H2O2/DMSO-Promoted Regioselective Synthesis of 3,3′-Bisimidazopyridinylmethanes via Intermolecular Oxidative C(sp2)-H Bond Activation of Imidazoheterocycles

Article abstract of DOI:10.1021/acs.joc.6b01355

In the past decade, metal-free approaches for C-C bond formation have attracted a great deal of attention due to their ease of use and low cost. This report represents a novel and metal-free synthesis of 3,3′-bisimidazopyridinylmethanes via intermolecular

Full text of DOI:10.1021/acs.joc.6b01355

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Article
H2O2/DMSO Promoted Regioselective Synthesis of
3,3#-Bisimidazopyridinylmethanes via Intermolecular
Oxidative C(sp2)-H Bond Activation of Imidazoheterocycles
Om P. S. Patel, Devireddy Anand, Rahul Kumar Maurya, and Prem Prakash Yadav
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01355 • Publication Date (Web): 03 Aug 2016
Downloaded from http://pubs.acs.org on August 4, 2016
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H2O2/DMSO
Promoted
Regioselective
Synthesis
of
3,3′ꢀ
5
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Bisimidazopyridinylmethanes via Intermolecular Oxidative C(sp2)ꢀH Bond
Activation of Imidazoheterocycles
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Om P. S. Patel,† Devireddy Anand,† Rahul K. Maurya,† Prem P. Yadav*,†
†Medicinal and Process Chemistry Division, CSIRꢀCentral Drug Research Institute, BSꢀ
10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
Eꢀmail: pp_yadav@cdri.res.in, ppy_cdri@yahoo.co.in
Table of Contents
ABSTRACT: In the past decade, metalꢀfree approaches for CꢀC bond formation have attracted a
great deal of attention due to their friendliness and inexpensiveness. This report represents a
novel and metalꢀfree synthesis of 3,3′ꢀbisimidazopyridinylmethanes via intermolecular oxidative
C(sp2)ꢀH bond functionalization of imidazo[1,2ꢀa]pyridines with dimethyl sulfoxide (DMSO) as
the carbon synthon (CH2) using H2O2 as a mild oxidant under air. A library of 3,3′ꢀbis(2ꢀ
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arylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methanes has been achieved in good to excellent yields. The
present methodology has been successfully applied to imidazo[2,1ꢀb]thiazoles and imidazo[2,1ꢀ
b]benzothiazoles. Furthermore, the current approach was also extended for the synthesis of
unsymmetrical 3,3′ꢀbisimidazopyridinylmethanes under optimized reaction conditions. A
mechanistic pathway is proposed based on experiments with radical scavengers, DMSOꢀd6 and
ESIꢀMS observations.
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INTRODUCTION
Dimethyl sulfoxide (DMSO) has been extensively employed as a solvent in organic synthesis
due to its rather low cost, relative stability and low toxicity. Besides being an effective polar
medium, DMSO is also used as a substrate and synthon in organic transformations.1 An
abundance of recent reports has shown that it has been used as a source of –O, ꢀSMe, ꢀCH2SMe,
ꢀSO2Me, ꢀMe, ꢀCN, ꢀCHO and CH2 as a functional unit inserted into target molecules.1
Currently, our interest is focussed on the functionalization of heteroarenes (imidazoheterocycles)
by using DMSO as a carbon synthon. Imidazo[1,2ꢀa]pyridines and its derivatives are important
structural units found in various natural products and pharmaceuticals such as zolpidem,
alpidem, zolimidine, olprinone, saripidem, and necopidem (Figure 1).2 Therefore, several
methodologies have been developed for the preparation and postꢀtransformation of imidazo[1,2ꢀ
a]pyridines and related imidazo[1,2ꢀa]heterocycles.2,3 Due to the electron rich nature of Cꢀ3
position of imidazo[1,2ꢀa]pyridine, several synthetic methods have emerged for oxidative CꢀH
bond functionalization at Cꢀ3 position regioselectively.3 Very recently, three similar reports were
developed for the synthesis of 3,3′ꢀbisimidazopyridinylmethanes.4 (i) The Sun group successfully
realized a H3PO4ꢀpromoted synthesis of bis(imidazo[1,2ꢀa]pyridinꢀ3ꢀyl)methanes using DMSO
as the methylene source (Scheme 1, a).4a The reaction proceeds through ionic mechanistic
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pathway via in situ formation of formaldehyde. (ii) Patel et. al., reported a copperꢀcatalyzed
approach to synthesize similar target compounds using dimethylacetamide (DMA) as the carbon
synthon (Scheme 1, b).4b (iii) Kumar and coꢀworkers also developed a vanadyl acetylacetonateꢀ
catalyzed methylenation of imidazo[1,2ꢀa]pyridines by using DMA as a methylene source
(Scheme 1, c).4c A similar strategy was developed by Cui et al., to synthesize 3,3′ꢀ
diindolylmethane via palladium catalyzed postꢀfunctionalization strategy using DMSO as the
methylene source.5 Despite having a few valuable advantages, these reactions suffer from certain
limitations such as the use of metal catalysts,4b,c,5 inorganic acid,4a base and inert atmosphere5 to
catalyze the reaction via an ionic mechanistic pathway.
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Figure 1. Representative examples of anxiolytic drugs and bioactive agents.2
In continuation of our research program for the development of mild and efficient approaches for
CꢀH bond functionalization,6 herein, we report a unique approach for the synthesis of bis(2ꢀ
arylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methanes via C(sp2)ꢀH bond activation by using H2O2 as a mild
oxidant and DMSO as the carbon source. The present protocol represents a facile transformation
for the construction of 3,3′ꢀbisimidazopyridinylmethanes under metalꢀfree and aerobic conditions
and provided a practical yield.
Scheme 1. Recent reports for Cꢀ3 functionalization of imidazo[1,2ꢀa]pyridines
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Previous Reports
Ref: 4a
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N
H3PO4 (3 equiv.)
N
N
a)
R
DMSO (6 equiv.)
Toluene, 115 °C, 24 h
N
N
N
R = Alkyl, Ar, Het Ar
R
R
9
Ionic mechanism
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via in situ formation of HCHO
Ref: 4b
N
Cu(OAc)2 (20 mol%)
N
R
N
b)
N
K2S2O8 (2 equiv.)
DMA, 120 °C, 6-12 h
Ionic mechanism
N
N
R
R
R = Alkyl, Ar, Het Ar
Ref: 4c
N
VO(acac)2 (10 mol%)
N
R
N
c)
N
IBD (2 equiv.)
DMA, 100-150 °C, 6 h
N
N
R
R
R = Ar
Ionic mechanism
This Work
H
H
30% Aq. H2O2
N
N
N
d)
R
DMSO
, 125 °C, 12-24 h
N
N
N
R
R
* Free radical mechanism
* Metal, ligand and additive free protocol
* Broad substrate scope
R = Ar, Het Ar
RESULTS AND DISCUSSION
The oxidative coupling reaction condition was optimized using 2ꢀphenylꢀimidazo[1,2ꢀa]pyridine
(1a) as the model substrate. The reaction was initially performed in DMSO at 125 °C under air
without the use of any external oxidant. The respective product 2a was formed in 37% yield in
24 h (Table 1, entry 1) and the structure was unambiguously confirmed by 1D, 2D NMR
spectroscopy and HRMS analysis (Supporting Information). The initial result prompted us to
optimize the reaction conditions to enhance the yield of desired product 2a. In this perspective, a
series of external oxidants namely TBHP, DTBP, TBPB, H2O2 and oxone (3 equiv. each) were
employed under identical reaction conditions (Table 1, entries 2ꢀ6). Pleasingly, only H2O2 (3
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equiv.) provided the product with 68% yield in 24 h (Table 1, entry 5), whereas, other oxidants
were found to diminish the yield of 2a. It was noticed that in the case of TBHP, DTBP, and
TBPB, the reaction produced a complex mixture of products. From this complex mixture the Cꢀ3
formylated product, 2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀcarbaldehyde (4a), was isolated in 13%,
30% and <5% yields, respectively. By increasing the equiv. of TBHP and DTBP (5 equiv. each)
in the reaction, 4a was formed in an enhanced yield of 22% and 50% respectively, without
formation of desired product 2a (Table 1, entries 7 and 8). The difference in the course of
reaction of peroxide oxidants (H2O2 vs. TBHP/DTBP) may be due to the in situ formation of
tertꢀbutoxyl and tertꢀbutylperoxy radicals in the case of TBHP/DTBP7, which leads to Cꢀ3
formylation instead of coupling with another mole of 2ꢀphenylimidazo[1,2ꢀa]pyridine (1a).
However, in the case of H2O2 (●OH) the methylated intermediate undergoes a sequence of
hydrogen atom abstraction followed by radical coupling of 1a to afford the desired final product
2a. Further, an increase in the amount of H2O2 concentration to 5 equiv. facilitated the product
2a with 82% yield in 18 h (Table 1, entry 10). On decreasing the reaction temperature to 80 °C
from 125 °C, the corresponding product 2a was formed in 11% yield with 80% recovery of 1a
(Table 1, entry 11). No significant enhancement in the yield of 2a was observed by increasing
the H2O2 loading to 6 equiv. in the reaction (Table 1, entry 12).
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Table1. Optimization of the Reaction Conditionsa
Entry Oxidant (equiv.)
Solvent (10 mL) Time (h)
Yield (%)b
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1
2
ꢀ
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
24
24
24
24
24
24
18
18
12
18
20
18
37
0c
0d
0e
TBHP (3)
DTBP (3)
TBPB (3)
H2O2 (3)
Oxone (3)
TBHP (5)
DTBP (5)
H2O2 (5)
H2O2 (5)
H2O2 (5)
H2O2 (6)
3
4
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5
68
6
0
0f
7
8
0g
71
82
11h
81
9
10
11
12
aReaction conditions: 1a (1 equiv.), oxidant (3ꢀ5 equiv.) in 10 mL of DMSO at 125 °C. Isolated yield. 2ꢀ
phenylimidazo[1,2ꢀa]pyridineꢀ3ꢀcarbaldehyde (4a) was formed in 13% yield. d4a was formed in 30% yield. e4a was
b
c
f
g
h
formed in <5% yield. 4a was formed in 22% yield. 4a was formed in 50% yield. Reaction performed at 80 °C.
TBHP = tertꢀbutyl hydroperoxide (70% aq. Solution), DTBP = diꢀtertꢀbutyl peroxide, TBPB = tertꢀbutyl
peroxybenzoate, DMSO = dimethyl sulfoxide.
Having optimized reaction conditions in hand (Table 1, entry 10), the utility of present approach
was systematically investigated by introducing substrates bearing a wide variety of functional
groups (electronꢀwithdrawing and electronꢀdonating groups) on the Cꢀ2 aryl ring and pyridine
ring of imidazo[1,2ꢀa]pyridine (Scheme 2). At first, the effect of electronꢀwithdrawing
substituents (4ꢀCl, F, Br, and CN) on the Cꢀ2 aryl ring of imidazo[1,2ꢀa]pyridine was examined.
All the corresponding products (2aꢀ2e) were formed in good to excellent yields (75%ꢀ82%). In
the case of CF3 present on meta position of the aryl ring, only 51% yield of 2f was obtained,
perhaps due to the deactivation of Cꢀ3 position by the strong electronꢀwithdrawing nature of CF3
group. Next, the effect of electronꢀdonating groups (pꢀCH3 and pꢀOCH3) present on the aryl ring
of imidazo[1,2ꢀa]pyridine was studied. The respective products 2g and 2h were obtained in
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excellent yields (84% and 92%, respectively), representing a relatively better yield compared to
the electronꢀneutral 2ꢀphenylꢀimidazo[1,2ꢀa]pyridine under identical reaction conditions.
Next, the electronic effects of substituents (R2= EWGs and EDGs) on the pyridine ring of
imidazo[1,2ꢀa]pyridine at different positions were studied. Interestingly, substrates bearing
electronꢀwithdrawing substituents such as 5ꢀBr, 5ꢀI and 5,7ꢀdi Cl on the pyridine ring of
imidazo[1,2ꢀa]pyridine smoothly underwent in the reaction and yielded the corresponding
products (2i, 2j, and 2k, respectively) in moderate to good yields (55%ꢀ67%). It is worth noting
that halogens (F, Cl, Br, and I) and ꢀCN groups are tolerated under optimized conditions and may
serve as crucial substituents for postꢀfunctionalization reactions. Further, employing the substrate
bearing 5ꢀCl and pꢀBr on pyridine ring and aryl ring of imidazo[1,2ꢀa]pyridine, respectively,
furnished the desired product 2l in 65% yield. On the other hand, substrates containing electronꢀ
donating groups (6ꢀCH3 and 5ꢀCH3) present on the pyridine ring of imidazo[1,2ꢀa]pyridine
smoothly participated in the reaction and provided the corresponding products 2m and 2n in high
yields under optimized reaction conditions. The substrate bearing electronꢀdonating groups such
as 6ꢀEt and pꢀOCH3 present on pyridine and aryl ring of imidazo[1,2ꢀa]pyridine, respectively,
facilitated the desired product 2o in about 86% yield. The reaction of heteroꢀarene (thiophene) at
the Cꢀ2 position of imidazo[1,2ꢀa]pyridine was also carried out. To our delight, the respective
product bis(2ꢀ(thiophenꢀ2ꢀyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2p) was obtained in 60%
yield. However, substrates bearing CF3, tertꢀbutyl, and H at Cꢀ2 position of imidazo[1,2ꢀ
a]pyridine failed to deliver the corresponding products 2qꢀ2s under identical reaction conditions,
indicating that aryl substitution at Cꢀ2 position is necessary for the reaction to proceed.8
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Scheme 2. Substrate Scope of Imidazo[1,2ꢀa]pyridinea,b
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R2
N
R2
N
N
N
N
1
30% Aq. H2O2 (5 equiv.)
R2
R1
N
DMSO,
125 °C, 12-24 h
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R1
R1
2
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
F
N
N
Cl
F
Br
2d (78%, 18 h)
NC
2e (79%, 15 h)
Cl
Br
CN
2a (82%, 18 h)
2b (80%, 19 h)
2c (75%, 17 h)
Br
Br
I
I
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
F3C
F3C
H3CO
H3C
2g (84%, 16 h)
OCH3
CH3
2f (51%, 22 h)
2i (66%, 17 h)
2j (55%, 23 h)
2h (92%, 15 h)
H3C
CH3
Cl
Cl
H3C
N
Cl
CH
CH3
3
CH3
Cl
Cl
Cl
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Br
H3CO
OCH3
2o (86%, 16 h)
Br
2m (76%, 15 h)
2k (67%, 20 h)
2n (80%, 16 h)
2l (65%, 18 h)
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
S
S
F3C
CF3
2p (60%, 21 h)
2q (0%, 24 h)
2r (0%, 24 h)
2s (0%, 24 h)
aAll reactions were performed by using 1 (1 equiv., 300 mg) and 30% aq. H2O2 (5 equiv.) in 10 mL of DMSO at 125
°C for 12ꢀ24 h. bIsolated yields.
The scope of the present protocol was further elaborated with other imidazoheterocycles like
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imidazo[2,1ꢀb]thiazole and imidazo[2,1ꢀb]benzothiazole to the reaction condition (Scheme 3).
Gratifyingly, substrates bearing electronꢀwithdrawing (pꢀCl and pꢀF) and electronꢀdonating
groups (p–CH3) present on the aryl ring of imidazo[2,1ꢀb]thiazole and imidazo[2,1ꢀ
b]benzothiazole were wellꢀtolerated in the reaction and furnished the corresponding products in
good to excellent yields (Scheme 3, entries 2tꢀ2y). We also tried the reaction of 1ꢀmethylꢀ2ꢀ
phenylꢀ1Hꢀindole (1z) under optimal reaction conditions. However, the reaction failed to furnish
the respective product 2z.
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Scheme 3. Substrate Scope of Other Heterocyclesa,b
S
S
N
N
30% Aq. H2O2 (5 equiv.)
N
N
N
S
N
R3
DMSO,
125 °C, 12-24 h
1
R3
S
R3
2
S
S
S
S
S
S
S
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Cl
Cl
F
H3C
2w (90%, 12 h)
CH3
F
2t (88%, 15 h)
2u (84%, 16 h)
2v (83%, 12 h)
S
S
S
S
N
N
N
N
N
N
N
N
N
N
CH3
H3C
2x (65%, 22 h)
2z (0%, 24 h)
2y (68%, 24 h)
aReaction conditions similar to Scheme 2. bIsolated yields
Furthermore, the scope of present method was extended for the synthesis of unsymmetrical 3,3′ꢀ
bisimidazopyridinyl compounds under optimized reaction conditions. The crossꢀcoupling
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reaction of various substituents present on the Cꢀ2 aryl ring (ꢀCl, ꢀBr, and –OCH3) and pyridine
ring (ꢀCl, ꢀdichloro, and –Br) of imidazoheterocycles were amenable to the reaction condition
and afforded the respective unsymmetrical products (3al, 3hk, 3hi, and 3hu) in good yields
compared to corresponding symmetrical products (Scheme 4).
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Scheme 4. Substrate Scope of Unsymmetrical Imidazoheterocyclesa,b
R2
N
N
N
R
N
N
30% Aq. H2O2 (5 equiv.)
N
1
′
2
+ 2
+
+
DMSO,
Symmetrical
125 °C, 17-23 h
3
N
R1
R2
R1
R
N
Unsymmetrical
′
1
Entry (Product)
Time
Yields (%)b
23 h
20 h
16, 31, 13
19, 29, 14
19 h
17 h
20, 27, 11
21, 35, 18
S
N
N
N
N
2h
+
+
2u
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aReaction was performed by using 1 (1 equiv.), 1′ (1 equiv.) and 30% aq. H2O2 (5 equiv.) in 10 mL of DMSO at 125
°C for 17ꢀ23 h. bIsolated yields of each products.
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To gain an insight into the mechanism of the oxidative coupling reaction, a series of control
experiments were performed. The isotopic labeling experiment was carried out using 1a in the
presence of DMSOꢀd6 under the optimized reaction conditions. The deuterated product 2aA was
formed in 78% yield with more than 99% incorporation of deuterium (Scheme 5, eq 1). This
study clearly indicated that DMSO is a source of oneꢀcarbon synthon. Mass spectrometric
analysis of crude reaction mixture after 18 h revealed the presence of methylated intermediate
(B′), which showed a [M + H]+ peak at 212 da (Scheme 5, eq I). To detect the kind of
mechanism involved in this transformation, well known radical scavengers, such as TEMPO
(2,2,6,6ꢀtetramethylpiperidine 1ꢀoxy) and BHT (butylated hydroxytoluene) were added to the
reaction (Scheme 5, eq II and III). The product formation was completely inhibited, suggesting
an involvement of radicalꢀmediated pathway. To further confirm the mechanistic pathway, the
reaction of the 3ꢀmethylꢀ2ꢀphenylimidazo[1,2ꢀa]pyridine (B) with 1a was carried out in DMF
under standard reaction conditions. The respective product 2a was formed in 61% yield (Scheme
5, eq IV). These experiments together with ESIꢀMS observation confirm that the reaction may
proceed via formation of methylated intermediate B.
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In accordance with the preliminary mechanistic studies and literature precedents9, a proposed
mechanistic pathway is depicted as shown in Scheme 6. Initially, the hydroxyl radical generated
through homolytic cleavage of H2O2 and subsequently reacts with DMSO to produce methyl
radical species.9aꢀc The methyl radical reacts with 1a to afford the radical intermediate A, which
could be stabilized by the adjacent phenyl ring. The radical intermediate A leads to methylated
intermediate B via •H abstraction by hydroxyl radical with subsequent loss of H2O. The hydroxyl
radical subsequently abstracts •H from B to form the radical intermediate C with the removal of
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H2O. The intermediate C reacts with another mole of 1a to afford the radical intermediate D,
which upon subsequent loss of H2O in the presence of hydroxyl radical delivers the
corresponding final product 2a.
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Scheme 5. Preliminary Mechanistic Studies
Scheme 6. Plausible Mechanistic Pathway
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H2O2
Homolytic cleavge
6
7
8
9
OH
S
OH
O
S
O
S
H3C
CH3
CH3
+
H3C
N
OH
H3C
CH3
O
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OH
H
CH3
N
N
Ph
Ph
Ph
N
N
B
N
H2O
A
1a
OH
H2O
OH
1a
H
N
N
N
N
N
Ph
N
N
N
N
N
Ph
Ph
D
Ph
Ph
2a
H2O
C
CONCLUSION
In Summary, we have developed a facile, transition metalꢀfree and regioselective approach for
the synthesis of 3,3′ꢀbisimidazopyridinylmethanes using DMSO as the methylene source. The
radical mechanism was established by experiments with radical scavengers (TEMPO and BHT),
DMSOꢀd6 and ESIꢀMS analysis. The use of mild oxidant H2O2 to activate Cꢀ(sp2)ꢀH/C(sp3)ꢀH in
a cascade manner under aerobic conditions to furnish symmetrical and unsymmetrical products
in good to excellent yields are attractive features of this approach. Moreover, further applications
of this approach are ongoing in our laboratory.
EXPERIMENTAL SECTION
General information
Melting points were determined on a capillary melting point apparatus and are uncorrected. All
1
13
the compounds were fully characterized by H, C, IR, and further confirmed through ESIꢀMS
and HRMS analysis. 1H NMR spectra were recorded on 400 and 500 MHz in CDCl3, DMSOꢀd6
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and 13C NMR spectra recorded on 100 and 125 MHz in CDCl3, DMSOꢀd6, CD3OD and TFA
using TMS as an internal standard. Multiplicities are reported as follows: singlet (s), doublet (d),
broad singlet (br s), doublet of doublets (dd), triplet (t), doublet of doublet of doublet (ddd),
doublet of triplet (dt), and multiplet (m). Chemical shift (δ) and coupling constants (J) are
reported in parts per million (ppm) relative to the residual signal of TMS in deuterated solvents
and hertz, respectively. IR spectra were recorded using an FTꢀIR spectrophotometer, and values
are reported in cmꢀ1. HRMS were recorded using a QꢀTOF mass spectrometer. Column
chromatography was performed over silica gel (60ꢀ120 mesh) using EtOAcꢀnꢀhexane as an
eluent. All chemicals and reagents were purchased from commercial sources and used without
further purification.
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General experimental procedure for the preparation of starting materials (1). The starting
material 2ꢀarylimidazo[1,2ꢀa]pyridines 1aꢀ1y (known compounds)10,11 and 1o (unknown) were
prepared by a known literature procedure.11
Experimental procedure for the synthesis of symmetrical compounds 2aꢀ2z. To a wellꢀ
stirred solution of substrate (1) (300 mg, 1 equiv.) in DMSO (10 mL) placed into a 50 mL,
roundꢀbottom flask was added 30% aq. H2O2 (5 equiv.) at room temperature. The resulting
mixture was heated at 125 °C for 12ꢀ24 h. After completion of the reaction monitored by TLC,
the reaction mixture was allowed to stand at room temperature for 30 minutes. Then the mixture
was with 20 mL of H2O and extracted with EtOAc (3 x 50 mL) followed by washing with brine
(10 mL) and dried over Na2SO4. After evaporation of the solvent under reduced pressure, the
crude product was purified by silica gel (60ꢀ120 mesh) column chromatography eluted with
EtOAc and nꢀhexane (8:2 to 1:9) to afford the respective products (2).
Experimental procedure for the synthesis of unsymmetrical compounds (3). To a wellꢀ
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stirred solution of substrate 1 (300 mg, 1 equiv.) and 1′ (1 equiv.) in DMSO (10 mL) placed into
a 50 mL, roundꢀbottom flask was added 30% aq. H2O2 (5 equiv.) at room temperature. The
resulting mixture was heated at 125 °C for 17ꢀ23 h. After completion of the reaction monitored
by TLC, the reaction mixture was allowed to stand at room temperature for 30 minutes. Then the
mixture was mixed with 20 mL of H2O and extracted with EtOAc (3 x 50 mL) followed by
washing with brine (10 mL) and dried over Na2SO4. After evaporation of the solvent under
reduced pressure, the crude product was purified by silica gel (60ꢀ120 mesh) column
chromatography eluted with EtOAc and nꢀhexane (8:2 to 1:9) to afford respective products 2, 3
and 2′.
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Bis(2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2a). White solid (255 mg, 82%); mp
216ꢀ218 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3684, 3019, 1602, 1520, 1476, 1334, 1072, 928, 848, 627,
493; δH (400 MHz; CDCl3) = 7.78 (4H, dd, J = 8.4, 1.4 Hz), 7.53ꢀ7.49 (6H, m), 7.44ꢀ7.40 (2H,
m), 7.33 (2H, d, J = 6.9 Hz), 7.04 (2H, m), 6.46 (2H, td, J = 6.8, 1.2 Hz), 4.99 (2H, s) ppm; δC
(100 MHz; CDCl3) = 145.1 (2xC), 144.3 (2xC), 134.4 (2xC), 129.01 (4xCH), 128.9 (4xCH),
128.3 (2xCH), 124.3 (2xCH), 123.8 (2xCH), 117.5 (2xCH), 114.3 (2xC), 112.3 (2xCH) 19.8
(CH2) ppm; HRMS (ESI): Calcd for C27H21N4 [M + H]+ 401.1766, Found: 401.1755.
Bis(2ꢀ(4ꢀchlorophenyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2b). White solid (195 mg,
80%); mp 270ꢀ272 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3683, 3019, 1636, 1522, 1476, 1404, 1022, 928,
669, 626; δH (400 MHz; CDCl3) = 7.64 (4H, dt, J = 9, 2.4 Hz), 7.54 (2H, dt, J = 9.0, 1.0 Hz),
7.43 (4H, dt, J = 9.0, 2.4 Hz), 7.38 (2H, dt, J = 6.9, 1.0 Hz), 7.10 (2H, ddd, J = 9, 6.8, 1.2 Hz),
6.55 (2H, td, J = 6.8, 1.2 Hz), 4.90 (2H, s) ppm; δC (100 MHz; CDCl3) = 145.1 (2xC), 143.2
(2xC), 134.3 (2xC), 132.7 (2xC), 130.0 (4xCH), 129.0 (4xCH), 124.7 (2xCH), 123.5 (2xCH),
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117.7 (2xCH), 114.1 (2xC), 112.7 (2xCH), 20.1 (CH2) ppm; HRMS (ESI): Calcd for
C27H19Cl2N4 [M + H]+ 469.0987, Found: 469.0976.
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Bis(2ꢀ(4ꢀfluorophenyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2c). White solid (231 mg,
75%); mp 190ꢀ192 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3745, 3391, 3019, 1637, 1517, 1403, 1047, 928,
669; δH (400 MHz; CDCl3) = 7.69ꢀ7.66 (4H, m), 7.52 (2H, dd, J = 9.0, 0.1 Hz), 7.38ꢀ7.36 (2H,
m), 7.17ꢀ7.06 (6H, m), 6.54 (2H, t, J = 6.8 Hz), 4.88 (2H, s) ppm; δC (125 MHz; CDCl3) = 162.8
(JCꢀF = 246.2, 2xC), 145.0 (2xC), 143.4 (2xC), 130.5 (JCꢀF = 8.7 Hz, 4xCH), 130.3 (JCꢀF = 2.5 Hz,
2xC), 124.5 (2xCH), 123.5 (2xCH), 117.6 (2xCH), 115.8 (JCꢀF = 21.2, 4xCH), 113.9 (2xC),
112.6 (2xCH), 20.0 (CH2) ppm; HRMS (ESI): Calcd for C27H19F2N4 [M + H]+ 437.1578, Found:
437.1566.
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Bis(2ꢀ(4ꢀbromophenyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2d). White solid (239 mg,
78%); mp 274ꢀ276 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3390, 3019, 1638, 1402, 1215, 1070, 768, 668;
δH (400 MHz; CDCl3) = 7.58 (8H, s), 7.54 (2H, dt, J = 9.1, 1 Hz), 7.37 (2H, dd, J = 5.9, 1 Hz),
7.10 (2H, ddd, J = 9.0, 6.8, 1.2 Hz), 6.56 (2H, td, J = 6.8, 1.2 Hz), 4.88 (2H, s) ppm; δC (100
MHz; CDCl3) = 145.1 (2xC), 143.2 (2xC), 133.1 (2xC), 131.9 (4xCH), 130.2 (4xCH), 124.7
(2xCH), 123.5 (2xCH), 122.5 (2xC), 117.7 (2xCH), 114.1 (2xC), 112.8 (2xCH), 20.1 (CH2)
ppm; HRMS (ESI): Calcd for C27H19Br2N4 [M + H]+ 558.9956, Found: 558.9955.
Bis(2ꢀ(4ꢀcyanophenyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2e). White solid (243 mg,
79%); mp 295ꢀ297 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3401, 3019, 1635, 1385, 1216, 1070, 669; δH
(400 MHz; CDCl3) = 7.69 (4H, d, J = 8.2 Hz), 7.63 (4H, d, J = 8.2 Hz), 7.57 (2H, d, J = 9.1 Hz),
7.47 (2H, d, J = 6.9 Hz), 7.19 (2H, t, J = 6.9 Hz), 6.68 (2H, t, J = 6.8 Hz), 4.89 (s, 2H) ppm; δC
(100 MHz; CDCl3 + CD3OD) = 145.2 (2xC), 142.3 (2xC), 138.5 (2xC), 132.1 (4xCH), 128.9
(4xCH), 125.5 (2xCH), 123.1 (2xCH), 118.5 (2xC), 117.8 (2xCH), 114.5 (2xC), 113.4 (2xCH),
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111.7 (2xC), 20.4 (CH2) ppm; HRMS (ESI): Calcd for C29H19N6 [M + H]+ 451.1671, Found:
451.1663.
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Bis(2ꢀ(3ꢀ(trifluoromethyl)phenyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2f). White solid
(157 mg, 51%); mp 186ꢀ188 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3853, 3745, 3392, 3019, 1638, 1403,
1050, 929, 669; δH (400 MHz; CDCl3) = 7.94 (2H, s), 7.75 (2H, d, J = 7.6 Hz), 7.61 (2H, d, J =
7.6 Hz), 7.56ꢀ7.49 (4H, m), 7.43 (2H, d, J = 6.9 Hz), 7.14 (2H, td, J = 7.9, 0.1 Hz), 6.64ꢀ6.61
(2H, m), 4.89 (2H, s) ppm; δC (125 MHz; CDCl3) = 145.1 (2xC), 143.0 (2xC), 135.0 (2xC),
131.7 (2xCH), 131.2 (2xC, q, JCꢀF = 32.5 Hz), 129.0 (2xCH), 125.6 (2xCH, br q, JCꢀF = 3.7 Hz),
125.0 (2xCH), 124.9 (2xCH, br q, JCꢀF = 3.7 Hz), 123.3 (2xCH), 117.8 (2xCH), 114.2 (2xC),
113.0 (2xCH), 20.2 (CH2) ppm; HRMS (ESI): Calcd for C29H19F6N4 [M + H]+ 537.1514,
Found: 537.1509.
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Bis(2ꢀpꢀtolylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2g). Yellow solid (259 mg, 84%);
mp 255ꢀ257 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3400, 3019, 1634, 1385, 1215, 1070, 769, 669; δH
(400 MHz; CDCl3) = 7.69 (4H, d, J = 8.0 Hz), 7.51 (2H, d, J = 9.0 Hz), 7.33 (6H, br t, J = 7.6
Hz), 7.03 (2H, t, J = 7.8 Hz), 6.45 (2H, t, J = 6.8 Hz), 4.98 (2H, s), 2.44 (s, 6H) ppm; δC (100
MHz; CDCl3) = 145.0 (2xC), 144.3 (2xC), 138.1 (2xC), 131.5 (2xC), 129.6 (4xCH), 128.9
(4xCH), 124.2 (2xCH), 123.9 (2xCH), 117.4 (2xCH), 114.2 (2xC), 112.2 (2xCH), 21.4
(2xCH3), 19.9 (CH2) ppm; HRMS (ESI): Calcd for C29H25N4 [M + H]+ 429.2079, Found:
429.2069.
Bis(2ꢀ(4ꢀmethoxyphenyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2h). White solid (296 mg,
92%); mp 214ꢀ216 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3682, 3391, 3019, 1614, 1474, 1032, 928, 669,
627; δH (400 MHz; CDCl3) = 7.74ꢀ7.70 (4H, m), 7.50 (2H, d, J = 9.0 Hz), 7.35 (2H, d, J = 6.9
Hz), 7.06ꢀ7.0 (6H, m), 6.45 (2H, td, J = 6.8, 1.1 Hz), 4.94 (2H, s), 3.88 (6H, s) ppm; δC (100
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MHz; CDCl3) = 159.8 (2xC), 145.0 (2xC), 144.1 (2xC), 130.27 (4xCH), 126.9 (2xC), 124.2
(2xCH), 123.9 (2xCH), 117.3 (2xCH), 114.4 (4xCH), 113.9 (2xC), 112.3 (2xCH), 55.5, 19.9
(CH2) ppm; HRMS (ESI): Calcd for C29H25N4O2 [M + H]+ 461.1978, Found: 461.1967.
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Bis(6ꢀbromoꢀ2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2i). Orange solid (202 mg,
66%); mp 286ꢀ288 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3683, 3019, 1602, 1522, 1475, 1023, 928, 669,
626; δH (400 MHz; CDCl3) = 7.75 (4H, br d, J = 7.7 Hz), 7.57 (4H, t, J = 7.2 Hz), 7.50ꢀ7.46 (2H,
m), 7.43ꢀ7.39 (4H, m), 7.11 (2H, dd, J = 9.4, 1.8 Hz), 4.92 (2H, s) ppm; δC (100 MHz; CDCl3) =
145.2 (2xC), 143.6 (2xC), 133.7 (2xC), 129.3 (4xCH), 129.2 (4xCH), 128.8 (2xCH), 128.0
(2xCH), 124.2 (2xCH), 118.1 (2xCH), 114.6 (2xC), 107.1 (2xC), 19.2 (CH2) ppm; HRMS (ESI):
Calcd for C27H18Br2N4 [M + H]+ 558.9956, Found: 558.9955.
Bis(6ꢀiodoꢀ2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2j). White solid (147 mg,
55%); mp 282ꢀ284 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3684, 3399, 3019, 1635, 1523, 1419, 1069, 928,
669; δH (400 MHz; CDCl3) = 7.81ꢀ7.79 (4H, m), 7.60ꢀ7.56 (6H, m), 7.48 (2H, t, J = 7.4 Hz),
7.31 (2H, d, J = 9.4 Hz), 7.22 (2H, dd, J = 9.4, 1.5 Hz), 4.93 (2H, s) ppm; δC (100 MHz; CDCl3 +
DMSOꢀd6 + TFA) = 138.8 (2xC), 138.4 (2xC), 135.7 (2xC), 129.5 (2xCH), 128.0 (10xCH),
126.7 (2xC), 115.3 (2xCH), 113.7 (2xCH), 79.8 (2xC), 19.1 (CH2) ppm; HRMS (ESI): Calcd for
C27H19I2N4 [M + H]+ 652.9699, Found: 652.9677.
Bis(6,8ꢀdichloroꢀ2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2k). White solid (206
mg, 67%); mp 268ꢀ270 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3390, 3019, 1637, 1402, 1068, 669; δH (400
MHz; CDCl3) = 7.77ꢀ7.75 (4H, m), 7.58ꢀ7.54 (4H, m), 7.51ꢀ7.47 (2H, m), 7.24 (2H, d, J = 1.7
Hz), 7.15 (2H, d, J = 1.7 Hz), 4.89 (2H, s) ppm; δC (100 MHz; CDCl3) = 146.0 (2xC), 141.1
(2xC), 133.2 (2xC), 129.3 (8xCH), 129.1 (2xCH), 124.9 (2xCH), 123.7 (2xC), 120.8 (2xCH),
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119.9 (2xC), 116.3 (2xC), 19.5 (CH2) ppm; HRMS (ESI): Calcd for C27H17Cl4N4 [M + H]+
537.0207, Found: 537.0200.
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Bis(2ꢀ(4ꢀbromophenyl)ꢀ6ꢀchloroimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2l). White solid
(199 mg, 65%); mp 273ꢀ275 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3683, 3390, 3019, 1645, 1522, 1403,
1069, 928, 831, 669, 626; δH (400 MHz; CDCl3) = 7.65ꢀ7.62 (4H, m), 7.57ꢀ7.54 (4H, m), 7.47
(2H, dd, J = 9.5, 0.1 Hz), 7.32 (2H, br d, J = 1.2 Hz), 7.07 (2H, dd, J = 9.5, 1.9 Hz), 4.80 (2H, s)
ppm; δC (100 MHz; CDCl3) = 144.4 (2xC), 143.5 (2xC), 132.6 (2xC), 132.3 (4xCH), 130.4
(4xCH), 126.3 (2xCH), 123.2 (2xC), 121.7 (2xCH), 121.0 (2xC), 118.0 (2xCH), 114.5 (2xC),
19.5 (CH2) ppm; HRMS (ESI): Calcd for C27H17Br2Cl2N4 [M + H]+ 626.9177, Found: 626.9145.
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Bis(7ꢀmethylꢀ2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2m). White solid (234 mg,
76%); mp 215ꢀ217 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3684, 3019, 1647, 1522, 1475, 1023, 928, 669;
δH (400 MHz; DMSOꢀd6) = 7.61 (2H, d, J = 6.9 Hz), 7.55 (4H, d, J = 6.9 Hz), 7.31ꢀ7.25 (8H, m),
6.57 (2H, d, J = 6.9 Hz), 4.97 (2H, s), 2.27 (6H, s) ppm; δC (100 MHz; CDCl3) = 145.5 (2xC),
143.8 (2xC), 135.3 (2xC), 134.7 (2xC), 129.0 (4xCH), 128.9 (4xCH), 128.1 (2xCH), 123.1
(2xCH), 115.8 (2xCH), 114.9 (2xCH), 114.0 (2xC), 21.24 (2xCH3), 19.8 (CH2) ppm; HRMS
(ESI): Calcd for C29H25N4 [M + H]+ 429.2079, Found: 429.2084.
Bis(6ꢀmethylꢀ2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2n). Yellow solid (246 mg,
80%); mp 273ꢀ275 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3673, 3391, 3019, 1637, 1402, 1216, 1068, 771,
669; δH (400 MHz; CDCl3) = 7.84 (4H, d, J = 7.1 Hz), 7.57 (4H, t, J = 7.4 Hz), 7.49ꢀ7.45 (2H,
m), 7.38 (2H, d, J = 9.2 Hz), 7.05 (2H, s), 6.86 (2H, dd, J = 9.1, 1.5 Hz), 4.96 (2H, s), 1.89 (6H,
s) ppm; δC (100 MHz; CDCl3) = 144.1 (2xC), 143.7 (2xC), 135.1 (2xC), 129.1 (8xCH), 128.3
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(2xCH), 127.6 (2xCH), 122.1 (2xCH), 121.8 (2xC), 116.6 (2xCH), 114.5 (2xC), 19.1 (CH2),
18.0 (2xCH3) ppm; HRMS (ESI): Calcd for C29H25N4 [M + H]+ 429.2079, Found: 429.2072.
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Bis(7ꢀethylꢀ2ꢀ(4ꢀmethoxyphenyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2o). White solid
(264 mg, 86%); mp 217ꢀ219 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3364, 1640, 1400, 1248, 1067, 837,
769; δH (400 MHz; CDCl3) = 7.74 (4H, dt, J = 9.6, 2.8 Hz), 7.27ꢀ7.24 (4H, m), 7.06 (4H, dt, J =
9.6, 2.8 Hz), 6.31 (2H, dd, J = 7.0, 1.7 Hz), 4.90 (2H, s), 3.89 (6H, s), 2.55 (4H, q, J = 7.5 Hz),
1.17 (6H, t, J = 7.5 Hz) ppm; δC (100 MHz; CDCl3) = 159.6 (2xC), 145.5 (2xC), 143.6 (2xC),
141.3 (2xC), 130.1 (4xCH), 127.1 (2xC), 123.3 (2xCH), 114.3 (4xCH), 114.2 (2xCH), 113.8
(2xCH), 113.5 (2xC), 55.4, 28.3 (2xCH2), 19.8 (CH2), 14.4 (2xCH3) ppm; HRMS (ESI): Calcd
for C33H33N4O2 [M + H]+ 517.2604, Found: 517.2592.
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Bis(2ꢀ(thiophenꢀ2ꢀyl)imidazo[1,2ꢀa]pyridineꢀ3ꢀyl)methane (2p). Offꢀwhite solid (185 mg,
60%); mp 259ꢀ261 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3392, 3019, 1636, 1403, 1215, 1051, 928, 669;
δH (400 MHz; CDCl3) = 7.59 (2H, d, J = 3.4 Hz), 7.53 (4H, br t, J = 8.0 Hz), 7.48 (2H, d, J = 4.8
Hz), 7.22ꢀ7.20 (2H, m), 7.09ꢀ7.05 (2H, m), 6.51 (2H, t, J = 6.3 Hz) 5.15 (2H, s) ppm; δC (100
MHz; CDCl3) = 145.3 (2xC), 138.6 (2xC), 137.0 (2xC), 128.0 (2xCH), 126.6 (2xCH), 125.9
(2xCH), 125.0 (2xCH), 123.9 (2xCH), 117.5 (2xCH), 113.6 (2xC), 112.9 (2xCH), 20.4 (CH2)
ppm; HRMS (ESI): Calcd for C23H17N4S2 [M + H]+ 413.0895, Found: 413.0887.
Bis(6ꢀphenylimidazo[2,1ꢀb]thiazolꢀ5ꢀyl)methane (2t). White solid (271 mg, 88%); mp
262ꢀ264 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3682, 3019, 1635, 1522, 1404, 1070, 928, 830, 669; δH
(500 MHz; CDCl3) = 7.75 (4H, br d, J = 7.7 Hz), 7.51ꢀ7.48 (4H, m), 7.41ꢀ7.37 (2H, m), 6.56
(2H, d, J = 3.6 Hz), 6.55 (2H, d, J = 3.6 Hz), 4.83 (2H, s) ppm; δC (100 MHz; CDCl3 + CD3OD)
= 149.4 (2xC), 144.4 (2xC), 133.9 (2xC), 128.9 (4xCH), 128.1 (4xCH), 128.0 (2xCH), 117.2
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(2xCH and 2xC, overlapped), 113.1 (2xCH), 21.0 (CH2) ppm; HRMS (ESI): Calcd for
C23H17N4S2 [M + H]+ 413.0895, Found: 413.0888.
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Bis(6ꢀ(4ꢀchlorophenyl)imidazo[2,1ꢀb]thiazolꢀ5ꢀyl)methane (2u). White solid (259 mg,
84%); mp 261ꢀ263 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3392, 3019, 1644, 1402, 1215, 1048, 928, 669;
δH (400 MHz; CDCl3) = 7.68ꢀ7.64 (4H, m), 7.46ꢀ7.43 (4H, m), 6.62 (2H, d, J = 4.5 Hz), 6.57
(2H, d, J = 4.5 Hz), 4.76 (2H, s) ppm; δC (100 MHz; CDCl3) = 149.6 (2xC), 143.7 (2xC), 133.8
(2xC), 132.8 (2xC), 129.2 (8xCH), 117.0 (2xCH), 113.4 (2xCH), 21.6 (CH2) ppm; HRMS (ESI):
Calcd for C23H15Cl2N4S2 [M + H]+ 481.0115, Found: 481.0110.
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Bis(6ꢀ(4ꢀfluorophenyl)imidazo[2,1ꢀb]thiazolꢀ5ꢀyl)methane (2v). White solid (256 mg,
83%); mp 253ꢀ255 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3390, 3019, 1645, 1403, 1215, 1156, 1068, 929,
669; δH (400 MHz; CDCl3) = 7.69 (4H, dd, J = 8.3, 5.4 Hz), 7.18 (4H, br t, J = 8.5 Hz), 6.61 (2H,
dd, J = 4.5, 0.6 Hz), 6.56 (2H, dd, J = 4.6, 0.6 Hz), 4.75 (2H, s) ppm; δC (100 MHz; CDCl3) =
162.5 (J = 246 Hz, 2xC), 149.4 (2xC), 143.9 (2xC), 130.4 (J = 3 Hz, 2xC), 129.7 (J = 8 Hz,
4xCH), 117.0 (2xCH), 116.8 (2xC), 115.9 (J = 22 Hz, 4xCH), 113.1 (2xCH), 21.4 (CH2) ppm;
HRMS (ESI): Calcd for C23H15F2N4S2 [M + H]+: 449.0706, Found: 449.0696.
Bis(6ꢀpꢀtolylimidazo[2,1ꢀb]thiazolꢀ5ꢀyl)methane (2w). White solid (277 mg, 90%); mp
254ꢀ256 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3369, 3019, 1637, 1403, 1215, 1069, 831, 769, 668; δH
(400 MHz; CDCl3) 7.64 (4H, d, J = 8.0 Hz), 7.30 (4H, d, J = 7.9 Hz), 6.56 (2H, d, J = 4.6 Hz),
6.54 (2H, d, J = 4.5 Hz), 4.80 (2H, s), 2.42 (6H, s) ppm; δC (100 MHz; CDCl3) 149.3 (2xC),
144.7 (2xC), 137.6 (2xC), 131.5 (2xC), 129.7 (4xCH), 127.9 (4xCH), 117.3 (2xCH), 117.0
(2xC), 112.6 (2xCH), 21.4 (CH2 and 2xCH3, overlapped) ppm; HRMS (ESI): Calcd for
C25H21N4S2 [M + H]+ 441.1208, Found: 441.1184.
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Bis(2ꢀphenylbenzo[d]imidazo[2,1ꢀb]thiazolꢀ3ꢀyl)methane (2x). White solid (191 mg,
65%); mp 277ꢀ279 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3684, 3019, 1604, 1497, 1404, 1215, 1025, 928,
669, 627; δH (400 MHz; CDCl3) = 7.68ꢀ7.64 (2H, m), 7.45ꢀ7.41 (2H, m), 7.32ꢀ7.28 (4H, m),
7.26ꢀ7.23 (4H, m), 7.18ꢀ7.12 (6H, m), 5.18 (2H, s) ppm; δC (100 MHz; CDCl3) = 147.3 (2xC),
145.9 (2xC), 133.6 (2xC), 133.2 (2xC), 130.6 (2xC), 128.1 (4xCH), 127.8 (4xCH), 127.6
(2xCH), 126.0 (2xCH), 124.5 (2xCH), 124.3 (2xCH), 118.9 (2xC), 113.0 (2xCH), 24.0 (CH2)
ppm; HRMS (ESI): Calcd for C31H21N4S2 [M + H]+ 513.1208, Found: 513.1195.
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Bis(2ꢀ(pꢀtolyl)phenylbenzo[d]imidazo[2,1ꢀb]thiazolꢀ3ꢀyl)methane (2y). White solid (208
mg, 68%); mp 314ꢀ316 ºC; FTꢀIR (KBr, νmax/cmꢀ1) 3683, 3392, 3019, 1645, 1522, 1403, 1069,
928, 831, 669, 626; δH (400 MHz; CDCl3) 7.66ꢀ7.64 (2H, m), 7.43ꢀ7.39 (2H, m), 7.30ꢀ7.25 (4H,
m), 7.12 (4H, d, J = 7.9 Hz), 6.93 (4H, d, J = 7.8 Hz), 5.13 (2H, s), 2.28 (6H, s) ppm; δC (100
MHz; CDCl3) 147.2 (2xC), 145.9 (2xC), 137.2 (2xC), 133.2 (2xC), 130.7 (2xC), 130.5 (2xC),
128.5 (4xCH), 128.0 (4xCH), 125.9 (2xCH), 124.4 (2xCH), 124.2 (2xCH), 118.8 (2xC), 113.0
(2xCH), 24.0 (CH2), 21.2 (2xCH3) ppm; HRMS (ESI): Calcd for C33H25N4S2 [M + H]+ 541.1521,
Found: 541.1506.
2ꢀ(4ꢀbromophenyl)ꢀ6ꢀchloroꢀ3ꢀ((2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀ
yl)methyl)Imidazo[1,2ꢀa]pyridine (3al). Orange solid (244 mg, 31%); mp 214ꢀ216 ºC; FTꢀIR
(KBr, νmax/cmꢀ1) 3683, 3019, 1602, 1522, 1476, 1070, 830, 669, 626; δH (400 MHz; CDCl3) =
7.72 (2H, d, J = 7.3 Hz), 7.65ꢀ7.60 (4H, m), 7.57ꢀ7.49 (3H, m), 7.45ꢀ7.40 (3H, m), 7.30 (1H, d, J
= 6.8 Hz), 7.11ꢀ7.08 (1H, m), 7.03 (1H, dd, J = 9.5, 1.8 Hz), 6.53 (1H, t, J = 6.8 Hz), 4.90 (2H, s)
ppm; δC (100 MHz; CDCl3) = 145.2 (C), 144.7 (C), 143.9 (C), 143.4 (C), 134.0 (C), 132.9 (C),
132.1 (2xCH), 130.3 (2xCH), 129.1 (2xCH), 129.0 (2xCH), 128.5 (CH), 126.1 (CH), 124.6
(CH), 123.5 (CH), 122.9 (C), 122.0 (CH), 120.8 (C), 117.8 (2xCH), 115.3 (C), 113.5 (C), 112.6
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(CH), 19.7 (CH2) ppm; HRMS (ESI): Calcd for C27H19BrClN4 [M + H]+ 513.0482, Found:
513.0476.
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phenylimidazo[1,2ꢀa]pyridine (3kh). White solid (192 mg, 29%); mp 174ꢀ176 ºC; FTꢀIR (KBr,
νmax/cmꢀ1) 3683, 3019, 1602, 1522, 1420, 1022, 928, 668, 626; δH (400 MHz; CDCl3) = 7.80
(2H, d, J = 7.1 Hz), 7.65 (2H, d, J = 8.6 Hz), 7.56ꢀ7.52 (3H, m), 7.47 (1H, br t, J = 7.2 Hz),
7.33 (1H, d, J = 1.6 Hz), 7.27 (1H, d, J = 6.9 Hz), 7.13 (1H, d, J = 1.6 Hz), 7.09ꢀ7.04 (3H, m),
6.49 (1H, t, J = 6.8 Hz), 4.90 (2H, s), 3.88 (3H, s) ppm; δC (100 MHz; CDCl3) = 160.0 (C),
145.6 (C), 145.1 (C), 144.5 (C), 141.0 (C), 133.6 (C), 130.3 (2xCH), 129.2 (2xCH), 129.1
(2xCH), 128.8 (CH), 126.4 (C), 124.6 (CH), 124.5 (CH), 123.6 (CH), 123.4 (C), 121.1 (CH),
119.6 (C), 117.6 (CH), 117.2 (C), 114.5 (2xCH), 113.1 (C), 112.4 (CH), 55.5, 19.7 (CH2) ppm;
HRMS (ESI): Calcd for C28H21Cl2N4O [M + H]+ 499.1092, Found: 499.1080.
6ꢀbromoꢀ3ꢀ((2ꢀ(4ꢀmethoxyphenyl)imidazo[1,2ꢀa]pyridinꢀ3ꢀyl)methyl)ꢀ2ꢀ
phenylimidazo[1,2ꢀa]pyridine (3hi). White solid (182 mg, 27%); mp 194ꢀ196 ºC; FTꢀIR (KBr,
νmax/cmꢀ1) 3683, 3389, 3019, 1634, 1522, 1403, 1069, 928, 831, 627; δH (400 MHz; CDCl3) =
7.78 (2H, d, J = 7.2 Hz), 7.69 (2H, d, J = 8.7 Hz), 7.56ꢀ7.44 (5H, m), 7.38 (1H, d, J = 9.5 Hz),
7.28 (1H, d, J = 6.9 Hz), 7.11ꢀ7.03 (4H, m), 6.45 (1H, td, J = 6.8, 0.9 Hz), 4.92 (2H, s), 3.88 (3H,
s) ppm; δC (100 MHz; CDCl3) = 159.9 (C), 145.0 (C), 144.9 (C), 144.4 (C), 143.4 (C), 134.1 (C),
130.4 (2xCH), 129.08 (2xCH), 129.0 (2xCH), 128.6 (CH), 127.8 (CH), 126.5 (C), 124.4 (CH),
124.3 (CH), 123.7 (CH), 118.0 (CH), 117.5 (CH), 115.3 (C), 114.6 (2xCH), 113.5 (C), 112.2
(CH), 107.0 (C), 55.5, 19.5 (CH2) ppm; HRMS (ESI): Calcd for C28H22BrN4O [M + H]+
509.0977, Found: 509.0977.
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yl)methyl)imidazo[2,1ꢀb]thiazole (3hu). Brown solid (219 mg, 35%); mp 234ꢀ236 ºC; FTꢀIR
(KBr, νmax/cmꢀ1) 3387, 3019, 1636, 1403, 1215, 1069, 929, 831, 668; δH (400 MHz; CDCl3) =
7.74 (2H, d, J = 8.7 Hz), 7.69 (2H, d, J = 8.4 Hz), 7.57 (1H, d, J = 9.0 Hz), 7.46 (2H, d, J = 8.4
Hz), 7.34 (1H, d, J = 6.9 Hz), 7.13ꢀ7.09 (1H, m), 7.04 (2H, d, J = 8.7 Hz), 6.56 (1H, td, J = 6.8,
0.7 Hz), 6.51 (1H, d, J = 4.6 Hz), 6.45 (1H, d, J = 4.6 Hz), 4.86 (2H, s), 3.88 (3H, s) ppm; δC
(100 MHz; CDCl3) = 159.8 (C), 149.5 (C), 145.0 (C), 143.9 (C), 143.7 (C), 133.7 (C), 133.0
(C), 129.9 (2xCH), 129.4 (2xCH), 129.1 (2xCH), 126.6 (C), 124.6 (CH), 123.3 (CH), 117.5
(CH), 117.4 (CH), 116.8 (C), 114.6 (2xCH), 114.0 (C), 112.9 (CH), 112.6 (CH), 55.5, 20.9
(CH2) ppm; HRMS (ESI): Calcd for C26H20ClN4OS [M + H]+ 471.1046, Found: 471.1076.
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2ꢀphenylimidazo[1,2ꢀa]pyridineꢀ3ꢀcarbaldehyde (4a).6a White solid (172 mg, 50%), mp
129ꢀ131 ºC (lit.,6a 128ꢀ130 ºC), FTꢀIR (KBr, νmax/cmꢀ1) 3401, 3019, 1630, 1328, 1211, 831, 758,
669; δH (400 MHz; CDCl3) 10.06 (1H, s), 9.66 (1H, dt, J = 6.8, 1.1 Hz), 7.84ꢀ7.79 (3H, m), 7.60ꢀ
7.50 (4H, m), 7.12 (1H, td, J = 6.9, 1.2 Hz); δC (100 MHz; CDCl3) 179.6, 158.4 (C), 147.8 (C),
132.4 (C), 130.5 (CH), 129.9 (3xCH), 128.98 (2xCH), 128.91 (CH), 120.8 (C), 117.5 (CH),
115.3 (CH); HRMS (ESI): Calcd for C14H11N2O [M + H]+ 223.0871, Found: 223.0870.
ASSOCIATED CONTENT
Supporting Information
1H and 13C NMR and HRMS spectra of all compounds. This material is available free of charge
via the internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
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*Eꢀmail: pp_yadav@cdri.res.in, ppy_cdri@yahoo.co.in
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Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGEMENTS
O. P. S. P. is thankful to UGC, New Delhi, and D. A. and R. K. M. are thankful to CSIR, New
Delhi, India for financial assistance. The authors are thankful Mr. Anoop K. Srivastava for
technical support and SAIFꢀCDRI, Lucknow, India for providing spectral and analytical data.
This work was supported by CSIR network project “HOPE” (BSC0114). This is CDRI
communication no. xxxx.
REFERENCES
(1) See reviews on DMSO as a synthon or reagent in organic chemistry: (a) JonesꢀMensah, E.;
Karki, M.; Magolan, J. Synthesis 2016, 48, 1421ꢀ1436. (b) Wu, X.ꢀF.; Natte, K. Adv. Syn. Catal.
2016, 358, 336ꢀ352.
(2) (a) Bagdi, A. K.; Santra, S.; Monir, K.; Hajra, A. Chem. Commun. 2015, 51, 1555ꢀ1575. (b)
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