp.
(ꢀC)
Isolated
yield (%)
Entry
Solvent
1
2
3
4
5
6
7
8
9
Dichloromethane
Acetonitrile
Acetonitrile
Methanol
Methanol
Ethanol
Ethanol
Ethanol
Ethanol
5
5
5
5
5
5
0
1
2
12
12
1
12
1.5
0.5
12
12
12
30
RT
Reflux
RT
Reflux
Reflux
Reflux
Reflux
Reflux
20
15
80
Traces
85
93
00
20
55

3548
S. S. Kottawar et al.
Table 2. Synthesis of 1-pyridylimidazo-[1,5-a]-pyridines
Reaction
Isolated
time (min) yield (%)a
Entry
Ar-CHO
a
b
c
d
e
f
g
h
i
C6H5-CHO
30
30
40
40
35
50
35
50
60
40
93
91
90
87
91
89
88
92
80
94
4-OCH3-C6H4-CHO
2-OH-C6H4-CHO
4-OH-C6H4-CHO
3-OH-C6H4-CHO
2-Cl-C6H4-CHO
4-CH3-C6H4-CHO
3-OCH3-4-OH-C6H3-CHO
4-NO2-C6H4-CHO
4-OH-3,5-di-tert-but-C6H2-CHO
j
aAll of the products were characterized by spectral and physical
data.
Encouraged by this success, we extended the methodology to a variety
of aromatic aldehydes, which are summarized in Table 2. This method is
effective for the preparation of 1-pyridylimidazo-[1,5-a]-pyridines 3a–j from
both electron-rich as well as electron-deficient aromatic aldehydes. The aryl
groups substituted with different groups and also the same groups located at
different positions of the aromatic ring did not show any marginal effect on
the formation of 1-pyridylimidazo-[1,5-a]-pyridines 3. Another advantage of
this methodology is a nearly stiochiometric amount of ammonium acetate
was used in the course of the reaction, whereas previously many-fold ammo-
nium acetate was required. This is an additional advantage of the novel
methodology.
In conclusion, we describe a mild and efficient method for the synthesis
of 1-pyridylimidazo-[1,5-a]-pyridines using scandium(III) triflate as a
novel Lewis acid catalyst. This method is not only provides an excellent
complement to 1-pyridylimidazo-[1,5-a]-pyridines synthesis but also avoids
the use of hazardous acids or bases and harsh reaction conditions. The
advantages of this method include good substrate generality, the use of
inexpensive reagents and catalyst, mild conditions, and operational ease.
GENERAL EXPERIMENTAL PROCEDURE
A mixture of 1,2-dipyridyl ketone (10 mmol), aromatic aldehyde
(10 mmol), ammonium acetate (20 mmol), and scandium(III) triflate
(5 mol%) in ethanol (10 ml) was stirred at 75 ꢀC for the appropriate time
(Table 2), and the completion of reaction was monitored by thin-layer

1-Pyridylimidazo-[1,5-a]-pyridines
3549
chromatography (TLC). After completion, the reaction mixture was
treated with aqueous sodium bisulfate. The separated solids were filtered,
washed with water, and dried. The crude products obtained were purified
by column chromatography on silica gel (60–120 mesh size) using 25%
ethyl acetate in petroleum ether as eluent.
ACKNOWLEDGMENTS
We acknowledge Dr. P. L. More, Principal. Dnyanopasak College,
Parbhani, for providing necessary facilities and UGC, New Delhi, for
financial support (MRP-47-125/06).
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