Copper catalyzed direct aerobic double-oxidative cross-dehydrogenative coupling of imidazoheterocycles with aryl acetaldehydes: An articulate approach for dicarbonylation at C-3 position

Article abstract of DOI:10.1016/j.tet.2015.12.012

Direct aerobic oxidative cross-dehydrogenative coupling of aryl acetaldehydes at C-3 position of imidazoheterocycles via copper catalyzed reaction resulted in the synthesis of dicarbonylated imidazoheterocycles in 55-85% yields. The methodology provides a

Full text of DOI:10.1016/j.tet.2015.12.012

Accepted Manuscript
Copper catalyzed direct aerobic double-oxidative cross-dehydrogenative coupling
of imidazoheterocycles with aryl acetaldehydes: An articulate approach for
dicarbonylation at C-3 position
S.M.Abdul Shakoor, Devesh S. Agarwal, Anil Kumar, Rajeev Sakhuja
PII:
S0040-4020(15)30262-3
10.1016/j.tet.2015.12.012
TET 27338
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 3 September 2015
Revised Date: 3 November 2015
Accepted Date: 2 December 2015
Please cite this article as: Shakoor SMA, Agarwal DS, Kumar A, Sakhuja R, Copper catalyzed
direct aerobic double-oxidative cross-dehydrogenative coupling of imidazoheterocycles with aryl
acetaldehydes: An articulate approach for dicarbonylation at C-3 position, Tetrahedron (2016), doi:
10.1016/j.tet.2015.12.012.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Copper catalyzed direct aerobic double-
oxidative cross-dehydrogenative coupling of
imidazoheterocycles with aryl acetaldehydes:
An articulate approach for dicarbonylation
at C-3 position
Leave this area blank for abstract info.
S. M. Abdul Shakoor, Devesh S. Agarwal, Anil Kumar, Rajeev Sakhuja
Department of Chemistry
Birla Institute of Technology & Science, Pilani
Rajasthan, 333031, India

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Copper catalyzed direct aerobic double-oxidative cross-dehydrogenative
coupling of imidazoheterocycles with aryl acetaldehydes: An articulate approach
for dicarbonylation at C-3 position
S. M. Abdul Shakoora, Devesh S. Agarwala, Anil Kumara, Rajeev Sakhujaa,*
aDepartment of Chemistry, Birla Institute of Technology & Science, Pilani, Rajasthan, 333031, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Direct aerobic oxidative cross-dehydrogenative coupling of aryl acetaldehydes at C-3 position of
imidazoheterocycles via copper catalyzed reaction resulted in the synthesis of dicarbonylated
imidazoheterocycles in 55-85% yields. The methodology provides a straightforward, high
yielding and one-pot approach towards the synthesis of C-3 dicarbonylated imidazoheterocycles
without prior activation of C(sp2)-H or a base. This also reports the first method of coupling of
aryl acetaldehydes on imidazo[1,2-a]pyridine system via double-oxidative cross-dehydogenative
process.
Available online
Keywords:
Aryl acetaldehyde
Imidazo[1,2-a]pyridine
Oxidative
2009 Elsevier Ltd. All rights reserved
.
Cross-dehydrogenative coupling
Aerobic
nitrosylation employing tert-butyl nitrite (t-BuNO),19,20] (vii)
thiocyanation using eosin Y as a photoredox catalyst in visible
light,21 (viii) sulfenylation using thiols,22a-b disulfides,23a-d sodium
sulfinates,24 and sulfonyl hydrazides,25 (ix) formylation by
DMSO26 or by conventional vilsmeier-Haack method27 and (x)
glyoxalation with ethyl oxalyl chloride.28a-b
1. Introduction
Imidazo[1,2-a]pyridine is a premium structural framework
that has received remarkable attention in recent years because of
its presence in numerous biologically important scaffolds1 and
currently marketed drugs such as alpidem, necopidem, zolpidem,
optically active GSK812397, and zolimidine.2a-e The anticancer,
antiviral, antipyretic, analgesic, and anti-HIV activities of
imidazo[1,2-a]pyridines derivative are also well documented.3
This core structure is also cited in various bioactive compounds,
such as liver X receptor (LXR) agonists,4 GABAAα2/α3
agonists,5 γ-secretase modulators (GSMs)6 and positive allosteric
modulators (PAMs) of metabotropic glutamate 2 receptor.7 In
addition to this, compounds with this framework exhibit versatile
applications in material sciences8 and agrochemicals.9
The increasing citation of this privileged scaffold in recent
articles allude the interest of organic chemist towards the
construction of more bioactive functionalized imidazo[1,2-
a]pyridines. More specifically, the transition-metal catalyzed
functionalization of imidazo[1,2-a]pyridines in recent years10 has
opened new doors for the synthesis of novel heterocyclic
systems. Some examples of direct C-3 functionalization of
imidazo[1,2-a]pyridines includes (Figure 1) (i) arylation with
aryl halides,11 or oxidative cross-coupling with arenes,12 (ii)
oxidative α- or β-alkenylation with alkenes,13-14 vinyl halides15
and acrylates,16 (iii) amidoalkylation via multi-component
reaction,17 (iv) hydrazination with diethyl azodicarboxylate,18 (v)
trifluoromethylation using Langlois (NaSO2CF3) reagent, (vi)
Fig. 1. Few examples of C-3 functionalization of
imidazo[1,2-a]pyridine
Despite these significant progresses for C-3 functionalization
of imidazo[1,2-a]pyridines, there is no report on the direct cross-
dehydrogenative coupling (CDC) between aldehydic C(sp2)-H

2
Tetrahedron
and C3(sp2)–H of imidazo[1,2-a]pyridines. During the progress
Table 1. Optimization of the Reaction Conditionsa for
ACCEPTED MANUSCRIPT
of this work, Atmakur et al. reported I2-DMSO-PTSA catalyzed
C-3 dicarbonylation of imidazo[1,2-a]pyridines using
acetophenones.29 However, developing alternate strategies for
dicarbonyl insertion at C-3 position of imidazo[1,2-a]pyridines
remains a challenging task.
Synthesis of 3a
Entr
y
Catalysts
Solvent
Oxidant
Ligand
Yield
(%)
.
Cu(OAc)2
CuI
Toulene
Toulene
Toulene
Toulene
Toluene
Toulene
DCE
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
K2S2O8
CAN
-
-
-
-
-
-
-
-
-
-
-
-
-
-
46
42
45
38
60
20
55
30
56
63
64
42
46
66
72
2.
Verily
transition-metal
catalyzed
aerobic
cross-
3.
CuCl
dehydrogenative coupling has become a burgeoning area in
regard with sustainable chemistry for the construction of C-C
and C-X bonds.30a-e Aldehydes have also been used for palladium
catalyzed ortho-aroylation of aromatic and heteroaromatic
systems via C(sp2)-C(sp2) cross-dehydrogenative coupling.31-34
Ning Jiao and co-workers successively described CuBr catalyzed
oxidative cross-dehydrogenative C(sp2)-N bond formation
strategies for the synthesis of α-ketoamides with aryl
acetaldehyde and phenyl glyoxal respectively.35,36 In continuation
of our28b effort on the regioselective funtionalization of
imidazo[1,2-a]pyridines, we herein disclose an efficient
methodology for copper catalyzed C-3 dicarbonylation of
4.
CuO
5.
CuBr
6.
CuSO4.5H2O
CuBr
7.
8.
CuBr
DCM
9.
CuBr
Xylene
Toulene
Toulene
Toulene
Toulene
Toulene
Toulene
10.
11.
12.
13.
14.
15.
CuBr
CuBr
imidazo[1,2-a]pyridines;
whereby
oxidative
cross-
CuBr
m-CPBA
BPO
dehydrogenative coupling and oxidation of methylene next to
phenyl group of aryl acetaldehydes proceeds in a cumulative
manner.
CuBr
CuBr
Air
CuBr
Air
1,10-
2. Results and Discussion
phenanthroli
ne
Our preliminary investigation started with the reaction of
imidazo[1,2-a]pyridine (1a) and phenyl acetaldehyde (2a) in the
presence of catalytic amount of copper acetate (10 mol%) and
TBHP (1 eq.) as oxidant in toluene at 100 °C. To our delight
expected product, 1-phenyl-2-(2-phenylimidazo[1,2-a]pyridin-3-
yl)ethane-1,2-dione (3a) was obtained in 46% yield after 20 h.
The structure of the 3a was confirmed by its detailed
16.
17.
CuBr
CuBr
Toulene
Toulene
Air
Air
TMDEA
67
80
2,2-
bipyridine
18.
19.
20.
21.
22.
23.
24.
CuBr
Touleneb
Toulene
Toulene
Toulene
Toulene
Toulene
Toulene
Air
2,2-
bipyridine
80
1
InCl3
Air
2,2-
bipyridine
52
spectroscopic analysis. The H NMR of compound 3a exhibited
14 protons in the aromatic region between δ 7.03-9.78, with the
C5-H at δ 9.78, accounting for the coupling between imidazo[1,2-
a]pyridyl nucleus and phenyl acetaldehyde. Absence of a peak
for methylene protons in the 1H NMR spectrum and the
corresponding methylene carbon in the 13C NMR spectrum
indicated that during coupling functional transformation of
methylene group has taken place. This got support from the
presence of two carbonyl peaks in the 13C NMR of 3a at δ 190.4
and 183.7. Final confirmation came from the HRMS of the 3a
that showed molecular ion peak at m/z 327.1133 [M+H]+
corresponding to the dicarbonylated product.
RuCl3
Air
2,2-
bipyridine
58
FeCl3.6H2O
Pd(OAc)2
PdCl2
Air
2,2-
bipyridine
70
TBHP
TBHP
TBHP
2,2-
bipyridine
NDc
NDc
NDc
2,2-
bipyridine
Pd(PPh3)Cl2
2,2-
bipyridine
To improve the yield of 3a several experiments were
performed and results for these experiments are summarized in
table 1. Screening of different copper catalysts revealed that best
yield (60%) was obtained by using CuBr whereas other copper
catalyst such as CuI, CuCl, and CuO gave similar yields as that of
Cu(OAc)2 (Table 1, entry 2-4). Lower yield of 3a were obtained
by using CuSO4.5H2O (Table 1, entry 6). We next undertook the
process of solvent screening. It was noticed that 3a was isolated
in comparatively lesser yield in DCM, DCE and xylene (Table 1,
entry 7-9). We next studied the effect of varying oxidant on the
coupling between 1a and 2a in toluene. An improvement in the
yield of 3a was noticed using oxidants such as K2S2O8, CAN
(Table 1, entry 10-11), while comparatively lesser yields were
observed with m-CPBA and BPO (benzoyl peroxide) (Table 1,
entry 12-13). Delightfully, the substitution of external oxidants
with air resulted in almost similar yield (Table 1, entry 14).
aReaction conditions: imidazo[1,2-a]pyridine (0.25 mmol),
phenyl acetaldehyde (0.30 mmol), catalyst (10 mol%), oxidant
(0.25 mmol), ligand (10 mol%), solvent (4 mL). The reactions
were performed and monitored at 100 °C [except for entry 7 (80
b
°C) and entry 8 (40 °C)] for 20 h; After 12 h; cND: not detected
on TLC; TMDEA: tetramethylethylenediamine; BPO: benzoyl
peroxide; TBHP: tert-butyl hydroperoxide.
To further increase the yields, we next attempted the coupling
reaction in air using a couple of ligands including 1,10-
pehenthroline, TMDEA and 2,2-bipyridine (Table 1, entry 15-
17). Among these ligands, use of 2,2-bipyridine along with CuBr
produced 80% of 3a in toluene, even when the time of the
reaction was reduced from 20 h to 12 h (Table 1, entry 17 & 18).
Encouraged by these result, we also tested other transition metal
catalysts, however employing palladium catalyst e.g: Pd(OAc)2,
PdCl2 and Pd(PPh3)Cl2 did not yield 3a in noticeable amounts
(Table 1, entry 22-24). While, InCl3, RuCl3 and FeCl3 were able
to catalyze the reaction in comparatively lesser yields (Table 1,
entry 19-21). After a great deal of screening different parameters,

3
N
the highest yield (80%) of C-3 dicarbonylated product 3a was
O
R
ACCEPTED MANUSCRIPT
R1
N
R2
CuBr (10 mol%)
obtained when 1.2 equiv. of phenyl acetaldehyde was coupled
with 1 equiv. Imidazo[1,2,a]pyridine using CuBr/2,2’-bipyridine
(10 mol% each) in toluene at 100 °C under an atmosphere of air.
H
N
2,2'- bipyridine (10 mol%)
O
R
R1
O
N
Toulene
100°C, 12-14 h
R2
Air
1
2
3
Under the optimal conditions the scope of substituted phenyl
acetaldehydes was investigated (Scheme 1). Both the electron
rich and electron deficient aldehydes (2a-g) efficiently reacted
with 2-phenylimidazo[1,2-a]pyridine (1a) to give corresponding
C-3 dicarbonylated products (3a-g) in 70-85% isolated yield.
Among aryl acetaldehydes, 4-fluorophenyl acetaldehyde showed
best yield (85%) as compared to other halo derivatives (4-Br, 4-
Cl) when reacted with 1a. Naphthyl-substituted acetaldehyde also
successfully afforded 3g in 76% isolated yield. Relatively lesser
yields of C-3 dicarbonylated products (3b & 3c) were obtained
when 4-methyl and 4-methoxy substituted phenyl acetaldehydes
were employed. Interestingly, acetaldehyde or propionaldehyde
failed to react with 1a to give the corresponding dicarbonylated
products.
N
N
N
OMe
N
F
N
N
O
O
O
O
O
O
3h
3j
3i
Cl
Cl
80%
75%
78%
N
N
N
OMe
N
N
N
NO2
O
Me
O
O
O
O
O
O
3k
3m
3l
70%
55%
N
72%
N
N
Cl
N
N
N
O
Br
O
O
O
O
3o
3p
75%
3n
Br
82%
F
77%
N
N
N
N
Cl
N
N
Br
O
O
O
O
O
O
3s
3r
74%
3q
F
78%
72%
N
N
N
N
OMe
O
O
O
O
3u
3t
73%
71%
Scheme 2. Scope of imidazo[1,2-a]pyridines
& aryl
acetaldehydes
To extend the scope of our methodology, few other
imidazoheterocyles such as imidazo[1,2-a]pyrimidine (4a),
imidazo[2,1-b]thiazole (4b) and benzo[d]imidazo[2,1-b]thiazole
(4c) were reacted with phenyl acetaldehyde (2a) under similar
experimental conditions to give corresponding dicarbonylated
products (5a-c) in 68-74% isolated yields (Scheme 3).
Scheme 1. Scope of acetaldehydes
The scope of reaction was further expanded to a variety of
substituted imidazo[1,2-a]pyridines with substituted aryl
acetaldehydes (Scheme 2). Presence of both electron donating
and electron withdrawing substituents on the phenyl and pyridyl
ring in 2-phenylimidazo[1,2-a]pyridines showed a marked
difference in their reactivity towards aerial oxidative cross-
dehydrogenative coupling with aryl acetaldehydes. For example,
presence of nitro group at phenyl of 2-phenylimidazo[1,2-
a]pyridine decreased the yield of the corresponding product to
55%. However, these result demonstrated the generality of the
reaction in regard with imidazo[1,2-a]pyridine derivatives.
Scheme 3. Scope of imidazoheterocycles

4
Tetrahedron
ACCEPTED MANUSCRIPT
It is noteworthy that these imidazoheterocycles took longer
could get support from the control experiments that the reaction
reaction time to yield C-3 dicarbonylated products as compared
to imidazo[1,2-a]pyridines.
did not proceeded at all in nitrogen atmosphere or in absence of
CuBr or in presence of radical scavenger TEMPO, thereby
suggesting the crucial role of CuBr and O2 in triggering the
reaction and the possibility of radical mechanism. Further, C
was oxidized to D and subsequently to E, which then was
To gain some insights into mechanism of the reaction process,
the some control experiments were performed (Scheme 4). The
reaction did not yield the expected product at all in the presence
of radical scavenger TEMPO (3 equiv.), suggesting an evidence
for the radical mechanism. When the reaction was performed
under nitrogen atmosphere, the product was observed in traces on
TLC, thereby indicating a crucial participation of aerial oxygen
not only as an oxidant but also as an initiator to trigger the
catalytic process. The reaction of phenyl acetaldehyde under
copper bromide catalyzed refluxing condition in air did not yield
phenyl glyoxal at all thereby, suggesting that the oxidation of
phenyl acetaldehyde to phenyl glyoxal may not be involved in
the reaction. The reaction did not proceed in the absence of
copper bromide emphasizing the role of copper as an oxidant.
Interestingly, benzaldehyde (6) failed to give the corresponding
oxidized product (6a). The TLC of the reaction mixture shows
un-reacted imidazo[1,2-a]pyridine even after refluxing for 12 h
under similar Cu-catalyzed conditions, in presence/absence of
external oxidants. Some faint spots were observed on TLC,
which were not isolated. Assuming that alkenyl or alkynyl
substituted imidazo[1,2-a]pyridine might be formed as
intermediates in the reaction between 1a and 2a, compounds 7 or
8 were synthesized by standard procedures37,38 as model
substrates. Surprisingly 7 or 8 did not afford the dicarbonylated
product 3a, indicating that their formation is not involved in the
mechanism.
converted to super oxide radical F by oxygen insertion39a-b
.
Finally F gave the dicarbonylated product 3. To give further
confirmation to our proposed mechanism, the LC/HRMS of the
reaction mixture was recorded after 2 h. Presence of the peaks at
m/z 329.1378 and 357.1294 corresponding to the molecular
formula C22H21N2O [M+H]+ and C22H17N2O3 [M-Cu]+
respectively indicated the formation of intermediates C and F
(supporting information).
Scheme 5. Plausible mechanism
3. Conclusion
In summary we have demonstrated an inspirational direct C-3
sp2-H fictionalization of imidazoheterocycles by mean of
cleavage of two sp2-H and two sp3-H bonds between aryl
acetaldehyde and imidazoheterocycles, whereby oxidative cross-
dehydrogenative coupling and oxidation of methylene next to
phenyl group of aryl acetaldehydes proceeds in a cumulative
way. This copper catalyzed aerobic dual-oxidative cross
dehydrogenative methodology was applied for synthesis of 24
different varieties of imidazoheterocyclic diketones in moderate
to excellent yields. The methodology provides a straightforward,
high yielding and one-pot approach towards the synthesis of C-3
dicarbonylated imidazoheterocycles without prior activation of
C(sp2)-H or use of a base.
CuBr (10 mol%)
2,2'- bi pyridine (10 mol%)
TEMPO ( 3 equiv)
Toulene, 100°C
O
Air
N
H
N
N
Toulene, 100°C
O
N
O
Air
1a
2a
CuBr (10 mol%)
2,2'- bi pyridine (10 mol%)
Toulene, 100°C
3a
0%
N2
O
O
O
CuBr (10 mol%)
H
H
2,2'- bi pyridine (10 mol%)
Toulene, 100°C
Air 1atm
4. Experimental
4.1. General
2a
0%
N
H
O
CuBr (10 mol%)
N
N
2,2'- bi pyridine (10 mol%)
All the chemicals were purchased from Sigma-Aldich, Alfa
Aesar, and Spectrochem India Pvt. Ltd and used without further
purification. The solvents used were purchased from Merck
(India) and were distilled and dried before use. Nuclear magnetic
resonance spectra were recorded on Bruker 400 spectrometer. All
1H NMR experiments were reported in δ units, parts per million
(ppm), and were measured relative to residual chloroform (7.26
ppm) or DMSO (2.5 ppm) in the deuterated solvent. All 13C
NMR spectra were reported in ppm relative to deuterochloroform
(77.0 ppm) or [d6] DMSO (39.5 ppm). All coupling constants J
were reported in Hz. The following abbreviations were used to
describe peak splitting patterns when appropriate: s = singlet, d =
doublet, t = triplet, dd = doublet of doublet, m = multiplet and br
s = broad singlet. Melting points were determined on a capillary
point apparatus equipped with a digital thermometer and are
uncorrected. Mass spectra were recorded on Waters Synapt G2
high detection mass spectrometer at Core Instrumentation Centre,
University of Mysore.
N
O
TBHP (3 equiv.)
Toulene,100°C, 12 h
6
6a
0%
N
CuBr (10 mol%)
N
N
2,2'- bi pyridine (10 mol%)
N
or
O
N
O
N
Toulene,100°C, 20 h
Ph
3a
Ph
7
8
0%
Scheme 4. Control experiments
From the control experiments and literature reports,39-40 the
probable mechanism of the reaction could be described by the
attack of imidazo[1,2-a]pyridine (1) on carbonyl of phenyl
acetaldehyde (2) to give C, probably by radical mechanism in
presence of CuBr/O2 via single electron transfer41 (SET). This

5
4.2. General
imidazoheterocycles
Procedure
for
dicarbonylation
of
White solid; yield 82%; (171 mg, starting from 100 mg of
ACCEPTED MANUSCRIPT
1a); reaction time = 14 h; Rf = 0.46 (silica gel, 30% EtOAc-
Hexane); mp 137-140°C (lit. mp 138-140 °C) 29; H NMR (400
1
A mixture of imidazoheterocycles (0.52 mmol), phenyl
acetaldehyde (0.62 mmol), CuBr (0.052 mmol), 2,2-bipyridine
(0.052 mmol) in toluene (8 mL) was heated at 100 °C for 12-17
hrs (TLC). Toluene was evaporated and the reaction mixture was
directly subjected to silica gel column chromatography
(Hexane/EtOAc, 9:1) to yield the dicarbonylated product 3, 5 as
coloured products in pure form.
MHz, CDCl3) δ 9.81 (d, J = 6.9 Hz, 1H), 7.87 (d, J = 8.9 Hz,
1H), 7.72 – 7.66 (m, 1H), 7.57 (td, J = 8.7, 1.8 Hz, 4H), 7.29 (d, J
= 7.5 Hz, 3H), 7.26 (dd, J = 6.9, 1.1 Hz, 1H), 7.14 (t, J = 7.7 Hz,
2H) ppm; 13C NMR (100 MHz, CDCl3) δ 190.3, 183.8, 158.8,
148.5, 132.8, 132.2, 132.0, 131.2, 130.9, 130.0, 129.6, 129.6,
129.3, 128.1, 118.9, 117.7, 116.0 ; IR (KBr): 3067, 2932, 1676,
1590, 1400, 1254, 753 cm-1.
4.3. 1-Phenyl-2-(2-phenylimidazo[1,2-a]pyridin-3-yl)ethane-
1,2-dione (3a)
4.8. 1-(4-Fluorophenyl)-2-(2-phenylimidazo[1,2-a]pyridin-3-
yl)ethane-1,2-dione (3f)
Yellow solid; yield: 80%; (134 mg, starting from 100 mg of
Yellow solid; yield 85%; (151 mg, starting from 100 mg of
1a); reaction time = 12 h; Rf = 0.40 (silica gel, 30% EtOAc-
1a); reaction time = 13 h; Rf = 0.46 (silica gel, 30% EtOAc-
1
Hexane); mp 122-124 °C (lit. mp 122-123 °C)29; H NMR (400
1
Hexane); mp 165-167°C (lit. mp 165-168 °C) 29; H NMR (400
MHz, CDCl3) δ 9.78 (d, J = 6.7 Hz, 1H), 7.81 (d, J = 8.7 Hz,
1H), 7.65 (d, J = 7.7 Hz, 2H), 7.61 (d, J = 8.0 Hz, 1H), 7.51 (t, J
= 7.3 Hz, 1H), 7.33 (t, J = 7.5 Hz, 2H), 7.23 (d, J = 7.7 Hz, 2H),
7.20 (m, 2H), 7.03 (t, J = 7.4 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ 190.4, 183.6, 157.6, 147.3, 133.2, 132.4, 131.7, 130.1,
129.0, 128.6, 128.5, 128.3, 127.6, 127.0, 117.9, 116.7, 114.9; IR
(KBr): 2930, 2902, 1675, 1596, 1402, 1129, 859, 720 cm-1.
MHz, CDCl3) δ 9.83 (d, J = 6.7 Hz, 1H), 7.88 (d, J = 8.8 Hz,
1H), 7.83 – 7.73 (m, 2H), 7.73 – 7.66 (m, 1H), 7.32 (s, 1H), 7.30
(s, 3H), 7.15 (t, J = 7.5 Hz, 2H), 7.09 (t, J = 8.4 Hz, 2H) ppm; 13C
NMR (100 MHz, CDCl3) δ 189.8, 184.2, 167.6, 165.0, 158.7,
148.4, 132.9, 132.3, 132.2, 131.1, 130.1, 129.5, 129.3, 128.0,
118.0, 115.9; IR (KBr): 2943, 2816, 1666, 1582, 1400, 1233, 763
cm-1.
4.4. 1-(2-Phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-tolyl)ethane-
1,2-dione (3b)
4.9. 1-(Naphthalen-2-yl)-2-(2-phenylimidazo[1,2-a]pyridin-3-
yl)ethane-1,2-dione (3g)
Light Yellow solid; yield: 70%; (117 mg, starting from 100
Yellow solid; yield 76%; (147 mg, starting from 100 mg of
mg of 1a); reaction time = 13 h; Rf = 0.42 (silica gel, 30%
1a); reaction time = 14 h; Rf = 0.48 (silica gel, 30% EtOAc-
1
EtOAc- Hexane); mp 152-154 °C (lit. mp 152-155 °C)29; H
1
Hexane); mp 159-162 °C (lit. mp 158-162 °C)29; H NMR (400
NMR (400 MHz, CDCl3) δ 9.85 (d, J = 6.9 Hz, 1H), 7.87 (d, J =
8.9, 1H), 7.71 – 7.67 (m, 1H), 7.65 (d, J = 8.2 Hz, 2H), 7.33 (s,
1H), 7.32 (d, J = 1.3 Hz, 1H), 7.29 (dd, J = 7.4, 0.9 Hz, 1H), 7.26
(dd, J = 7.1, 1.2 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.15 – 7.10
(m, 2H), 2.43 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 191.1,
184.8, 158.6, 148.3, 145.3, 132.9, 131.0, 130.9, 130.0, 129.7,
129.4, 129.4, 127.9, 118.9, 117.6, 115.8, 21.9; IR (KBr): 3016,
1678, 1593, 1526, 1467, 1400, 1341, 730 cm-1.
MHz, CDCl3) δ 9.89 (d, J = 6.9 Hz, 1H), 8.37 (s, 1H), 7.93 – 7.85
(m, 3H), 7.82 (d, J = 8.6 Hz, 1H), 7.72 – 7.68 (m, 1H), 7.68 –
7.60 (m, 2H), 7.55 (dd, J = 11.1, 3.9 Hz, 1H), 7.34 – 7.28 (m,
2H), 7.28 – 7.24 (m, 1H), 7.24 – 7.20 (m, 1H), 7.02 (t, J = 7.7
Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 191.4, 184.6,
158.7, 148.4, 136.0, 133.0, 132.6, 132.3 ,131.1, 130.9, 130.0,
129.9, 129.4, 129.4, 129.2, 128.7, 127.9, 127.0, 124.0, 119.0,
117.7, 115.9; IR (KBr): 2939, 2844, 1625, 1609, 1409, 1228, 739
cm-1.
4.5. 1-(4-Methoxyphenyl)-2-(2-phenylimidazo[1,2-a]pyridin-
3-yl)ethane-1,2-dione (3c)
4.10. 1-(4-Chlorophenyl)-2-(2-(4-methoxyphenyl)imidazo[1,2-
a]pyridin-3-yl)ethane-1,2-dione (3h)
Brown solid; yield: 72%; (132 mg, starting from 100 mg of
1a); reaction time = 14 h; Rf = 0.42 (silica gel, 30% EtOAc-
Yellow solid; yield 78%; (136 mg, starting from 100 mg of
1h); reaction time = 15 h; Rf = 0.42 (silica gel, 30% EtOAc-
Hexane); mp 162-165 °C; 1H NMR (400 MHz, CDCl3) δ 9.80 (d,
J = 6.7 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 8.1 Hz,
2H), 7.66 (d, J = 8.6 Hz, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.23 (d, J
= 7.9 Hz, 3H), 6.65 (d, J = 8.3 Hz, 2H), 3.77 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 190.3, 183.9, 160.8, 158.8, 148.6,
140.7, 131.9, 131.5, 131.1, 130.9, 129.3, 129.0, 125.2, 118.8,
117.6, 115.8, 113.5, 55.3; IR (KBr): 3089, 2910, 1686, 1642,
1409, 1252, 895 cm-1; HRMS (ESI-TOF) (m/z) calculated
C22H16ClN2O3+ : 391.0849; found 391.0863 [M+H]+.
1
Hexane); mp 165-168 °C (lit. mp 166-168 °C)29; H NMR (400
MHz, CDCl3) δ 9.85 (d, J = 6.9 Hz, 1H), 7.86 (d, J = 8.9 Hz,
1H), 7.72 (d, J = 8.9 Hz, 2H), 7.70 – 7.64 (m, 1H), 7.38 – 7.31
(m, 2H), 7.26 (m, 2H), 7.14 (t, J = 7.6 Hz, 2H), 6.88 (d, J = 8.9
Hz, 2H), 3.90 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ
190.1, 185.0, 164.4, 158.5, 148.3, 133.0, 132.0, 130.8, 130.0,
129.3, 127.8, 126.7, 119.0, 117.6, 115.7, 113.9, 55.6; IR (KBr):
2930, 1658, 1599, 1460, 1260, 1180, 748, 753 cm-1
4.6. 1-(4-Chlorophenyl)-2-(2-phenylimidazo[1,2-a]pyridin-3-
yl)ethane-1,2-dione (3d)
4.11. 1-(2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-3-yl)-2-
phenylethane-1,2-dione (3i)
Yellow solid; yield 82%; (152 mg, starting from 100 mg of
1a); reaction time = 14 h; Rf = 0.44 (silica gel, 30% EtOAc-
1
Hexane); mp 122-125°C (lit. mp 120-125 °C) 29; H NMR (400
White solid; yield 75%; (121 mg, starting from 100 mg of 1i);
reaction time = 15 h; Rf = 0.45 (silica gel, 30% EtOAc- Hexane);
MHz, CDCl3) δ 9.81 (d, J = 6.7 Hz, 1H), 7.87 (d, J = 8.1 Hz,
1H), 7.68 (d, J = 8.1 Hz, 2H), 7.49 – 7.42 (m, 1H), 7.38 (d, J =
8.3 Hz, 2H), 7.31 (d, J = 7.5 Hz, 3H), 7.26 (s, 1H), 7.15 (t, J =
7.5 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 190.1, 183.9,
158.8, 148.5, 40.7, 131.8, 131.2, 130.9, 130.0, 129.6, 129.3,
129.0, 128.0, 118.9, 117.7, 116.0; IR (KBr): 2953, 2806, 1676,
1592, 1400, 1253, 753 cm-1.
1
mp 175-178 °C; H NMR (400 MHz, CDCl3) δ 9.85 (d, J = 6.9
Hz, 1H), 7.87 (d, J = 8.9 Hz, 1H), 7.78 – 7.73 (m, 2H), 7.72 –
7.67 (m, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H),
7.31 – 7.29 (m, 1H), 7.29 – 7.26 (m, 2H), 6.81 (t, J = 8.6 Hz, 2H)
ppm; 13C NMR (100 MHz, CDCl3) δ 191.5, 184.5, 164.7, 162.3,
157.5, 148.3, 134.4, 132.0, 132.0, 131.2, 129.5, 129.1, 129.7,
119.9, 117.6, 116.0, 115.1, 114.9; IR (KBr): 2983, 2890, 1686,
4.7. 1-(4-Bromophenyl)-2-(2-phenylimidazo[1,2-a]pyridin-3-
yl)ethane-1,2-dione (3e)

6
Tetrahedron
1624, 1409, 1382, 792 cm-1; HRMS (ESI-TOF) (m/z) calculated
2H), 2.53 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 190.4,
ACCEPTED MANUSCRIPT
C21H14FN2O2+ : 345.1039; found 345.1026 [M+H]+.
183.4, 157.1, 147.3, 135.8, 134.2, 132.1, 131.5, 131.3, 130.8,
129.9, 128.2, 127.3, 126.5,, 116.9, 18.5; IR (KBr): 3094, 2924,
4.12. 1-(4-Chlorophenyl)-2-(7-methyl-2-phenylimidazo[1,2-
a]pyridin-3-yl)ethane-1,2-dione (3j)
1674, 1620, 1409, 1396, 1273, 872 cm-1; HRMS (ESI-TOF) (m/z)
+
calculated C22H15BrClN2O2
: 453.0005; found 453.0018
[M+H]+.
Brown solid, yield 80%; (143 mg, starting from 100 mg of
1j); reaction time = 14 h; Rf = 0.48 (silica gel, 30% EtOAc-
Hexane); mp 178-180 °C; 1H NMR (400 MHz, CDCl3) δ 9.69 (d,
J = 7.0 Hz, 1H), 7.70 – 7.65 (m, 2H), 7.63 (s, 1H), 7.38 (d, J =
8.6 Hz, 2H), 7.30 (d, J = 0.7 Hz, 1H), 7.28 (s, 2H), 7.15 (dd, J =
10.1, 5.2 Hz, 2H), 7.10 (dd, J = 7.0, 1.6 Hz, 1H), 2.58 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ 190.3, 183.5, 159.1, 148.9,
143.2, 140.6, 133.0, 131.9, 130.8, 130.0, 129.5, 129.0, 128.5,
128.0, 118.3, 116.5, 21.8; IR (KBr): 3032, 2924, 1682, 1643,
1412, 1250, 903cm-1; HRMS (ESI-TOF) (m/z) calculated
C22H16ClN2O2+ : 375.0900; found 375.0923 [M+H]+.
4.17. 1-(4-Fluorophenyl)-2-(7-methyl-2-phenylimidazo[1,2-
a]pyridin-3-yl)ethane-1,2-dione (3o)
Yellow solid; yield 82%; (141 mg, starting from 100 mg of
1o); reaction time = 15 h; Rf = 0.46 (silica gel, 30% EtOAc-
Hexane); mp 191-192 °C; 1H NMR (400 MHz, CDCl3) δ 9.69 (d,
J = 6.9 Hz, 1H), 7.76 (dd, J = 8.1, 5.6 Hz, 2H), 7.62 (s, 1H), 7.29
(d, J = 7.4 Hz, 3H), 7.14 (t, J = 7.6 Hz, 2H), 7.07 (t, J = 8.7 Hz,
3H), 2.57 (s, 3H) ppm; 13C NMR (101 MHz, CDCl3) δ 190.0,
183.7, 167.5, 164.9, 159.1, 148.9, 143.1, 133.0, 132.3, 130.0,
129.5, 128.5, 127.9, 118.3, 116.5, 116.5, 115.8, 21.8; IR (KBr):
3032,1674, 1620, 1412, 1242, 903 cm-1; HRMS (ESI-TOF) (m/z)
calculated C22H16FN2O2+ : 359.1195; found 359.1206 [M+H]+.
4.13. 1-(7-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(p-
tolyl)ethane-1,2-dione (3k)
Brown solid; yield 72%; (122 mg, starting from 100 mg of
4.18. 1-(6-Bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-
phenylethane-1,2-dione (3p)
1k); reaction time = 15 h; Rf = 0.45 (silica gel, 30% EtOAc-
1
Hexane); mp 179-181 °C; H NMR (400 MHz, CDCl3) δ 9.70
(d, J = 7.0 Hz, 1H), 7.63 (s, 1H), 7.62 – 7.59 (m, 2H), 7.32 – 7.28
(m, 2H), 7.27 (s, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 7.7
Light yellow solid; yield 75%; (111 mg, starting from 100 mg
of 1p); reaction time = 15 h; Rf = 0.49 (silica gel, 30% EtOAc-
1
Hz, 2H), 7.08 – 7.05 (m, 1H), 2.56 (s, 3H), 2.42 (s, 3H) ppm; 13
C
Hexane); mp 152-154 °C (lit. mp 153-155 °C)29; H NMR (400
NMR (100 MHz, CDCl3) δ 191.3, 184.4, 158.9, 148.8, 145.2,
142.9, 133.0, 131.1, 130.0, 129.7, 129.4, 129.3, 128.5, 127.9,
MHz, CDCl3) δ 10.04 (t, J = 1.3 Hz, 1H), 7.75 (d, J = 1.3 Hz,
3H), 7.73 (d, J = 1.3 Hz, 1H), 7.63 – 7.58 (m, 1H), 7.42 (t, J = 7.8
Hz, 3H), 7.31 – 7.28 (m, 3H), 7.12 (t, J = 6.2 Hz, 2H) ppm; 13C
NMR (100 MHz, CDCl3) δ 191.1, 184.8, 158.6, 146.7, 134.3,
134.2, 133.2, 132.5, 130.0, 129.7, 129.6, 129.4, 128.7, 128.0,
118.9, 118.2, 110.6; IR (KBr): 3160, 2963, 2851, 1644, 1615,
1239, 678 cm-1.
118.7, 118.1, 116.4, 21.8; IR (KBr): 3032, 1682, 1597, 1412,
+
1250, 903cm-1; HRMS (ESI-TOF) (m/z) calculated C23H19N2O2
:
355.1446; found 355.1477 [M+H]+.
4.14. 1-(2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl)-2-
phenylethane-1,2-dione (3l)
4.19. 1-(7-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-
phenylethane-1,2-dione (3q)
Brown solid; yield 70%; (111 mg, starting from 100 mg of 1l);
reaction time = 15 h; Rf = 0.43 (silica gel, 30% EtOAc- Hexane);
1
mp 166-167 °C (lit. mp 166-168 °C)29; H NMR (400 MHz,
White solid; yield 72%; (118 mg, starting from 100 mg of
1q); reaction time = 15 h; Rf = 0.49 (silica gel, 30% EtOAc-
Hexane); mp 142-145 °C; 1H NMR (400 MHz, CDCl3) δ 9.71 (d,
J = 7.0 Hz, 1H), 7.73 (dd, J = 8.3, 1.1 Hz, 2H), 7.63 (s, 1H), 7.61
– 7.55 (m, 1H), 7.40 (t, J = 7.8 Hz, 2H), 7.32 – 7.29 (m, 2H),
7.28 – 7.24 (m, 1H), 7.13 – 7.07 (m, 3H), 2.57 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 191.6, 184.2, 159.0, 148.8, 143.0,
134.1, 133.5, 132.9, 130.0, 129.5, 128.5, 127.9, 118.7, 118.2,
116.4, 21.8; IR (KBr): 3018, 1690, 1598, 1471, 1345, 730 cm-1;
CDCl3) δ 9.84 (d, J = 6.8 Hz, 1H), 7.85 (d, J = 8.9 Hz, 1H), 7.79
– 7.74 (m, 2H), 7.70 – 7.65 (m, 1H), 7.58 (d, J = 7.4 Hz, 1H),
7.42 (t, J = 7.7 Hz, 2H), 7.26 (s, 1H), 7.23 (t, J = 2.7 Hz, 2H),
6.63 (d, J = 8.7 Hz, 2H), 3.76 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 191.6, 184.60, 161.0, 158.6, 148.4, 134.1, 133.4, 131.5,
131.0, 129.6, 129.3, 128.5, 125.1, 118.9, 117.5, 115.7, 113.5,
55.3; IR (KBr): 3060, 2933, 2751, 1684, 1615, 1239, 658 cm-1.
4.15. 1-(2-(3-Nitrophenyl)imidazo[1,2-a]pyridin-3-yl)-2-
phenylethane-1,2-dione (3m)
+
HRMS (ESI-TOF) (m/z) calculated C22H17N2O2 : 341.1290;
found 341.1317 [M+H]+.
White solid; yield 55%; (85 mg, starting from 100 mg of 1m);
reaction time = 15 h; Rf = 0.43 (silica gel, 30% EtOAc- Hexane);
mp 199-200 °C; H NMR (400 MHz, CDCl3) δ 9.85 (d, J = 6.8
4.20. 1-(2-(4-Chlorophenyl)-6-methylimidazo[1,2-a]pyridin-3-
yl)-2-(naphthalen-2-yl)ethane-1,2-dione (3r)
1
Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 8.04 (s, 1H), 7.89 (d, J = 8.9
Hz, 1H), 7.73 (t, J = 6.9 Hz, 4H), 7.61 (t, J = 7.4 Hz, 1H), 7.45
(d, J = 3.3 Hz, 1H), 7.42 (dd, J = 7.8, 3.7 Hz, 2H), 7.32 (t, J = 6.8
Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 191.4, 184.0,
155.6, 148.3, 147.2, 135.8, 134.9, 132.9, 131.5, 129.5, 129.4,
129.0, 125.1, 124.1, 119.1 117.9, 116.4; ; IR (KBr): 3078, 1674,
1589, 1404, 1250, 856 cm-1; HRMS (ESI-TOF) (m/z) calculated
C21H14N3O4+ : 372.0984; found 372.0998 [M+H]+.
Yellow solid; yield 74%; (129 mg, starting from 100 mg of
1r); reaction time = 15 h; Rf = 0.51 (silica gel, 30% EtOAc-
Hexane); mp 120-122 °C; 1H NMR (400 MHz, CDCl3) δ 9.72 (s,
1H), 8.34 (s, 1H), 7.92 – 7.85 (m, 3H), 7.76 (d, J = 9.0 Hz, 1H),
7.71 (dd, J = 8.6, 1.6 Hz, 1H), 7.68 – 7.62 (m, 1H), 7.57 (d, J =
7.9 Hz, 1H), 7.55 – 7.51 (m, 1H), 7.21 (d, J = 8.4 Hz, 2H), 7.00
(d, J = 8.4 Hz, 2H), 2.52 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 191.7, 184.2, 157.1, 147.3, 136.0, 135.6, 134.0, 132.5,
132.2, 131.6, 131.3, 130.8, 129.8, 129.3, 128.7, 128.0, 127.4,
127.1, 126.4, 123.8, 118.8, 116.9, 18.6; IR (KBr): 2942, 2856,
1628, 1612, 1411, 1228, 739 cm-1; HRMS (ESI-TOF) (m/z)
calculated C26H18ClN2O2+ : 425.1056; found 425.1033 [M+H]+.
4.16. 1-(4-Bromophenyl)-2-(2-(4-chlorophenyl)-6-
methylimidazo[1,2-a]pyridin-3-yl)ethane-1,2-dione (3n)
White solid; yield 77%; (143 mg, starting from 100 mg of
1n); reaction time = 15 h; Rf = 0.43 (silica gel, 30% EtOAc-
Hexane); mp 159-160 °C; H NMR (400 MHz, CDCl3) δ 9.64
(s, 1H), 7.77 (d, J = 9.0 Hz, 1H), 7.61 (dd, J = 8.4, 2.0 Hz, 4H),
7.58 – 7.54 (m, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz,
4.21. 1-(6-Bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-(4-
fluorophenyl)ethane-1,2-dione (3s)
1

7
4.26. 1-Phenyl-2-(2-phenylbenzo[d]imidazo[2,1-b]thiazol-3-
yl)ethane-1,2-dione (5c)
Yellow solid; yield 78%; (121 mg, starting from 100 mg of
ACCEPTED MANUSCRIPT
1s); reaction time = 15 h; Rf = 0.44 (silica gel, 30% EtOAc-
1
Hexane); mp 202-204 °C; H NMR (400 MHz, CDCl3+DMSO-
Light yellow solid; yield 68%; (104 mg, starting from 100 mg
of 4b); reaction time = 16 h; Rf = 0.56 (silica gel, 30% EtOAc-
Hexane); mp 177-178 °C; H NMR (400 MHz, CDCl3) δ 9.23
d6) δ 9.87 (s, 1H), 7.76 – 7.68 (m, 2H), 7.65 (dd, J = 8.6, 5.4 Hz,
2H), 7.22 (s, 1H), 7.16 (d, J = 7.1 Hz, 2H), 7.08 – 7.01 (m, 4H)
ppm; 13C NMR (100 MHz, CDCl3) δ 194.3, 189.0, 172.3, 169.7,
163.2, 151.5, 139.3, 137.3, 134.7, 134.5, 133.9, 132.7, 123.5,
123.0, 121.0, 120.7, 115.4; IR (KBr): 3132, 2950, 1674, 1612,
1481, 1412, 1250, 872 cm-1; HRMS (ESI-TOF) (m/z) calculated
C21H13BrFN2O2+ : 423.0144; found 423.0138 [M+H]+.
1
(dd, J = 8.5, 0.6 Hz, 1H), 7.81 (dd, J = 8.0, 0.9 Hz, 1H), 7.76 –
7.71 (m, 2H), 7.59 (m, 2H), 7.53 – 7.47 (m, 1H), 7.44 – 7.37 (m,
2H), 7.32 – 7.28 (m, 2H), 7.27 – 7.22 (m, 1H), 7.11 – 7.04 (m,
2H) ppm; 13C NMR (100 MHz, CDCl3) δ 191.4, 183.4, 160.6,
155.4, 134.2, 133.1, 133.3, 132.7, 130.3, 130.0, 129.6, 128.5,
127.9, 126.9, 126.0, 125.2, 123.8, 118.8; IR (KBr): 3158, 2950,
1697, 1645, 1239, 698 cm-1; HRMS (ESI-TOF) (m/z) calculated
C23H15N2O2S+ : 383.0854; found 383.0861 [M+H]+
4.22. 1-(2-(3-Methoxyphenyl)-7-methylimidazo[1,2-a]pyridin-
3-yl)-2-phenylethane-1,2-dione (3t)
White solid; yield 73%; (113 mg, starting from 100 mg of 1t);
reaction time = 15 h; Rf = 0.41 (silica gel, 30% EtOAc- Hexane);
mp 153-155°C; 1H NMR (400 MHz, CDCl3) δ 9.69 (s, 1H), 7.79
(d, J = 9.1 Hz, 1H), 7.77 – 7.74 (m, 2H), 7.59 – 7.53 (m, 2H),
7.42 (t, J = 7.8 Hz, 2H), 7.03 – 6.98 (m, 1H), 6.88 (dd, J = 7.5,
1.1 Hz, 1H), 6.84 – 6.79 (m, 2H), 3.54 (s, 3H), 2.53 (s, 3H) ppm;
13C NMR (100 MHz, CDCl3) δ 191.3, 184.4, 158.9, 158.3, 147.2,
134.2, 133.5, 129.5, 129.1, 128.6, 127.4, 126.2, 122.7, 118.7,
116.9, 116.4, 114.2, 54.9, 18.5; IR (KBr): 3132, 2948, 1674,
1614, 1481, 1250, 873 cm-1; HRMS (ESI-TOF) (m/z) calculated
C23H19N2O3+ : 371.1395; found 371.1364 [M+H]+.
Acknowledgments
The authors acknowledge Department of Science
&
Technology (DST), New Delhi for providing research grant
(SB/FT/CS-033/2012) for the work. We also thank BITS Pilani
for providing research grant (BITS Seed Grant) for the work. The
authors SMAS and DA thank UGC and DST, New Delhi, India
for providing BSR and JRF fellowship, respectively.
References and notes
4.23. 1-Phenyl-2-(2-(p-tolyl)imidazo[1,2-a]pyridin-3-
yl)ethane-1,2-dione (3u)
1. Bae, J. S.; Lee, D. W.; Lee, D. H.; Jeong, D. S. PCT Int. Appl.
WO2007011163A1, 2007.
2.
(a) Jain, A. N. J. Med. Chem. 2004, 47, 947-961. (b) Depoortere,
H.; George, P. US 5064836, 1991; (c) Harrison, T. S.; Keating, G.
M. CNS Drugs 2005, 19, 65-89; (d) Abe, Y.; Kayakiri, H.; Satoh,
S.; Inoue, T.; Sawada, Y.; Inamura, N.; Asano, M.; Aramori, I.;
Hatori, C.; Sawai, H.; Oku, T.; Tanaka, H. J. Med.Chem. 1998, 41,
4587-4598; (e) Almirante, L.; Polo, L.; Mugnaini, A.; Provinciali,
E.; Rugarli, P.; Biancotti, A.; Gamba, A.; Murmann, W. J. J. Med.
Chem. 1965, 8, 305-312.
(a) Kim, O.; Jeong, Y.; Lee, H.; Hong, S.-S.; Hong, S. J. Med.
Chem. 2011, 54, 2455-2466; (b) Kamal, A.; Reddy, J. S.;
Ramaiah, M. J.; Dastagiri, D.; Bharathi, E. V.; Sagar, M. V. P.;
Pushpavalli, S. N. C. V. L.; Ray, P.; Bhadra, M. P. Med. Chem.
Commun. 2010, 1, 355-360; (c) Frohn, M. J.; Hong, F. T.; Liu, L.;
Lopez, P.; Siegmund, A. C.; Tadesse, S.; Tamayo, N. Patent WO
2005070932, 2005; (d) Cheng, D.; Croft, L.; Abdi, M.; Lightfoot,
A.; Gallagher, T. Org. Lett. 2007, 9, 5175-5178; (e) Bode, M. L.;
Gravestock, D.; Moleele, S. S.; Westhuyzen, C. W. V.; Pelly, S.
C.; Steenkamp, P. A.; Hoppe, H. C.; Khan, T.; Nkabinde, L. A.
Bioorg. Med. Chem., 2011, 19, 4227-4237.
Yellow solid; yield 82%; (116 mg, starting from 100 mg of
1u); reaction time = 15 h; Rf = 0.41 (silica gel, 30% EtOAc-
Hexane); mp 109-110 °C (lit. mp 110 °C)29; 1H NMR (400 MHz,
CDCl3) δ 9.85 (d, J = 6.9 Hz, 1H), 7.86 (d, J = 8.9 Hz, 1H), 7.80
– 7.72 (m, 2H), 7.72 – 7.64 (m, 1H), 7.60 (t, J = 7.4 Hz, 1H),
7.42 (t, J = 7.8 Hz, 2H), 7.25 (td, J = 6.9, 1.0 Hz, 1H), 7.20 (d, J
= 8.0 Hz, 2H), 6.91 (d, J = 7.8 Hz, 2H), 2.29 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 191.5, 184.6, 158.9, 148.4, 139.5,
134.1, 133.5, 131.0, 129.9, 129.6, 129.3, 128.7, 118.9, 117.6,
115.7, 21.3 ; IR (KBr): 3065, 2921, 2841, 1674, 1605, 1229, 758
cm-1.
3.
4.24. 1-Phenyl-2-(2-phenylimidazo[1,2-a]pyrimidin-3-
yl)ethane-1,2-dione (5a)
White solid; yield 70%; (117 mg, starting from 100 mg of 4a);
reaction time = 17 h; Rf = 0.34 (silica gel, 30% EtOAc- Hexane);
mp 170- 171 °C (lit. mp 171 °C)29; 1H NMR (400 MHz, CDCl3) δ
10.07 (dd, J = 6.8, 1.8 Hz, 1H), 8.92 (dd, J = 4.1, 1.9 Hz, 1H),
7.76 (d, J = 7.4 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7
Hz, 2H), 7.38 (d, J = 7.3 Hz, 2H), 7.31 (dd, J = 9.4, 5.3 Hz, 2H),
7.13 (t, J = 7.6 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ
190.8, 185.3, 159.9, 154.9, 150.9, 136.9, 134.5, 133.0, 132.3,
130.0, 129.6, 128.7, 128.1, 117.2, 111.8; IR (KBr): 3068, 2924,
1682, 1595, 1493, 1392, 1347, 1138, 874, 685 cm-1.
4. Singhaus, R. R.; Bernotas, R. C.; Steffan, R.; Matelan, E.; Quinet,
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Kelly, S.; Owens, A. P.; Blackaby, W. P.; Lewis, R. T.; Stanley,
J.; Smith, A. J.; Ferris, P.; Sohal, B.; Cook, S. M.; Pike, A.;
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4.25. 1-Phenyl-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethane-
1,2-dione (5b)
Light yellow solid; yield 74%; (129 mg, starting from 100 mg
of 4b); reaction time = 16 h; Rf = 0.50 (silica gel, 30% EtOAc-
1
Hexane); mp 160-161 °C (lit. mp 160-162 °C)29; H NMR (400
MHz, CDCl3) δ 8.58 (d, J = 4.4 Hz, 1H), 7.78 (dd, J = 8.3, 1.2
Hz, 2H), 7.64 – 7.57 (m, 1H), 7.43 (dd, J = 10.8, 4.8 Hz, 2H),
7.33 (s, 1H), 7.31 (d, J = 1.3 Hz, 1H), 7.28 (dd, J = 6.2, 1.3 Hz,
1H), 7.17 (d, J = 4.4 Hz, 1H), 7.13 (t, J = 7.7 Hz, 2H) ppm; 13C
NMR (100 MHz, CDCl3) δ 191.7, 183.1, 158.6, 156.2, 134.4,
133.2, 132.7, 129.8, 129.6, 129.5, 128.7, 128.0, 122.0, 115.0; IR
(KBr): 3163, 2963, 2851, 1644, 1615, 1229, 658 cm-1.
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