CuO-CuAl2O4 and d-glucose catalyzed synthesis of a family of excited state intramolecular proton transfer imidazo[1,2-a]pyridine analogues and their optical properties

Article abstract of DOI:10.1016/j.dyepig.2015.05.014

A simple and efficient route to luminescent imidazo[1,2-a]pyridines from 2-aminopyridines, phenylacetylene and arylaldehydes was achieved by an one-pot, tandem process starting with an A3-coupling followed by 5-exo-dig cyclization. Copper(II)oxide/copper

Full text of DOI:10.1016/j.dyepig.2015.05.014

Accepted Manuscript
CuO-CuAl O and D-Glucose Catalyzed Synthesis of a Family of Exited State
2
4
Intramolecular Proton Transfer Imidazo[1,2-a]pyridine Analogues and their Optical
Properties
Umamahesh Balijapalli, Sathiyanarayanan Kulathu Iyer
PII:
S0143-7208(15)00185-0
10.1016/j.dyepig.2015.05.014
DYPI 4777
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 20 March 2015
Revised Date: 8 May 2015
Accepted Date: 11 May 2015
Please cite this article as: Balijapalli U, Iyer SK, CuO-CuAl O and D-Glucose Catalyzed Synthesis of a
2
4
Family of Exited State Intramolecular Proton Transfer Imidazo[1,2-a]pyridine Analogues and their Optical
Properties, Dyes and Pigments (2015), doi: 10.1016/j.dyepig.2015.05.014.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
CuO-CuAl O and D-Glucose Catalyzed Synthesis of a Family of Exited State
2
4
Intramolecular Proton Transfer Imidazo[1,2-a]pyridine Analogues and their
Optical Properties
Umamahesh Balijapalli and Sathiyanarayanan Kulathu Iyer *
Chemistry Division, School of Advanced sciences, Vellore Institute of Technology, Vellore-
6
32014, Tamilnadu, India. E-mail: sathiya_kuna@hotmail.com
Graphical abstract

ACCEPTED MANUSCRIPT
Abstract
A simple and efficient route to luminescent imidazo[1,2-a]pyridines from 2-aminopyridines,
phenylacetylene and arylaldehydes was achieved by an one-pot, tandem process starting with an
A3-coupling followed by 5-exo-dig cyclization. Copper(II)oxide/copper aluminate composite (5
2 4
wt% CuO-CuAl O composite) and D-glucose catalyzed optimal conditions for the reaction were
established after examining various reaction parameters such as solvent, catalyst and
temperature. The synthesis was much compatible with various functionalities. 2-Aryl-
imidazo[1,2-a]pyridines not capable of excited state intramolecular proton transfer emission
displayed moderate fluorescence quantum yields in the blue-green region due to intramolecular
charge transfer process. In addition, they exhibited peculiar solvatochromic behavior in
chlorinated solvents like chloroform and dichloromethane. Products containing 2-(2′-
hydroxyphenyl) substituent underwent excited state intramolecular proton transfer in non polar
and polar-aprotic solvents. Although such type of emission in solvents was very weak, the Stokes
−
1
shifts values were high (14638-11448cm ) with strong solid-state emission in green to yellow
region.
1
.Introduction
Imidazo[1,2-a]pyridine based scaffold versatility in second heterocyclic ring has gained immense
attention because of its primitive subunit in many natural products and biologically active
compounds with a wide range of pharmaceutical activities [1-5]. These classes of heterocycles
are represented in day-to-day life in drugs such as zolimidine (i) (antiulcer), zolpidem (ii)
(hypnotic), and necopidem, saripidem, alpidem (iii) (anxiolytic) (Chart.1) [6-8]. On the other

ACCEPTED MANUSCRIPT
hand, in recent times, there has been a growing interest in the use of N-fused imidazoles,
particularly imidazo[1,2-a]pyridine, in the field of materials chemistry. Indeed, the distinct
excited state photophysical properties of such compounds could serve as hosts for organic
electroluminescent (EL) devices and organic light emitting diodes (OLEDs) [9-15]. Recently, D-
A type fluorophores based on imidazo[1,2-a]pyridine as the core and 4,5-diphenyl-1H-imidazole
and diphenylamine as the peripheral moieties had been developed, and photophysical,
electrochemical studies were performed. In addition, the electroluminescence (EL) properties
were explored using these compounds as the emitting layer in OLEDs [16]. Organic white
luminescent materials were fabricated using a mixture of protontransfer and nonproton-transfer
fluorophores such as 2’-methoxy and 2’-hydroxy derivatives of 2-phenylimidazo[1,2-
a]pyridines. They have similar absorption properties. However, they exhibit different
luminescence properties which ascribe to the normal (∼420 nm) and excited-state intramolecular
proton transfer processes (∼530 nm) in the solid state [17-18].
Multicomponent reactions (MCRs) of aldehyde with amine and alkyne (A3-coupling) synthesis
of propargyl amine and subsequent imidazo[1,2-a]pyridines has gained importance in organic
synthesis. Its incorporation in cascade processes of tethered cyclization with activation of triple
bond in propargyl amine followed by exo-dig cyclization affords access to versatile molecular
complex compounds [19-20]. Consequently, diverse synthetic methods were developed for the
synthesis of imidazo[1,2-a]pyridine scaffolds. Of these, the three component cascade coupling
(3CCC) of 2-aminopyridine, aldehyde and alkyne is one of the most fascinating methods for the
synthesis of imidazo[1,2-a]pyridines (Scheme 1). Typically, transition metal salts such as Ag(I),
Au(III), In(III) and Cu(II) in combination with either p-TSA/base/reducing agent or copper(I)
complex have been employed to accomplish this three-component coupling for the synthesis of

ACCEPTED MANUSCRIPT
imidazo[1,2-a]pyridines [21-25]. The synthesis of these scaffolds has been fortunately
accomplished with the use of a mixture of catalytic species such as CuCl/Cu(OTf)2
[
Cu(I)−Cu(II)], InBr /Et N, CuI/NaHSO −SiO , CuSO /p–TsOH, CuCl/ZnCl2 and
3 3 4 2 4
CuSO 5H O/Glucose [Cu(I) −Cu(II)]. Recently, the strategic use of this approach with copper
4
.
2
containing metal-organic frameworks (MOFs) [Cu(BDC)] as reusable catalysts has been
documented for the multicomponent synthesis of imidazo[1,2-a]pyridines [26-29]. However, the
developments of catalyst with tunable catalytic activity and organic synthesis catalyzed by
metal/metal oxide nanoparticles have received much significance in both academia and industry.
In comparison with other transition metals extensively used, copper-based catalysts are cheap,
non-toxic, environmental friendly and abundant. In the past decades, various copper salts were
applied as Lewis acids in homogeneous catalysis and different catalytically active copper
complexes were also reported [30]. Very few reports are found for multicomponent organic
synthesis catalyzed by copper(II) oxide /copper(II) aluminat composite. Because of the efficient
biological activities and significant photophysical properties of these scaffolds, we attempted to
synthesize MCRs by employing copper(II) oxide /copper(II) aluminate composite as catalyst.
Scheme 1. Generalized route for the synthesis of N-fused pyridines by a cascade approach.
Although these methods are very useful for the synthesis of N-fused derivatives, these classical
reactions have significant drawbacks such as sparse availability of the starting materials,
multistep synthetic operations, functional group compatibility, anaerobic procedure, use of basic

ACCEPTED MANUSCRIPT
and harsh reaction conditions, prolonged reaction time and low yields which limit their scope
[31-32]. To overcome these limitations, various new and efficient strategies such as
multicomponent coupling and transition metal catalyzed reactions have been recently developed.
In this context, three-component coupling reactions for the synthesis of N-fused pyridines
catalyzed by CuO/CuAl O composite and D-Glucose have received much attention. To the best
2
4
of our knowledge, there are no reports on three-component, one-pot syntheses of ESIPT
exhibited imidazo[1,2-a]pyridines by this MCRs.
2
2
. Results and discussion
.1 Synthesis and optimization of catalyst
2 4
The catalytic activity of copperoxide-copper(II)aluminate composite (CuO-CuAl O ) was
investigated for the synthesis of imidazo[1,2-a]pyridines using MCR approach. For a model
reaction, the reaction between benzaldehyde, phenylacetylene and 2-aminopyridine was chosen
at room temperature or reflux conditions in the presence of various solvents (Table 1). Initially,
various Cu(I) based catalysts such as CuCl, CuBr and CuI were employed. The yields obtained
were low (Table 1, entry 1-3). Similarly, Cu(II) based catalysts such as CuSO , and Cu(OAc)
4
2
were also employed, and no improvement in yields were observed (Table 1, entry 4-5). Nano
copper oxides such as CuO, Cu O and CuAl were also employed as catalyst, but little
improvement in yields were obtained (Table 1, entry 6-8). When CuO-CuAl was used as a
2
2 4
O
2
O
4
catalyst in the presence of various organic co-catalysts along with the main product, side
products were also obtained with moderate yields (Table 1, entry 9-11). The low yields and the
formation of side products could be due to the low catalytic activity of the catalyst. Interestingly,
the use of mixed nano CuO-CuAl O /D-Glucose catalytic system significantly influenced the
2
4

ACCEPTED MANUSCRIPT
selectivity and good yields were obtained (Table 1, entry 12-16). We found that 15 mol% CuO-
CuAl O and 30 mol% D-Glucose were effective for this cascade reaction. With this effective
2
4
catalyst in hand, a series of experiments were performed by varying solvents to arrive at the best
optimal reaction condition, and the results are summarised in Table 1. In search for a best
solvent, the reaction was performed in water, CH CN, DMF, THF, EtOH, DMF, EtOAc, DMSO,
3
dioxane and toluene (entries 16–25). Delightfully, we found that the reaction in toluene at reflux
conditions furnished the maximum yield of the product (88%) in 18h (entry 13), and hence all
the subsequent experiments were performed in this medium.
Scheme 2. Synthesis of imidazo[1,2-a]pyridines under optimized reaction conditions.
NH2
CHO
1
3
5 mol % CuO-CuAl O
0 mol % D-Glucose
2
4
+
+
R2
N
N
Y
R1
R2
Toluene,
N
R1
24h, Reflux
1a
3
2a
Y
4, 5

ACCEPTED MANUSCRIPT
This generalized synthetic protocol is of particular interest because of excellent photophysical
properties in solid and solution state known to be used in fluorescence sensors and
optoelectronics. It provides therapeutically important compounds. With optimized conditions, the
scope and limitations of this cascade reaction were finally examined, and the results are
summarized in Scheme 2. In most cases of aromatic aldehydes and aminopyridines, the three-
component reaction proceeded smoothly under these experimental conditions, and the
corresponding products were obtained in moderate to good yields (41–89%). Various aromatic
aldehydes and aminopyridines afforded good to high yields, and these conditions were

ACCEPTED MANUSCRIPT
compatible with various functional groups. A variety of functional groups such as halogen,
dimethylamino, methoxy and methyl groups substituted at the aromatic ring of the aldehyde and
aminopyridine substrates were tolerated. The presence of heavy atom like bromine substituent on
either aldehyde or aminopyridine such as 5d, 5h, 5i, 5j and 5k allowed the reaction to continue
moderately and yields of 68, 41, 61, 45 and 49 % respectively were obtained. The synthesized
1
13
structures were identified by FTIR, H, C NMR and HRMS analysis. Single crystal of 5d was
grown by slow evaporation of ethanol and tetrahydrofuran mixture of compound 5d at room
temperature. This was confirmed by single crystal X-ray studies. The X-ray crystal structure of
compound 5d is given in Fig 1. Significant intermolecular CH-π interactions were found to exist
along the crystallographic axis direction with different intermolecular distance of CH-π...O (2.41
Å) and O-H...N (1.80 Å). The intermolecular π-π interactions linked the neighbouring molecules,
which resulted in the formation of dimers. The CH-π interactions are known to cause
fluorescence quenching in the solid state [33]. Surprisingly, despite the existence of π-π
networks, compounds exhibited strong green fluorescence in the solid state.
Mechanistically, the reaction is expected to proceed via in situ formation of an imine
from an aldehyde and 2-aminopyridine. This follows the addition of alkyne, after activation by
glucose through CuO(II)/Cu O(I) results in the formation of the A3 coupled propargylamine.
2
Tautamerization of propargylamine followed by 5-exo-dig cyclization formed product which
finally isomerize to final product 4.
2
.2. Photophysical properties
The spectral properties of the imidazo[1,2-a]pyridine derivatives 4a-4d, 5a-5k such as
absorption(λmax), emission(λ ), Stokes shift and molar extinction coefficient(ε) measured in
em

ACCEPTED MANUSCRIPT
chloroform solvent are summarized in Table 2. All the compounds showed absorption maximum
with wavelength ranging from 245 to 360 nm. Most of the derivatives displayed two absorption
maxima with highest energy absorption band I in the region of 280 to 300 nm and lowest energy
absorption band II in the region of 305 to 360 nm. The lowest energy transition band II could be
attributed to the transition from singlet ground (S ) to the first excited state (S ) S →S . A
0
1
0
1
systematic trend in absorption spectra was not obeyed in chloroform solvent even though there
was opportunity for ESIPT and non-ESIPT modes in this library. However, ESIPT compatible
derivatives displayed marginally red shifted absorbance maxima in toluene, tetrahydrofuran,
acetonitrile when compared to non-ESIPT adaptable derivatives. From Fig 2, it is evident that the
absorption properties of these derivatives experienced peculiar behavior in chlorinated solvents
like chloroform. Relative to other solvents such as toluene, THF and acetonitrile there were large
hypsochromic shifts in the low energy absorption spectra of the dyes except in 4d, and their
absorption maxima were observed in the range of 305−360nm. Distinctly, dye 4d experienced
more bathochromically shifted absorption maxima of 360 nm in chloroform compared to other
dyes either in chloroform or even in different solvents (λA(Tol)-345, λA(THF)-335, λA(ACNl)-337nm).
Predominantly, red shifted low energy maxima for all the derivatives were observed in non polar
toluene compared to other solvents with exception of 4d.
-1
Large Stokes shift values of 5231-6318 cm were observed for non ESIPT derivatives 4a-4d in
chloroform ascribed to intramolecular charge transfer [34] from phenyl to imidazo[1,2-
-1
a]pyridine. Among 4a-4d, dye 4d have large Stokes shift value of 6318 cm and were more
-1
pronounced at 7598 cm in polar acetonitrile solvent which could be attributed to increase
intramolecular charge transfer between dimethylamino group to imidazo[1,2-a]pyridine. Typical
-1
ESIPT derivatives 5a-5c, 5h-5k showed very large Stokes shift values of 12399-14638 cm in

ACCEPTED MANUSCRIPT
-1
chloroform. However, among the ESIPT derivatives, the largest Stokes shift value of 14638 cm
-1
was exhibited by 5b in chloroform, and lower value of 11448 cm was observed for 5d in non
polar toluene. Further, the large emission shift from absorption maxima along with dual emission
might be due to the presence of –OH group in phenyl ring connected to a imidazo[1,2-a]pyridine
nd
ring at 2 position through intervening π-conjugation, probably inducing the excited state
intramolecular proton transfer character which would also be responsible for the observed larger
Stokes shift values as the characterstic features of ESIPT mechanism [35-41].
The emission properties of 4a-4d, 5a-5d were studied in different solvents, and the data are
summarized in Table 2. From Fig 3, it can be concluded that the emission maxima of
imidazo[1,2-a]pyridines 4a-4c was not significantly affected by solvent polarity. On the other
hand, a slightly blue shifted emission for 4a, 4b and 4c (21, 10, 21 nm respectively) was
observed in chloroform compared to its emission in toluene. The emission wavelength of
dialkylamino substituted imidazo[1,2-a]pyridine 4d was significantly affected by solvent polarity
(e.g., 409 nm in toluene, 419 nm in THF and 453 nm in acetonitrile) showing a considerable
degree of charge-transfer character in its excited states. According to the expectation, the
bathochromic shift of absorption in chlorinated solvents significantly enhances the charge-
transfer character in 4d when going from simple derivatives of imidazo[1,2-a]pyridine to the
dialkylamino substituted analogue (Table 2, Fig 3). By virtue of the effect of chlorinated solvents
on absorption of 4d, more pronounced and bathochromically shifted emission was obsreved in
DCM (481 nm) and chloroform (466 nm) compared to polar acetonitrile (453 nm) shown in
Table 3.
Relative to non-ESIPT imidazo[1,2-a]pyridine 4a (entry 1), there were large bathochromic shifts
in the emission spectra of new ESIPT imidazo[1,2-a]pyridines 5a-5k (Fig 4); their ESIPT

ACCEPTED MANUSCRIPT
emission maxima were observed within the range of 539-573 nm along with normal emission in
the range 384-414 nm. In contrast to unsubstituted hydroxy phenyl imidazo[1,2-a]pyridine 5a,
methoxy substitution on phenyl ring containing hydroxy phenyl imidazo[1,2-a]pyridine 5e-5g
doesn’t undewent ESIPT process and exhibited only normal fluorescence in solvents. Dyes 5a-
5
c, 5h-5k exhibited two emission maxima, among which one was the lower energy maxima
attributed to ESIPT and the other was the higher energy band of normal emission. In general,
ESIPT process took the lead in non polar solvents such as toluene and weakened in polar
solvents. Further, to understand the effect of chlorinated solvents on ESIPT emission, we
measured emission of 5a-5d in various solvents and the data is summarized in Table 3.
Unsubstituted dye 5a showed dual emission in all the solvents except in dichloromethane. In
rd
addition, the presence of methyl group at 3 position on imidazo[1,2-a]pyridine 5b
predominantly showed dual emission, which was assigned to ESIPT emission along with normal
th
emission. On the other hand, the presence of bromine group at 5 position led 5d to emit in
higher energy region, especially in the blue region. The presence of two bromine substituents in
5
h was expected to exhibit blue shift emission in toluene; on the contrary, it exhibited more red
shift ESIPT emission of 588 nm in the library. This unexpected behaviour arose due to the
increased charge transfer from bulky bromine atom to imidazo[1,2-a]pyridine ring. Compounds
4
a-4d were strongly fluorescent with moderate quantum yields (Φ ) of 0.34−0.13, which were
f
much greater than that of imidazo[1,2-a]pyridine 5a (Φ = 0.03). Further, to gain information
f
about the excited state processes, the fluorescence lifetime of imidazo[1,2-a]pyridines was
measured by the time correlated single photon counting method. This was done by exciting the
sample at 295 nm, 150 ps pulse using Nanoleds. The decay profiles of imidazo[1,2-a]pyridines
derivatives 4a-4d dissolved in chloroform are given in Fig 5. The decay profiles could be fitted

ACCEPTED MANUSCRIPT
with single exponential function, and the lifetime data are summarized in Table 2. The
fluorescence lifetime of 4a, 4b, 4c and 4d were measured to be 1.73, 1.15, 1.56, 3.13 ns
respectively. In general, the fluorescence lifetimes of 2-substituted compounds were smaller;
however, no life time values were obtained for ESIPT derivatives. The low quantum yields and
undetectable life time values for imidazo[1,2-a]pyridine 5a-5k suggest the existence of very
weak excited state intramolecular proton transfer of their 2’-hydroxyaryl substituents.
2
.3. Solid state fluorescent properties
2
’-hydroxyphenyl imidazo[1,2-a]pyridine derivatives were strongly emissive in the solid state
due to ESIPT process dependent on the structure of polymorphs which was accompanied by a
large Stokes shift [9,42]. Indeed, in solid state, the absence of solvent interactions leads to ESIPT
active capable zwitter ionic keto form shown in Fig 6, and is hence strongly emissive [43-44]. In
addition, there is short intramolecular O-H…N and CH-π…O contacts which stabilize the
structure, and probably leads to increased intensity of fluorescence in solid state. We performed
solid-state emission measurements for 5a-5k, and the emission maxima were in the range of
5
07−556 nm, as given in Fig 7. In general, ESIPT compatible derivatives such as 5a-5c, 5h-5k
exhibited blue shifted solid state emission by 40, 76, 45, 17, 32, 32, 31 nm respectively when
compared to their respective ESIPT emission in chloroform solvent. Due to the absence of
ESIPT emission in chloroform solution, compounds 5d-5g showed large red shifted emission by
1
36, 160, 141, 157 nm respectively in solid state. Interestingly, for dyes 5d (550 nm) and 5h
(556 nm) containing bromine atom on imidazo[1,2-a]pyridine, the solid ESIPT emission was
more pronounced and red shifted compared to dye 5a (521 nm). A similar trend was observed in
imidazo[1,2-a]pyridines 5e (547 nm), 5f (537 nm), 5g (540 nm) containing electron donating
groups on phenyl ring in which noticeable red shifted emission of 26, 16, 19 nm was observed.

ACCEPTED MANUSCRIPT
Distinctly, emission of the compounds 5b-5c (508, 509 nm), 5j-5k (507, 520 nm) which were
marginally blue shifted to that of dye 5a having electron rich methyl groups on imidazo[1,2-
a]pyridine moiety. Further, non-ESIPT imidazo[1,2-a]pyridines also displayed luminescence in
the solid state; however, emission was weak and hypsochromically shifted (Table 2). From the
solid state emission measurements, it is clear that 4a-4d having two emission maxima were in
the range of 388−460 nm. Compounds 4a, 4b, 4c were red shifted by 19, 44, 34 nm respectively
when compared to emission in chloroform with exception of 4d which was slightly blue shifted
by 6 nm whose emission was broadly distributed in the wide range of 375 to 605 nm in emission
area. Hence, it can be inferred that the increased fluorescence intensity in the solid state qualified
them for applications in solid state lightening materials like OLEDs, lasers and fluorescence
probes.
3
. Conclusions
In summary, a simple and efficient route to a luminescent imidazo[1,2-a]pyridines from 2-
aminopyridines, phenylacetylene and aromatic aldehydes were achieved by an one-pot, tandem
process using copper(II) oxide-copper(II) aluminate composite and D-glucose. 2-Aryl-
imidazo[1,2-a]pyridines not capable of ESIPT emission displayed moderate fluorescence
quantum yields and high Stokes shift values. In addition, they exhibited significant charge
transfer behavior in chlorinated solvents i.e., in 4d, and a higher bathochromically shifted
emission was obsreved in DCM (481 nm) and chloroform (466 nm) compared to polar
acetonitrile (453 nm). Products containing 2-(2′-hydroxyphenyl) substituents underwent a weak
ESIPT process in non polar and polar aprotic solvents with larger Stokes shifts values of 14638-
−
1
1
1448 cm . However, ESIPT process was more pronounced in solid state which resulted in the
display of a strong, solid-state emission in green to yellow region. The short intramolecular O-

ACCEPTED MANUSCRIPT
H…N and CH-π…O interactions stabilized the zwitter ionic structure, probably leading to
increased fluorescence intensity in its solid state which is a desired factor for solid state
lightening materials like OLEDs and lasers.
4
4
. Experimental section
.1. General information
All organic chemicals and solvents were purchased from Sigma Aldrich, SDFine and AVRA
1
13
chemicals and were used directly without further purification. H and C NMR spectra were
taken on Bruker 400 MHz using CDCl as solvent with TMS as an internal standard. Melting
3
points were measured on Microprocessor based melting point apparatus and were not corrected.
HRMS values were obtained on Joel GCMate II GC-Mass Spectrometer. FTIR spectra of the
synthesized organic compounds were recorded using a Jasco-4100 spectrometer instrument. UV-
visible spectra were taken using Hitachi U-2910 spectrophotometer. Fluorescence spectra in
solution and solid states were measured using Hitachi F-7000 fluorescence spectrometer. The
fluorescence quantum yields (Φ ) were measured with quinine sulfate (Φ ) 0.55 in 1N H SO
f
f
2
4
solution as a standard, λ = 366 nm. Analytical thin-layer chromatography (TLC) was performed
ex
on pre-coated plates (Merck, silica gel 60 F254). Silica gel (60-120 mesh) was used for column
chromatography. Single crystal X–ray diffraction data were taken on bruker kappa APEXII. The
structures were solved by direct methods.
4
.2. General procedure for the preparation of copper(II)oxide-copper(II)aluminate
composite.

ACCEPTED MANUSCRIPT
0
.1 g of Cu(NO
3
)
2
.3H
2
2 4
O was dissolved in 10 ml of distilled water. 2 g of CuAl O was
disperssed in the abov solution. The solid mass was obtained after heating the suspension at 80°
C, which was later calcinated at 300° C for 6 h to obtain 5 Wt% CuO-CuAl O composite.
2
4
4
.3. General procedure for the preparation of compound 4a-d, 5a-k.
A mixture of substituted benzaldehydes or substituted salicyladehydes (3) (10 mmol), 2-
aminopyridine (1) (10 mmol) were taken in a 100 mL round bottom flask containing 10 mL dry
toluene at room temperature, sealed and warmed for 5min until the dissolution of the solid
contents. After bringing the reaction mixture to room temperature, 15 mol% CuAl O , 30 mol%
2
4
D-Glucose and phenylacetylene (2) (13 mmol) were added and the reaction mixture was refluxed
for 24h. The completion of the reaction was monitored by TLC; the resulting product was
purified by column chromatography over silica gel (60-120 mesh) using n-hexane and ethyl
acetate mixture (9:1) as eluent to obtain the compounds (4a-d, 5a-k). Thus obtained solid was
further purified by recrystallizing in 1:1 ethanol and tetrahydrofuran mixture.
0
3
-benzyl-2-phenylimidazo[1,2-a]pyridine (4a): White solid; Melting point: 153-155 C; IR
(
KBr): 3074, 3007, 2924, 2848, 1629, 1602, 1489, 1394, 1352, 1255, 1170, 1126, 962, 769, 748,
-
1 1
7
4
=
27, 694, 677, 619, 555 cm ; H NMR (400 MHz, CDCl ) δ ppm: 4.53 (s, 2H), 6.73-6.71 (t, J =
3
.0 Hz, 1H), 7.16-7.18 (d, J = 8.0 Hz, 2H), 7.23-7.19 (m, 1H), 7.40-7.29 (m, 4H), 7.48-7.44 (t, J
1
3
8.0 Hz, 2H), 7.71-7.70 (d, J = 4.0 Hz, 1H), 7.73 (s, 1H), 7.82-7.80 (d, J = 8.0 Hz, 2H); C
NMR (100 MHz, CDCl
3
) δ ppm: 30.0, 112.3, 117.6, 117.8, 123.5, 124.3, 127.0, 127.8, 127.8,
+
1
2
28.3, 128.7, 129.1, 134.6, 136.9, 144.2, 145.0; HRMS for C H N Calculated [M ] m/z
2
7
21
84.1313, Found 284.1313.

ACCEPTED MANUSCRIPT
3
-benzyl-2-(4-chlorophenyl)imidazo[1,2-a]pyridine (4b): White solid: Melting point: 140-142
0
C; IR (KBr): 3082, 3011, 3003, 2949, 2336, 1946, 1880, 1633, 1600, 1525, 1492, 1483, 1440,
-1
1
1
357, 1246, 1180, 1089, 1074, 1029, 1010, 943, 848, 821, 729 cm ; H NMR (400 MHz,
CDCl ) δ ppm: 4.46 (s, 2H), 6.73-6.70 (t, J = 6.0 Hz, 1H), 7.13-7.11 (d, J = 8.0 Hz, 2H), 7.21-
3
13
7
.17 (t, J = 8.0 Hz, 1H), 7.32-7.23 (m, 3H), 7.40-7.38 (d, J = 8.0 Hz, 2H), 7.72-7.66 (m, 4H); C
NMR (100 MHz, CDCl ) δ ppm: 29.8, 112.4, 117.6, 117.8, 123.4, 124.4, 127.0, 127.6, 128.8,
3
+
1
3
29.1, 129.4, 133.0, 133.7, 136.5, 143.0, 144.9; HRMS for C27
18.0924, Found 318.0921.
H
21N Calculated [M ] m/z
0
3
-benzyl-2-(p-tolyl)imidazo[1,2-a]pyridine (4c): Pale yellow solid; Melting point: 158-160 C;
IR (KBr): 3024, 2916, 2879, 2328, 1737, 1632, 1622, 1571, 1490, 1392, 1354, 1255, 1143, 1105,
-
1 1
1
6
7
1
028, 825, 748, 725, 694 cm ; H NMR (400 MHz, CDCl ) δ ppm: 2.41(s, 3H), 4.51 (s, 2H),
3
.74-6.70 (t, J = 8.0 Hz, 1H), 7.21-7.16 (m, 3H), 7.29-7.26 (m, 3H), 7.35-7.31 (m, 2H), 7.72-
13
3
.70 (d, J = 8.0 Hz, 4H); C NMR (100 MHz, CDCl ) δ ppm: 21.2, 29.9, 112.0, 117.4, 117.5,
23.3, 124.0, 126.8, 127.7, 128.1, 129.0, 129.3, 131.6, 136.9, 137.5, 144.2, 144.8; HRMS for
+
C
27
H
21N Calculated [M ] m/z 298.1470, Found 298.1479.
4
-(3-benzylimidazo[1,2-a]pyridin-2-yl)-N,N-dimethylaniline (4d): Orange solid; Melting
0
point: 248-250 C; IR (KBr): 3111, 3074, 3026, 2846, 2800, 2335, 1737, 1614, 1490, 1392,
-1 1
1
352, 1228, 1195, 1166, 1060, 1002, 894, 825, 727, 696 cm ; H NMR (400 MHz, CDCl ) δ
3
ppm: 3.01(s, 6H), 4.51 (s, 2H), 6.72-6.68 (t, J = 8.0 Hz, 1H), 6.82-6.80 (d, J = 8.0 Hz, 2H), 7.19-
1
3
7
4
3
.15 (m, 3H), 7.34-7.27 (m, 3H), 7.73-7.67 (m, 4H); C NMR (100 MHz, CDCl ) δ ppm: 30.0,
0.4, 111.7, 112.5, 116.4, 117.1, 122.6, 123.1, 123.6, 126.7, 127.7, 128.9, 137.2, 144.8, 150.1;
+
HRMS for C H N Calculated [M ] m/z 327.1735, Found 327.1736.
2
7
21

ACCEPTED MANUSCRIPT
2
-(3-benzylimidazo[1,2-a]pyridin-2-yl)phenol (5a): Pale yellow solid: Melting point: 134-136
0
C; IR (KBr): 3253, 3059, 3020, 3003, 2941, 2791, 2731, 2337, 1899, 1737, 1583, 1494, 1450,
-1 1
1
382, 1323, 1253, 1213, 1130, 1074, 964, 734, 721, 694, 665 cm ; H NMR (400 MHz, CDCl )
3
δ ppm: 4.57 (s, 2H), 6.84-6.78 (q, J = 8.0 Hz, 2H), 7.09-7.07 (d, J = 8.0 Hz, 1H), 7.18-7.16 (d, J
8.0 Hz, 2H), 7.33-7.21 (m, 5H), 7.52-7.50 (d, J = 8.0 Hz, 1H), 7.65-7.63 (d, J = 8.0 Hz, 1H),
=
1
3
7
1
1
.79-7.77 (d, J = 8.0 Hz, 1H), 12.61 (bs, 1H); C NMR (100 MHz, CDCl ) δ ppm: 30.2, 113.0,
3
16.7, 117.2, 117.4, 117.6, 119.1, 123.0, 124.9, 126.7, 127.1, 127.7, 129.1, 129.5, 136.1, 142.0,
+
42.9, 157.5; HRMS for C27
H
21N Calculated [M ] m/z 300.1263, Found 300.1263.
2
1
1
-(3-benzyl-8-methylimidazo[1,2-a]pyridin-2-yl)phenol (5b): Yellow solid; Melting point:
0
29-131 C; IR (KBr): 3228, 3136, 3059, 2991, 2777, 2709, 2335, 1788, 1724, 1600, 1489,
-1 1
379, 1363, 1251, 1211, 1122, 1072, 935, 732, 713, 694 cm ; H NMR (400 MHz, CDCl ) δ
3
ppm: 2.67 (s, 3H), 4.60 (s, 2H), 6.77-6.74 (t, J = 8.0 Hz, 1H), 6.87-6.84 (t, J = 8.0 Hz, 1H), 7.13-
.07 (q, J = 8.0 Hz, 2H), 7.21-7.19 (d, J = 8.0 Hz, 2H), 7.36-7.25 (m, 4H), 7.56-7.54 (d, J = 8.0
7
1
3
Hz, 1H), 7.70-7.68 (d, J = 8.0 Hz, 1H), 12.88 (bs, 1H); C NMR (100 MHz, CDCl
3
) δ ppm:
1
1
6.8, 30.4, 113.1, 117.5, 117.5, 119.0, 120.8, 123.9, 126.6, 126.7, 127.0, 127.7, 129.1, 129.4,
+
36.3, 141.3, 143.3, 157.5; HRMS for C H N Calculated [M ] m/z 314.1419, Found 314.1421.
2
7
21
2
1
1
-(3-benzyl-7-methylimidazo[1,2-a]pyridin-2-yl)phenol (5c): Yellow solid; Melting point:
0
68-170 C; IR (KBr): 3348, 3082, 3055, 3022, 2968, 2879, 2330, 1737, 1614, 1579, 1448,
-1 1
3
427, 1355, 1290, 1257, 1199, 1086, 987, 864, 748, 725, 675 cm ; H NMR (400 MHz, CDCl )
δ ppm: 2.44 (s, 3H), 4.58 (s, 2H), 6.67-6.65 (d, J = 8.0 Hz, 1H), 6.86-6.82 (t, J = 8.0 Hz, 1H),
7
7
.11-7.09 (d, J = 8.0 Hz, 1H), 7.21-7.19 (d, J = 8.0 Hz, 2H), 7.36-7.23 (m, 4H), 7.43 (s, 1H),
1
3
.53-7.51 (d, J = 8.0 Hz, 1H), 7.70-7.68 (d, J = 8.0 Hz, 1H), 12.78 (bs, 1H); C NMR (100
MHz, CDCl ) δ ppm: 21.2, 30.2, 115.2, 115.5, 116.5, 117.5, 117.6, 119.0, 122.2, 126.6, 127.0,
3

ACCEPTED MANUSCRIPT
+
1
3
27.7, 129.1, 129.3, 136.0, 136.4, 141.6, 143.3, 157.5; HRMS for C27
14.1419, Found 314.1423.
H21N Calculated [M ] m/z
2
1
1
-(3-benzyl-6-bromoimidazo[1,2-a]pyridin-2-yl)phenol (5d): White solid; Melting point: 190-
0
92 C; IR (KBr): 3331, 3084, 3034, 2979, 2817, 2337, 1722, 1577, 1492, 1450, 1413, 1381,
-1 1
328, 1251, 1199, 1116, 1074, 1028, 800, 752, 673, 663 cm ; H NMR (400 MHz, CDCl ) δ
3
ppm: 4.58 (s, 2H), 6.87-6.83 (t, J = 8.0 Hz, 1H), 7.12-7.10 (d, J = 8.0 Hz, 1H), 7.18-7.20 (d, J =
8
1
1
.0 Hz, 2H), 7.40-7.26 (m, 5H), 7.52-7.49 (dd, J = 16, 4.0 Hz, 1H), 7.59-7.57 (d, J = 8.0 Hz,
13
H), 7.95 (s, 1H), 12.35 (bs, 1H); C NMR (100 MHz, CDCl ) δ ppm: 30.2, 107.8, 116.9, 117.3,
3
17.7, 119.2, 122.9, 126.8, 127.3, 127.6, 128.3, 129.3, 129.8, 135.5, 141.3, 142.9, 157.5; HRMS
+
for C H N Calculated [M ] m/z 378.0368, Found 378.0375.
2
7
21
2
-(3-benzylimidazo[1,2-a]pyridin-2-yl)-6-methoxyphenol (5e): Pale yellow solid; Melting
0
point: 141-143 C; IR (KBr): 3342, 3102, 3005, 2983, 2688, 2335, 1788, 1737, 1598, 1454,
-1 1
1
415, 1384, 1363, 1284, 1238, 1217, 1178, 1089, 1045, 817, 732, 692 cm ; H NMR (400 MHz,
CDCl ) δ ppm: 3.97 (s, 3H), 4.59 (s, 2H), 6.84-6.78 (q, J = 8.0 Hz, 2H), 6.92-6.90 (d, J = 8.0 Hz,
3
1
H), 7.20-7.17 (m, 3H), 7.36-7.25 (m, 5H), 7.69-7.67 (d, J = 8.0 Hz, 1H), 7.81-7.79 (d, J = 8.0
1
3
Hz, 1H); C NMR (100 MHz, CDCl ) δ ppm: 30.3, 56.1, 111.7, 112.9, 116.9, 117.4, 117.7,
3
1
18.5, 118.9, 123.0, 124.9, 127.0, 127.7, 129.1, 136.2, 142.0, 142.8, 147.4, 149.1; HRMS for
+
C H N Calculated [M ] m/z 330.1368, Found 330.1370.
27
21
2
-(3-benzyl-8-methylimidazo[1,2-a]pyridin-2-yl)-6-methoxyphenol (5f): Pale yellow solid;
0
Melting point: 169-171 C; IR (KBr): 3332, 3134, 3062, 3026, 2983, 2833, 2727, 2331, 1651,
-1 1
1
585, 1492, 1440, 1381, 1251, 1232, 1170, 1112, 1047, 975, 829, 771, 715 cm ; H NMR (400
MHz, CDCl ) δ ppm: 2.43 (s, 3H), 3.97 (s, 3H), 4.57 (s, 2H), 6.65-6.63 (d, J = 8.0 Hz, 1H), 6.81-
3

ACCEPTED MANUSCRIPT
6
.77 (t, J = 8.0 Hz, 1H), 6.91-6.89 (d, J = 8.0 Hz, 1H), 7.16-7.15 (d, J = 4.0 Hz, 1H), 7.19-7.17
1
3
(
d, J = 8.0 Hz, 2H), 7.35-7.26 (m, 4H), 7.44 (bs, 1H), 7.69-7.67 (d, J = 8.0 Hz, 1H); C NMR
(
100 MHz, CDCl ) δ ppm: 21.2, 30.2, 56.1, 111.6, 115.3, 115.5, 116.7, 117.9, 118.4, 118.8,
3
1
22.2, 127.0, 127.7, 129.0, 136.0, 136.4, 141.6, 143.2, 147.5, 149.1; HRMS for C H N
27 21
+
Calculated [M ] m/z 344.1525, Found 344.1526.
2
-(3-benzyl-7-methylimidazo[1,2-a]pyridin-2-yl)-6-methoxyphenol (5g): Yellow solid;
0
Melting point: 164-166 C; IR (KBr): 3334, 3062, 3026, 2983, 2833, 2727, 2331, 1788, 1737,
-1 1
1
602, 1583, 1494, 1440, 1381, 1251, 1170, 1089, 1029, 929, 815, 771, 728, 715 cm ; H NMR
(
400 MHz, CDCl ) δ ppm: 2.44 (s, 3H), 3.97 (s, 3H), 4.57 (s, 2H), 6.66-6.64 (d, J = 8.0 Hz, 1H),
3
6
7
.81-6.77 (t, J = 8.0 Hz, 1H), 6.91-6.89 (d, J = 8.0 Hz, 1H), 7.16-7.15 (d, J = 4.0 Hz, 1H), 7.20-
1
3
.18 (d, J = 8.0 Hz, 2H), 7.36-7.26 (m, 4H), 7.45 (bs, 1H), 7.69-7.67 (d, J = 8.0 Hz, 1H); C
NMR (100 MHz, CDCl ) δ ppm: 21.2, 30.3, 56.1, 111.5, 115.4, 115.5, 116.7, 117.9, 118.4,
3
1
21
18.8, 122.2, 127.0, 127.7, 129.1, 136.0, 136.4, 141.6, 143.2, 147.4, 149.1; HRMS for C27H N
+
Calculated [M ] m/z 344.1525, Found 344.1529.
2
-(3-benzyl-6-bromoimidazo[1,2-a]pyridin-2-yl)-4-bromophenol (5h): Yellow solid; Melting
0
point: 220-222 C; IR (KBr): 3439, 3217, 3130, 3086, 3011, 2987, 2876, 2337, 1757, 1573,
-1 1
1
450, 1436, 1282, 1243, 1197, 1070, 986, 796, 721, 692 cm ; H NMR (400 MHz, CDCl ) δ
3
ppm: 4.56 (s, 2H), 6.99-6.97 (d, J = 8.0 Hz, 1H), 7.19-7.17 (d, J = 8.0 Hz, 2H), 7.40-7.28 (m,
1
3
6
H), 7.59-7.57 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 8.01 (s, 1H), 12.46 (bs, 1H); C NMR (100
MHz, CDCl
3
) δ ppm: 30.1, 110.8, 117.4, 118.4, 118.7, 119.5, 123.0, 127.5, 127.6, 128.7, 129.1,
+
1
4
29.4, 132.4, 135.2, 141.2, 156.6; HRMS for C27
55.9478.
H
21N Calculated [M ] m/z 455.9473, Found

ACCEPTED MANUSCRIPT
2
1
1
-(3-benzylimidazo[1,2-a]pyridin-2-yl)-4-bromophenol (5i): Yellow solid; Melting point:
0
33-135 C; IR (KBr): 3379, 3116, 3062, 3026, 2831, 2331, 1743, 1579, 1483, 1436, 1367,
-1 1
350, 1286, 1253, 1230, 1170, 1080, 756, 725, 700, 686, 615 cm ; H NMR (400 MHz, CDCl )
3
δ ppm: 4.59 (s, 2H), 6.89-6.85 (t, J = 8.0 Hz, 1H), 7.00-6.98 (d, J = 8.0 Hz, 1H), 7.19-7.17 (d, J
8.0 Hz, 2H), 7.37-7.29 (m, 5H), 7.64-7.63 (d, J = 4.0 Hz, 1H), 7.68-7.66 (d, J = 8.0 Hz, 1H),
=
1
3
7
1
1
.88-7.86 (d, J = 8.0 Hz, 1H), 12.72 (bs, 1H); C NMR (100 MHz, CDCl ) δ ppm: 30.2, 110.7,
3
13.2, 116.9, 117.9, 119.2, 119.4, 123.1, 125.3, 127.2, 127.6, 129.0, 129.2, 132.0, 135.8, 140.4,
+
42.8, 156.7; HRMS for C27
H
21N Calculated [M ] m/z 378.0368, Found 378.0369.
2
-(3-benzyl-8-methylimidazo[1,2-a]pyridin-2-yl)-4-bromophenol (5j): Yellow solid; Melting
0
point: 155-157 C; IR (KBr): 3427, 3100, 3064, 3020, 2996, 2876, 2337, 1767, 1567, 1472,
-1 1
1
361, 1209, 1029, 840, 815, 738, 721, 692, 667 cm ; H NMR (400 MHz, CDCl ) δ ppm: 2.66
3
(s, 3H), 4.58 (s, 2H), 6.80-6.77 (t, J = 8.0 Hz, 1H), 6.99-6.97 (d, J = 8.0 Hz, 1H), 7.11-7.09 (d, J
=
8.0 Hz, 1H), 7.19-7.17 (d, J = 8.0 Hz, 2H), 7.36-7.27 (m, 4H), 7.64 (s, 1H), 7.75-7.73 (d, J =
1
3
8
1
3
.0 Hz, 1H), 13.05 (bs, 1H); C NMR (100 MHz, CDCl ) δ ppm: 16.7, 30.3, 110.7, 113.3,
18.3, 119.3, 120.8, 124.2, 126.8, 127.2, 127.7, 128.9, 129.2, 131.9, 136.0, 139.7, 143.2, 156.7;
+
HRMS for C H N Calculated [M ] m/z 392.0524, Found 392.0527.
2
7
21
2
-(3-benzyl-7-methylimidazo[1,2-a]pyridin-2-yl)-4-bromophenol (5k): Yellow solid; Melting
0
point: 221-223 C; IR (KBr): 3369, 3932, 2983, 2735, 2612, 2337, 1737, 1726, 1573, 1477,
-
1 1
1
435, 1415, 1357, 1278, 1253, 1230, 1217, 1155, 945, 808, 725, 680 cm ; H NMR (400 MHz,
CDCl ) δ ppm: 2.44 (s, 3H), 4.54 (s, 2H), 6.69-6.67 (d, J = 8.0 Hz, 1H), 6.98-6.96 (d, J = 8.0 Hz,
H), 7.18-7.16 (d, J = 8.0 Hz, 2H), 7.41-7.30 (m, 5H), 7.61 (s, 1H), 7.74-7.72 (d, J = 8.0 Hz,
3
1
1
1
3
H), 12.92 (bs, 1H); C NMR (100 MHz, CDCl ) δ ppm: 21.3, 30.1, 110.6, 115.3, 115.8, 117.3,
3

ACCEPTED MANUSCRIPT
1
19.3, 119.4, 122.3, 127.2, 127.6, 128.9, 129.2, 131.8, 136.0, 136.5, 140.0, 143.2, 156.7; HRMS
+
for C H N Calculated [M ] m/z 392.0524, Found 392.0522.
2
7
21
Supplementary data
1
13
H and C NMR spectra for all the compounds and optical data were included. CIF data of
compound 5d also included. This material is available free of charge via the Internet at
Acknowledgements
Balijapalli Umamahesh thanks CSIR for providing Senior Research Fellowship. The DST-FIST
NMR facility at VIT University and VIT management are duly acknowledged.
References
[1] Fisher M H, Lusi A. Imidazo[1,2-a]pyridine anthelmintic and antifungal agents. Journal of
Medicinal Chemistry 1972;15:982-85.
[2] Kang C W, Sun Y, Valle J R D. Substituted imidazo[1,2-a]pyridines as β-Strand
peptidomimetics. Organic letters 2012;14:6162-65.
[3] Roy M, Chakravarthi B V S K, Jayabaskaran C, Karande A A, Chakravarty A R. Impact
of metal binding on the antitumor activity and cellular imaging of a metal chelator
cationic imidazopyridine derivative. Dalton Transctions 2011;40:4855.
[4] Moraski G C, Oliver A G, Markley L D, Cho S, Franzblau S G, Miller M J. Scaffold
switching: An exploration of 5,6-fused bicyclic heteroaromatics systems to afford
antituberculosis activity akin to the imidazo[1,2-a]pyridine-3-carboxylates Bioorganic &
Medicinal Chemistry Letters 2014;24:3493-98.
[5] Yngve U, Söderman P, Svensson M, Rosqvist S, Arvidsson P I. Imidazopyridine-based
inhibitors of glycogen synthase kinase 3: synthesis and evaluation of amide isostere replacements
of the carboxamide Scaffold. Chemistry & Biodiversity 2012;9:2442–2452.

ACCEPTED MANUSCRIPT
[6] Nair D K, Mobin S M, Namboothiri I N N. Synthesis of imidazopyridines from the Morita–
Baylis–Hillman acetates of nitroalkenes and convenient access to alpidem and zolpidem. Organic
Letters 2012;14:4580-83.
[7] Guetzoyan L, Nikbin N, Baxendale I R, Ley S V. Flow chemistry synthesis of zolpidem,
alpidem and other GABA agonists and their biological evaluation through the use of in-line
A
frontal affinity chromatography. Chemical Science 2013;4:764-69.
[8] Benavides J, Peny B, Scatton B. The imidazopyridine derivatives zolpidem and alpidem
discriminate between central ω (benzodiazepine) receptor subtypes in rat brain sections.
European Neuropsychopharmacology. 1991;1:398.
[9] Mutai T, Tomoda H, Ohkawa T, Yabe Y, Araki K. Switching of polymorph dependent
ESIPT luminescence of an imidazo[1,2-a]pyridine derivative. Angewandte Chemie International
Edition. 2008;47:9522-24.
[10] Shono H, Ohkawa T, Tomoda H, Mutai T, Araki K. Fabrication of colorless organic
materials exhibiting white luminescence using normal and excited state intramolecular proton
transfer processes. ACS Applied Materials and Interfaces 2011;3:654-57.
[
11] Seferoglu Z, Ihmels H, Sahin E. Synthesis and photophysical properties of fluorescent aryls
tyrylimidazo[1,2-a]pyridine based donor-acceptor chromophores. Dyes and Pigments.
015;113:465-73.
2
[
12] Douhal A, Amat-Guerri F, Acuna A U. Photoinduced intramolecular proton transfer and
charge redistribution in imidazopyridines. Journal of Physical Chemistry 1995;99:76-80.
13] Prostota Y, Kachkovsky, O D, Reis, L V, Santo, P F. New unsymmetrical squaraine dyes
derived from imidazo[1,5-a]pyridine. Dyes and Pigments 2013;96:554-62.
[
[14] Firmansyah D, Ciuciu A I, Hugues V, Blanchard-Desce M, Flamigni L, Gryko D T. Bright,
fluorescent dyes based on imidazo[1,2-a]pyridines that are capable of two-photon absorption.
Chemistry An Asian Journal 2013; 8:1279-94.
[15] Ge, Y Q, Jia J, Yang H, Tao X T, Wang J W. The synthesis, characterization and optical
properties of novel pyrido[1,2-a]benzimidazole derivatives. Dyes and Pigments 2011;88:344-49.

ACCEPTED MANUSCRIPT
[16] Nagarajan N, Velmurugan G, Prakash A, Shakti N, Katiyar M, Venuvanalingam P,
Renganathan R. Highly emissive luminogens based on imidazo[1,2-a]pyridine for
electroluminescent applications. Chemistry An Asian Journal 2014;9:294-04.
[17] Chen, K –Y, Hsieh C –C, Cheng Y –M, Lai C –H, Chou P -T. Extensive spectral tuning of
the proton transfer emission from 550 to 675 nm via a rational derivatization of 10-
hydroxybenzo[h]quinoline.Chemical Communications 2006;4395–97.
[18] Furukawa S, Shono H, Mutai T, Araki K. Colorless, transparent, dye-doped polymer films
exhibiting tunable luminescence color: Controlling the dual-color luminescence of 2-(2′-
hydroxyphenyl)imidazo[1,2-a]pyridine derivatives with the surrounding matrix. ACS Applied
Materials and Interfaces 2014;6:16065-70.
[19]. Liu P, Deng C –L, Lei X, Lin G -Q. Tandem amination/cycloisomerization of aryl
propargylic alcohols with 2-aminopyridines as an expedient route to imidazo[1,2-a]pyridines.
European Journal of Organic Chemistry 2011;7308-16.
[20] Kaswan P, Pericherla K, Rajnikant, Kumar A. Synthesis of 3-aroylimidazo[1,2-a]pyridines
via CuCl catalyzed tandem dual carbon enitrogen bonding. Tetrahedron 2014;20:8539-8544.
2
[21] Zhang Y, Chen Z, Wu W, Zhang Y, Su W. CuI-catalyzed aerobic oxidative α-aminaton
cyclization of ketones to access aryl or alkenyl substituted imidazoheterocycles. Journal of
Organic Chemistry 2013;78:12494-04.
[22] Wang, Y.; Frett, B.; Li, H. Efficient access to 2,3-diarylimidazo[1,2-a]pyridines via a one-
pot, ligand-free, palladium-catalyzed three-component reaction under microwave irradiation.
Organic Letters 2014;16:3016-19.
[23] Yu J, Jin Y, Zhang H, Yang X, Fu H. Copper-catalyzed aerobic oxidative C-H
functionalization of substituted pyridines: synthesis of imidazopyridine derivatives. Chemistry A
European Journal 2013;19:16804-08.
[24] Maleki A, Javanshir S, Naimabadi M. Facile synthesis of imidazo[1,2-a]pyridines via a one-
pot three-component reaction under solvent-free mechanochemical ball-milling conditions. RSC
Advances 2014;4:30229-32.

ACCEPTED MANUSCRIPT
[25] Kielesiński Ł, Tasior M, Gryko D T. Polycyclic imidazo[1,2-a]pyridine analogs –
synthesis via oxidative intramolecular C–H amination and optical properties. Organic Chemistry
Frontiers 2015;2:21-28.
[
26] Reddy B V S, Reddy P S, Reddy Y J, Yadav J S. InBr
one-pot synthesis of imidazo[1,2-a]pyridines. Tetrahedron Letters 2011;52:5789-93.
27] Liu P, Fang L, Lei X, Lin G. Synthesis of imidazo[1,2a]pyridines via three-component
reaction of 2-aminopyridines, aldehydes and alkynes. Tetrahedron Letters 2010, 51, 4605-
8.
28] Chernyak N, Gevorgyan V. General and efficient copper-catalyzed three-component
3
-catalyzed three-component,
[
0
[
coupling reaction towards imidazoheterocycles: one-pot synthesis of alpidem and zolpidem.
Angewandte chemie international edition 2010;49:2743-46.
4
[29] Guchhait S K, Chandgude A L, Priyadarshani G. CuSO –Glucose for in situ generation of
controlled Cu (I)–Cu (II) bicatalysts: Multicomponent reaction of heterocyclic azine and
aldehyde with alkyne, and cycloisomerization toward synthesis of N-fused imidazoles. Journal of
Organic Chemistry 2012;77:4438-44.
[30]. Umamahesh B, Mandlimath T R, Sathiyanarayanan K I. A novel, facile, rapid, solvent free
protocol for the one pot green synthesis of chromeno[2,3-d]pyrimidines using reusable nano
ZnAl O –a NOSE approach and photophysical studies. RSC Advances 2015;5:6578-87.
2
4
[31] Stasyuk A J, Banasiewicz M, Cyranski M K, Gryko D T. Imidazo[1,2-a]pyridines
susceptible to excited state intramolecular proton transfer: One-pot synthesis via an Ortoleva–
King reaction. Journal of Organic Chemistry 2012;77:5552-58.
[32] Bagdi A K, Rahman M, Santra S, Majee A, Hajra A. Copper-catalyzed synthesis of
imidazo[1,2-a]pyridines through tandem imine formation-oxidative cyclization under ambient
air: One-step synthesis of zolimidine on a gram-scale. Advanced Synthesis and Cataysis
2
013;355:1741-47.
[33]. Li W, Lin W, Wang J, Guan X. Phenanthro[9,10-d]imidazole-quinoline boron difluoride
dyes with solid-state red fluorescence. Organic Letters 2013;15:1768-71.

ACCEPTED MANUSCRIPT
[34] Easwaramoorthi S, Umamahesh B, Cheranmadevi P, Rathore R S, Sathiyanarayanan K I.
Synthesis of green light emitting fused pyrazolinopiperidines-photophysical and electrochemical
studies. RSC adv. 2013;3:1243-54.
[35] Mutai T, Sawatani H, Shida T, Shono H Araki K. Tuning of excited-state intramolecular
proton transfer (ESIPT) fluorescence of imidazo[1,2-a]pyridine in rigid matrices by substitution
effect. Journal of Organic Chemistry 2013;78:2482-89.
[36] Tang K C, Chang M J, Lin T Y, Pan H A, Fang T C, Chen K Y, Hung W Y, Hsu Y H, Chou
P T. Fine tuning the energetics of excited-state intramolecular proton transfer (ESIPT): white
light generation in a single ESIPT system. Journal of American Chemical Society
2
011;133:17738-45.
[37] Sakai K, Ishikawaa T, Akutagawa T. A blue-white-yellow color-tunable excited state
intramolecular proton transfer (ESIPT) fluorophore: sensitivity to polar–nonpolar solvent ratios.
Journal of Material Chemistry C 2013;1:7866-71.
[38] Seo J, Kim S, Park S Y. Strong solvatochromic fluorescence from the intramolecular
charge-transfer state created by excited-state intramolecular proton transfer. Journal of American
Chemical Society 2004;126:11154-55.
[
39] Stasyuk A J, Banasiewicz M, Ventura B, Cyranski M K, Gryko D T. Benzo[a]imidazo
5,1,2-cd]indolizines – a new class of molecules displaying excited state intramolecular proton
[
transfer. New Journal of Chemistry 2014;38:189-97.
40] Basaric N, Doslic N, Ivkovic J, Wang Y H Veljkovic J, Mlinaric-Majerski K, Wan P.
[
Excited state intramolecular proton transfer (ESIPT) from phenol to carbon in selected
phenylnaphthols and naphthylphenols. Journal of Organic Chemistry 2013;78:1811-23.
[41] Piechowska J, Gryko D T. Preparation of a family of 10-Hydroxybenzo[h]quinoline
analogues via a modified Sanford reaction and their excited state intramolecular proton transfer
properties. Journal of Organic Chemistry 2011;76:10220-28.

ACCEPTED MANUSCRIPT
[
42] Shigemitsu Y, Mutai T, Houjou H, Araki K. Excited-state intramolecular proton transfer
ESIPT) emission of hydroxyphenylimidazopyridine: computational study on enhanced and
(
polymorph-dependent luminescence in the solid state. Journal of Physical Chemistry A
012;116:12041-48.
43] Douhal A, Amat-Guerri F, Acuña A U. Photoinduced intramolecular proton transfer and
charge redistribution in imidazopyridines. Journal of Physical Chemistry 1995;99:76–80.
2
[
[44] Douhal A, The involvement of rotational processes in the intramolecular proton-transfer
cycle. Berichte der bunsengesellschaft für physikalische Chemie 1998;102:448-51.

ACCEPTED MANUSCRIPT
Tables
Table 1. Screening of optimized reaction conditions for the synthesis of imidazo[1,2-a]pyridine.
2
Table 2. Optical properties of imidazo[1,2-a]pyridine derivatives.
4
5
Table 3. Fluorescence properties of selected derivatives in various solvents.
1

ACCEPTED MANUSCRIPT
Table 1. Screening of optimized reaction conditions for the synthesis of imidazo[1,2-a]pyridine.
Entry
Catalyst (mol %)
CuCl (10)
Co-catalyst (mol %) Solvent
Time (h)
24
% Yield (rt)
15
1
2
3
4
5
6
7
8
9
-
-
-
-
-
-
-
-
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
CuBr (10)
24
18
CuI (10)
24
35
CuSO
4
(10)
24
39
Cu(OAc) (10)
24
36
2
CuO (10)
24
38
Cu O (10)
24
38
2
CuAl
2
O
4
(10)
24
46
CuO/CuAl O (10) -
24
50
2
4
1
1
1
1
1
1
1
0
1
2
3
4
5
6
CuO/CuAl O (10) TsOH
24
55
2
4
CuO/CuAl O (10) TEA
24
53
2
4
CuO/CuAl
2
O
4
(10) D-Glucose (20)
24
67(10)
77(10)
78(10)
80(13)
88(15)
CuO/CuAl O (15) D-Glucose (20)
18
2
4
CuO/CuAl O (20) D-Glucose (20)
18
2
4
CuO/CuAl O (15) D-Glucose (25)
18
2
4
CuO/CuAl
2
O
4
(15) D-Glucose (30)
18
2

ACCEPTED MANUSCRIPT
1
1
1
2
2
2
2
2
2
7
8
9
0
1
2
3
4
5
CuO/CuAl
2
O
4
(15) D-Glucose (30)
EtOH
24
24
24
24
24
24
24
24
24
63
40
44
32
29
21
-
CuO/CuAl O (15) D-Glucose (30)
CH CN
2
4
3
CuO/CuAl O (15) D-Glucose (30)
THF
2
2
2
4
4
4
CuO/CuAl
CuO/CuAl
O
O
(15) D-Glucose (30)
(15) D-Glucose (30)
DMF
EtOAc
Dioxane
DMSO
neat
CuO/CuAl O (15) D-Glucose (30)
2
4
CuO/CuAl O (15) D-Glucose (30)
2
2
2
4
4
4
CuO/CuAl
CuO/CuAl
O
O
(15) D-Glucose (30)
(15) D-Glucose (30)
-
Water
-
Reaction conditions: A mixture of benzaldehydes (10 mmol), 2-aminopyridine (1) (10 mmol),
phenylacetylene (2) (13 mmol) and catalyst were taken 10 mL dry solvent and the reaction
mixture was refluxed for 24h.
3