One-Pot Tandem Amidation, Knoevenagel Condensation, and Palladium-Catalyzed Wacker Type Oxidation/C-O Coupling: Synthesis of Chromeno-Annulated Imidazopyridines

Article abstract of DOI:10.1021/acs.joc.8b00884

A direct one-pot synthesis of chromeno-annulated imidazo[1,2-a]pyridines is achieved by the reaction of 2-amino-1-(2-ethoxy-2-oxoethyl)pyridinium salts with 2-bromoarylaldehydes using Pd(TFA)₂ as a catalyst and Cu(OAc)₂ as an oxidant

Full text of DOI:10.1021/acs.joc.8b00884

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Article
One-Pot Tandem Amidation, Knoevenagel Condensation
and Palladium-Catalyzed Wacker Type Oxidation/C-O
Coupling: Synthesis of Chromeno-Annulated Imidazopyridines
Khima Pandey, Krishnan Rangan, and Anil Kumar
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00884 • Publication Date (Web): 08 Jun 2018
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OneꢀPot Tandem Amidation, Knoevenagel Condensation and
PalladiumꢀCatalyzed Wacker Type Oxidation/CꢀO Coupling:
Synthesis of ChromenoꢀAnnulated Imidazopyridines
Khima Pandey,a Krishnan Ranganb and Anil Kumar*,a
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aDepartment of Chemistry, BITS Pilani, Pilani Campus, Pilani 333031, India
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bDepartment of Chemistry, BITS Pilani, Hyderabad Campus, Secunderabad, Telangana, 500078,
India
E-mail: anilkumar@pilani.bits-pilani.ac.in
Abstract: A direct oneꢀpot synthesis of chromenoꢀannulated imidazo[1,2ꢀa]pyridines is achieved
by the reaction of 2ꢀaminoꢀ1ꢀ(2ꢀethoxyꢀ2ꢀoxoethyl)pyridinium salts with 2ꢀbromoarylaldehydes
using Pd(TFA)2 as catalyst and Cu(OAc)2 as an oxidant. The overall strategy involves tandem
baseꢀmediated amidation and Knoevenagel condensation, followed by palladiumꢀcatalyzed
Wacker type oxidation and intramolecular CꢀO coupling reaction. The method is simple,
tolerates different functional groups and gives moderate to good yields of
chromeno[2',3':4,5]imidazo[1,2ꢀa]pyridinꢀ12ꢀone derivatives. The developed tandem reaction
was also successfully applied for the synthesis of pyranoꢀfused imidazo[1,2ꢀa]pyridines by using
3ꢀbromoꢀ3ꢀarylacrylaldehydes.
Introduction
Imidazo[1,2ꢀa]pyridine is one of the most prominent class of Nꢀfused heterocycles which is
extensively found in diverse biologically active molecules and organometallics.1ꢀ3 Imidazo[1,2ꢀ
a]pyridine moiety is core structure of several drugs such as alpidem,4 zolpidem,5 olprinone,6 and
zolimidine7 (Figure 1) which are currently available in the market. Due to their wide range of
pharmaceutical, biological, and medicinal applications, imidazo[1,2ꢀa]pyridine heterocycles
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have drawn special attention of organic chemists.8 Similarly, chromones/chromanꢀ4ꢀones are
oxygenꢀcontaining heterocyclic scaffolds classified as privileged structures due to wide range of
biological activities displayed by the compounds based on these scaffolds.9ꢀ12 The annulated
aromatic systems containing two or more heterocycles are frequently encountered in numerous
natural and nonꢀnatural drug like products.9,13,14 The unique architecture of these molecules
benefits in their fundamental applications in pharmaceutical fields and development of organic
materials. In light of potential biological and functional properties associated with above
mentioned two moieties, it is reasonable to prospect that the hybrid of these two privileged
structures might be endowed with potent and unique biological activities. Thus synthesis of a
heterocyclic system incorporating these ‘privileged’ fragment is the subject of considerable
interest. For example, Proenca and Costa have synthesized chromenoꢀannulated imidazo[1,2ꢀ
a]pyridines by a domino oneꢀpot reaction of 2ꢀ(cyanomethyl)ꢀpyridinium chlorides and
salicylaldehydes in aqueous sodium carbonate solution.15,16 Voskressensky et al have
synthesized chromenoꢀannulated imidazoꢀpyrrolopyridines and imidazocarboline derivatives by
baseꢀpromoted domino reaction of oꢀhydroxy aryl aldehydes with azaindoleꢀ6ꢀcyanomethyl
chloride and N2ꢀ(cyanomethyl)ꢀβꢀcarbolinium bromide, respectively.17,18 They also achieved
imidazo[2,1ꢀa]isoquinolinesꢀfused chromene derivatives by the baseꢀcatalyzed reaction of Nꢀ
cyanomethylꢀisoquinolinium salts with oꢀhydroxy aryl aldehydes in a DMF/water mixture.19,20
Taran and Zou groups have independently prepared imidazo[1,2ꢀa]pyridines from 1ꢀ(2ꢀethoxyꢀ2ꢀ
oxoethyl)ꢀpyridinium salts.21,22 Although these methods proved successful and allowed facile
access to chromenoꢀannulated imidazoheterocycles, but they suffer from one or more limitations
such as narrow substrate scope, moderate yields and longer reaction time. Thus the development
of a new protocol for efficient access to chromenoꢀannulated imidazoheterocycles is highly
desirable.
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Figure 1: Selected drugs containing imidazo[1,2ꢀa]pyridine scaffold.
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On the other hand, domino processes also known as cascade or tandem reactions that involve
simultaneous formation of multiple new CꢀC/Cꢀheteroatom bond and generate high levels of
diversity and complexity under the same reaction conditions have become very attractive and
highly desirable in organic synthesis.23ꢀ25 These methods reduce generation of chemical waste
and reaction time. Transition metal catalyzed tandem reactions and in particular, palladiumꢀ
catalyzed domino transformations are an elegant approach to synthesize complex molecular
scaffolds.26
As part of our ongoing interest in developing synthetic methods for the preparation of fused
imidazo[1,2ꢀa]pyridines27ꢀ30 and on exploration of 2ꢀaminopyridinium salts in the synthesis of
fusedꢀheterocycles,31 we envisioned that a tandem reaction of 2ꢀaminoꢀ1ꢀ(2ꢀethoxyꢀ2ꢀ
oxoethyl)pyridinꢀ1ꢀium bromide with 2ꢀbromoarylaldehydes in the presence of a base and
palladium catalyst could give less explored chromeneꢀannulated imidazo[1,2ꢀa]pyridine
derivatives (Figure 2). Herein, we report our results for a oneꢀpot synthesis of chromenoꢀ
annulated imidazo[1,2ꢀa]pyridine via tandem amidation, Knoevenagel condensation, palladium
catalyzed Wacker type oxidation and CꢀO coupling reactions.
Figure 2. Schematic representation of the domino reactions for the synthesis of chromenoꢀ
annulated imidazo[1,2ꢀa]pyridine
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Results and discussion
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We initiated our study with a model reaction of 1a and 2a in the presence of Pd(OAc)2 (10 mol
%) and Cu(OAc)2 (2 equiv.) and K2CO3 (2.5 equiv.) in DMF at 120 °C for 10 h under air. To our
satisfaction, the 12Hꢀchromeno[2',3':4,5]imidazo[1,2ꢀa]pyridinꢀ12ꢀone (3aa) was obtained in
48% isolated yield (Table 1, entry 1). This encouraging result indicated the feasibility of the
envisioned tandem reaction. Thus, we went on to optimize the reaction conditions by varying
different catalysts, oxidants, bases, and solvents, etc. for the model reaction (Table 1). The
replacement of K2CO3 base with various other inorganic (KOH, Cs2CO3, tꢀBuOK) and organic
(DBU) bases demonstrated somewhat lower efficiency compared with K2CO3 (entries 2−5).
However, improved yield (61%) of 3aa was observed when the reaction was carried out with
K3PO4 (entry 6). We further examined the performance of the reaction with a series of palladium
catalysts such as PdCl2, Pd(TFA)2 and PdCl2(dppf)2 in the presence of Cu(OAc)2 and K3PO4
(entries 7ꢀ9) and to our satisfaction slightly better yield (67%) was obtained with Pd(TFA)2 as
compared to Pd(OAc)2. A sharp decrease in the yield of 3aa was observed when the reaction was
performed in the presence of other oxidants such as IBD, oxone, AgNO3, AgOAc and Ag(TFA)
(entries 10ꢀ14). In other polar solvents like DMA, DMF: H2O and PEGꢀ400 moderate yields of
3aa (48ꢀ69%) were obtained, whereas poor yield of 3aa was obtained in DMSO (entries 15ꢀ18),
Desired transformation did not occur in nonꢀpolar solvents such as toluene and dioxane (entry
19ꢀ20). It is also worth mentioning that the yield of 3aa decreased when the reaction was
performed under inert atmosphere (entry 21). Decreasing the loading of Cu(OAc)2 lead to
decrease in the yield of 3aa (entries 22ꢀ23). In the absence of Pd(TFA)2, no reaction was
observed (entry 24) while in the absence of Cu(OAc)2 only 10% of 3aa was formed (entry 25).
This observation showed that presence of both Cu(OAc)2 and Pd(TFA)2 is necessary for the
success of this reaction. Finally, the best yield of 3aa (77%) was obtained from the reaction of 1a
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(2 equiv.) with 2a (1 equiv.) in the presence of Pd(TFA)2 (10 mol %), Cu(OAc)2 (2.0 equiv.) in
DMF: H2O (1: 1 v/v) at 120 °C for 10 h under air (entry 26).
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Table 1: Optimization of the reaction condition.a
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Entry Pd catalyst
Oxidant
Base
K2CO3
KOH
Cs2CO3
DBU
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMA
% Yield of 3ab
1.
2.
3.
4.
5.
6.
7.
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
IBD
48
36
38
15
36
61
32
30
67
5
tꢀBuOK
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
8.
9.
PdCl2(dppf)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
ꢀ
10.
11.
12.
13.
14
15.
16.
17.
18.
19.
20
21.
22
23
24
25
Oxone
AgNO3
AgOAc
8
Trace
30
10
48
Ag(TFA)
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
ꢀ
DMF: H2Oc 69
PEGꢀ400
DMSO
Dioxane
Toluene
DMF
DMF
DMF
DMF
DMF
50
25
NR
Trace
52d
27e
50f
NR
10
Pd(TFA)2
DMF:
H2Oc
Pd(TFA)2
Cu(OAc)2
K3PO4
77g
26.
aReaction conditions: 1a (0.54 mmol), 2a (0.54 mmol) Pd catalyst (10 mol %), oxidant (2.0
b
c
equiv.), base (2.5 equiv.), solvent (8 mL), 120 °C, 10 h under open air; Isolated yields; DMF:
H2O (1: 1 v/v); dReaction performed under N2 atm; e1.0 equiv. of Cu(OAc)2 was used; f1.5 equiv.
g
of Cu(OAc)2 was used; 2.0 equiv. of 1a was used.
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With the optimized condition in hand, we embarked on investigation of the scope and limitation
of the methodology. As shown in table 2, different substituted 2ꢀaminopyridinium salts (1)
reacted smoothly with 2ꢀbromoarylaldehydes (2) to give corresponding chromenoꢀannulated
imidazo[1,2ꢀa]pyridines (3) in moderate to good yield (28ꢀ77%) under standardized conditions.
First scope of the tandem process was evaluated by using different 2ꢀbromoꢀarylaldehydes (2aꢀe)
having substituents such as methyl, fluoro, chloro, etc. No significant electronic influence was
observed on the yield of 3aa. Interestingly, heteroaromatic aldehydes 2ꢀbromopyridineꢀ3ꢀ
carbaldehyde (2f) and 2ꢀbromothiopheneꢀ3ꢀcarbaldehyde (2g) also reacted to furnish
corresponding chromenoꢀfused imidazo[1,2ꢀa]pyridines 3af and 3ag in 64% and 65% yields,
respectively. Finally, 1ꢀbromoꢀ3,4ꢀdihydronaphthaleneꢀ2ꢀcarbaldehyde (2h) was reacted with 2ꢀ
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aminopyridinium
salts
1a
to
give
corresponding
5,6ꢀdihydroꢀ7Hꢀ
benzo[7',8']chromeno[2',3':4,5]imidazo[1,2ꢀa]pyridinꢀ7ꢀones (3ah) in 35% yield. Next, scope of
2ꢀaminopyridinium salts was examined. It was found that the substituents on the pyridine ring of
2ꢀaminopyridinium salts significantly influenced the reaction outcome. For example, slightly
lower yields of the desired product were obtained from the Cꢀ5 substituted 2ꢀaminopyridinium
salts as compared to the unsubstituted or Cꢀ3ꢀsubstituted 2ꢀaminopyridinium salts. Along with
formation of the desired chromenoꢀannulated imidazo[1,2ꢀa]pyridines, cleavage of salts leading
to Nꢀacetylꢀ2ꢀaminopyridine derivatives (7d and 7e) was observed in case of the 5ꢀsubstituted 2ꢀ
aminopyridinium salts (3d and 3e). On the other hand, 5ꢀnitroꢀ2ꢀaminopyridinium salt failed to
give desired product under these conditions. Structures of all the synthesized compounds were
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elucidated by IR, H NMR, C NMR and HRMS data (See supporting information). The exact
structure of the product 3cd (CCDC 1585320) was unambiguously determined by single Xꢀray
diffraction analysis (Figure 3). The molecular structure of 3cd is planar in nature with all four
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fused rings including the substituted atoms such as chlorine, oxygen atom of the carbonyl group
and the carbon atom of the methyl group.
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Table 2: Substrate scope for synthesis of chromenoꢀannulated imidazo[1,2ꢀa]pyridines.a,b
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Pd(TFA)2 (10 mol %),
Cu(OAc)2 (2.0 equiv.)
N
O
Br
Br
O
R
R
N
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+
N
Ar
OEt
OHC
Ar
K3PO4, DMF:H2O (1:1)
120 °C, 10 h
NH2
O
2a-h
1a-e
3aa-ef
N
N
N
N
N
O
O
O
O
O
N
N
N
N
N
Me
OMe
OMe
O
O
O
O
O
F
Cl
3ac, 69%
3ae, 74%
3ab, 48%
3ad, 61%
3aa, 77%
N
N
N
N
O
N
N
O
O
O
N
O
N
N
N
Me
Me
S
N
Me
O
O
O
O
O
3bb, 31%
3ba, 64%
3ag, 65%
3ah, 35%
3af, 64%
N
N
N
N
N
N
O
O
O
O
N
N
Me
Me
N
Me
Me
OMe
OMe
O
O
O
O
Cl
Me
3be, 49%
3bf, 36%
F
3bd, 46%
3bc, 57%
Me
Me
Me
Me
N
N
N
N
N
O
N
O
O
O
O
N
N
N
N
OCH3
O
Me
O
O
O
O
OCH3
F
Cl
3ca, 62%
3cc, 65%
Me
3cb, 34%
3cd, 59%
3ce, 58%
Me
Me
N
O
N
N
N
O
N
O
O
N
N
Ph
N
N
N
S
O
O
O
O
3da, 48%
3ch, 37%
3cg, 63%
3cf, 68%
N
N
N
O
O
O
N
N
p-ClC6H4
N
p-ClC6H4
Me
Ph
O
O
O
3ef, 50%
3ea, 55%
3db, 28%
aReaction conditions: 1 (1.08 mmol), 2 (0.54 mmol), Pd(TFA)2 (18 mg, 0.054 mmol), Cu(OAc)2
(216 mg, 1.08 mmol), K3PO4 (286 mg, 1.351 mmol), DMF: H2O (8 mL, v/v), 120 °C, 10 h under
open air; bIsolated yields.
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Figure 3: ORTEP diagram of 3cd. The displacement ellipsoids are drawn at 50% probability level.
The compatibility of the method was further explored by reacting 2ꢀaminoꢀ1ꢀ(2ꢀethoxyꢀ2ꢀ
oxoethyl)pyridinium salts (1aꢀe) with 3ꢀbromoꢀ3ꢀarylacrylaldehydes (4aꢀb) and 3ꢀbromoꢀ3ꢀ(4ꢀ
bromophenyl)ꢀ2ꢀmethylacrylaldehyde (4c) (Table 3). The tandem reaction worked successfully
to give pyrano[2',3':4,5]imidazo[1,2ꢀa]pyridinꢀ4ꢀones (5aaꢀea) in moderate (29ꢀ57%) yields.
Table 3: Synthesis of pyrano[2',3':4,5]imidazo[1,2ꢀa]pyridinꢀ4ꢀones (5).a,b
O
N
OEt
Ar
O
O
N
N
Pd(TFA)2 (10 mol %), Cu(OAc)2 (2 equiv.)
Br
+
CHO
R
Br
NH2
K3PO4, DMF: H2O, 120 °C, 10 h
open vessel
Ar
R
1a-e
4a-c
5aa-ea
Cl
Br
Ph
O
O
Ph
O
N
N
N
O
O
O
N
N
N
N
N
O
H3C
CH3
O
5aa, 57%
5ba, 29%
5ac
5ab, 48%
, 40%
O
Cl
N
Ph
O
N
CH3
O
N
N
CH3
Ph
N
N
O
O
O
Cl
5ca, 45%
5cb, 42%
5ea
, 35%
aReaction conditions: 1 (1.08 mmol), 2 (0.54 mmol), Pd(TFA)2 (18 mg, 0.054 mmol), Cu(OAc)2
(216 mg, 1.08 mmol), K3PO4 (286 mg, 1.351 mmol), DMF: H2O (8 mL, v/v),120 °C, 10 h under
open air; bIsolated yields.
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Some controlled experiments were carried out in order to gain better understanding of the
mechanism and are presented in Scheme 1. Initially, reaction of 1a and 2a under standard
reaction conditions without the addition of palladium catalyst resulted in the formation of 3ꢀ(2ꢀ
bromobenzylidene)imidazo[1,2ꢀa]pyridinꢀ2(3H)ꢀone (6aa) in 65% yield (Scheme 1, a).
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Br-
N
N
Br
OEt
K3PO4, DMF
120 °C, 10 h
O
Br
N
+
a)
b)
O
OHC
NH2
6aa
, 65%
2a
1a
N
N
10 mol% Pd(TFA)2, Cu(OAc)2
O
O
N
N
K3PO4, DMF, 120 °C, 10 h
open vessel
O
6aa
Br
3aa,
72%
O
Br
OEt
N
Standard condition
N
c)
N
+
O
NH2
Br
9
2-
8
O
O
1a
N
O
N
N
Br
N
Br
OEt
Pd
O
N
O
O
O
O
Pd(TFA)2,
Cu(OAc)2
O
F3C
NH2
CF3
d)
B
+
N
N
K3PO4, DMF
120 °C, 5 h
O
O
+
Br
OH
OH
Br
N
N
N
N
OHC
O
Pd
O
2a
H3CCN
A
Pd
O
C
O
D
Observed in LC-HRMS
Observed in LC-HRMS
CF3
N
O
Br
Pd(TFA)2 (10 mol %),
Cu(OAc)2 (2.0 equiv.)
Br
OEt
O
N
N
e)
O
K3PO4, 120 °C, 10 h
OHC
NH2
1a
2a
3aa
DMF:H2O, Open vessel
= 77%
Dry DMF, MS 4Å, open vessel = 31%
Dry DMF, MS 4Å, N2 atm. = traces
CHO
Br
OEt
+
10 mol% Pd(TFA)2, Cu(OAc)2
N
N
f)
O
Other products
N
K3PO4, DMF, 120 °C, 10 h
open vessel
NH2
11, 10%
10
1a
Scheme 1 Controlled experiments
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Next, treatment of isolated 6aa with Pd(TFA)2 under the standard reaction conditions resulted in
the formation of 3aa in 72% yield (Scheme 1, b). This indicated that the reaction proceeds
through 6aa. Reaction of 1a and bromobenzene (8) under optimized reaction condition did not
occur to give 2ꢀphenoxyimidazo[1,2ꢀa]pyridine (9) which indicated that Oꢀarylation is not taking
place in the tandem reaction (Scheme 1, c). Further, aliquots of reaction between 1a and 2a
under standard reaction conditions at different time intervals were diluted with acetonitrile and
analyzed by LCꢀHRMS isocratic method using acetonitileꢀwater as eluent. Peaks corresponding
to the mass of intermediates A, B, C and D were observed at m/z 316.9921 (clcd for
C14H10BrN2O2 316.9926), 568.9393 (clcd for C18H9F6N2O6Pd 568.9400), 497.9824 (clcd for
C18H12F3N3O4Pd 497.9893) and 364.9524 (clcd for C14H8N2O2PdNa 364.9518), respectively in
HRMS spectrum (Scheme 1, d) indicating that the tandem reaction might be proceeding through
these intermediates. Finally, reaction of 1a and 2a under optimized reaction conditions using i)
anhydrous DMF in the presence of molecular sieves (MS 4Å) and ii) anhydrous DMF in the
presence of MS 4Å under nitrogen atmosphere led to drastic decrease in the yield of 3aa
(Scheme 1, e). This indicates that oxygen and H2O play very important role in the tandem
reaction. Reaction of 1a with benzaldehyde (10) resulted in the formation of 2ꢀ
phenylimidazo[1,2ꢀa]pyridine (11) in 10% yield along with other unidentified products (Scheme
1, f). Formation of 11 from 1a may be proceeding in a similar fashion as reported by Katritzky
group from 2ꢀaminoꢀ1ꢀ[αꢀbenzotriazolꢀ1ꢀylmethyl]pyridinium chlorides.32
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Although exact mechanism for the tandem reaction is unclear, based on the experimental results
and literature a plausible pathway for the formation of 3 or 5 from 1 is proposed in scheme 2.
Initially, base catalyzed intramolecular amidation of 2ꢀaminopyridinium salt 1 gives
imidazo[1,2ꢀa]pyridinꢀ2(3H)ꢀone (12) which on Knoevenagel condensation with 2ꢀ
bromoaldehyde (2 or 4) affords intermediate 6.33 The intermediate 6 then coordinates with Pd(II)
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to give I which then on reaction with water produces II via Wacker type oxidation.34ꢀ37
Intermediate II may lead to formation of palladacycle VII either through path A or path B. In
path B, palladium migrates to give intermediate VI which then results in the formation of VII
(observed in HRMS, Scheme 1, d). In path A, reductive elimination of II lead to formation of
III. Oxidative addition to Pd(0) leads to formation of intermediate IV which on exchange of
bromide with trifluroacetate leads to formation of V (observed in HRMS, Scheme 1, d).
Intermediate V converts to intermediate VII which on reductive elimination leads to the
formation of CꢀO bond and gives cyclized product 3 or 5.38
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Scheme 2. Proposed mechanism
CONCLUSION
In summary, we have developed a new synthetic methodology to access less explored chromeno
annulated imidazo[1,2ꢀa]pyridines through a oneꢀpot tandem reaction of 2ꢀaminoꢀ1ꢀ(2ꢀethoxyꢀ2ꢀ
oxoethyl)pyridinium salts with 2ꢀbromoarylaldehydes. The reaction involves tandem
intramolecular amidation, Knoevenagel condensation followed by palladiumꢀcatalyzed Wacker
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type oxidation and intramolecular CꢀO coupling reactions. Compared with previously reported
methods, this protocol is versatile, tolerates different functional groups and gives moderate to
good yields of chromeno[2',3':4,5]imidazo[1,2ꢀa]pyridinꢀ12ꢀone derivatives.
8
9
EXPERIMENTAL SECTION
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General. All reagents and solvents were purchased from commercial sources and used without
further purification. Melting points were measured using an automatic capillary point apparatus
and are uncorrected. The thin layer chromatography (TLC) was performed on 0.25 mm silica gel
60ꢀF254 and a UVꢀlamp was used as visualizing agent. Column chromatography was performed
1
using silica gel (100ꢀ200 mesh) and hexane and ethyl acetate were used as eluents. The H and
13C NMR spectra were obtained on 400 MHz and 100 MHz spectrometer. Coupling constant and
chemical shifts were reported in hertz (Hz) and parts per million (ppm) respectively, relative to
the internal standard of tetramethylsilane (TMS). IR spectroscopy was performed as a neat
sample on a FTꢀIR instrument and values are expressed in cmꢀ1. The HRMS were analyzed by
electrospray ionization (ESI) method in positive mode on a QꢀTOF LCꢀMS spectrometer.
Synthesis of βꢀbromoꢀα,βꢀunsaturated aldehydes (2h, 4aꢀc) was achieved from the reaction of
corresponding ketones and POBr3 following literature method.39
General Procedure for the Synthesis of 2ꢀAminopyridinium Bromides (1): An oven dried
round bottom (RB) flask was charged with 2ꢀaminopyridine (0.500 g, 5.31 mmol) and
tetrahydrofuran (15 mL). The RB flask was capped with rubber septum and after purging N2 gas,
ethyl bromoacetate (1.33 g, 7.96 mmol) was added via syringe and stirred the reaction mixture
under N2 gas atmosphere at 0 °C. The temperature of the reaction mixture was slowly raised to
room temperature and stirred for 8 h to obtain pink colored precipitate. After complete
consumption of 2ꢀaminopyridine as monitored by thin layer chromatography, reaction mixture
was filtered and residue was washed with diethyl ether to provide pure solid compound.
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2-Amino-1-(2-ethoxy-2-oxoethyl)pyridin-1-ium bromide 1a. Pink solid (1.3 g, 93%); mp.
4
5
1
Decomposed after 200 °C; H NMR (400 MHz, DMSOꢀd6) δ 8.74 (s, 1H), 8.08ꢀ8.07 (m, 1H),
6
7
8
9
7.99 – 7.75 (m, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.01 – 6.75 (m, 1H), 5.22 (s, 2H), 4.17 (q, J = 7.1
Hz, 2H), 1.22 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, DMSOꢀd6) δ 166.3, 155.1, 143.3, 140.8,
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115.4, 113.1, 62.4, 54.2, 14.4
.
FTꢀIR vmax (neat) 3286, 3062, 1739, 1651, 1577, 1338, 1126,
1099, 771 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C9H13N2O2 [MꢀBr]+ 181.0972, found
+
181.0970.
2-Amino-5-methyl-1-(2-ethoxy-2-oxoethyl)pyridin-1-ium bromide 1b. Pink solid (1.2 g, 96%);
1
mp. 280ꢀ282 °C; H NMR (400 MHz, DMSOꢀd6) δ 8.50 (s, 1H), 7.89 (s, 1H), 7.82 (d, J = 9.0
Hz, 1H), 7.09 (d, J = 9.1 Hz, 1H), 5.12 (s, 1H), 4.21 (q, J = 7.1 Hz, 2H), 2.15 (t, J = 7.1 Hz, 3H),
13
1.25 (t, J = 7.1 Hz, 3H); C NMR (100 MHz, DMSOꢀd6) δ 166.3, 153.7, 145.5, 138.2, 122.3,
115.2, 62.4, 54.0, 16.8, 14.4; FTꢀIR vmax (neat) 3329, 3290, 3124, 1743, 1658, 1523, 1373, 1211,
1022, 759 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C10H15N2O2 [MꢀBr]+ 195.1128, found
+
195.1135.
2-Amino-3-methyl-1-(2-ethoxy-2-oxoethyl)pyridin-1-ium bromide 1c. Pink solid (1.2 g, 96%);
1
mp. 296ꢀ298 °C; H NMR (400 MHz, DMSOꢀd6) δ 8.35 (s, 2H), 8.04 (d, J = 7.5 Hz, 1H), 7.86
(d, J = 7.2 Hz, 1H), 7.04 – 6.77 (m, 1H), 5.32 (s, 2H), 4.20 (q, J = 7.7 Hz, 2H), 2.26 (s, 3H), 1.25
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, DMSOꢀd6) δ 166.4, 154.2, 142.2, 138.9, 124.0, 112.8,
62.4, 54.8, 18.0, 14.4; FTꢀIR vmax (neat) 3286, 3070, 1743, 1666, 1585, 1342, 1219, 1022, 767
cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C10H15N2O2 [MꢀBr]+ 195.1128, found 195.1128.
+
2-Amino-1-(2-ethoxy-2-oxoethyl)-5-phenylpyridin-1-ium bromide 1d. Pink solid (0.90 g, 90%);
1
mp. 285ꢀ287 °C; H NMR (400 MHz, DMSOꢀd6) δ 8.79 (s, 2H), 8.53 (s, 1H), 8.36 (d, J = 8.9
Hz, 1H), 7.68 (d, J = 7.3 Hz, 2H), 7.52 (t, J = 7.2 Hz, 2H), 7.44 (d, J = 7.0 Hz, 1H), 7.25 (d, J =
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9.2 Hz, 1H), 5.25 (s, 1H), 4.23 (q, J= 6.7 Hz, 2H), 1.27 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz,
DMSOꢀd6) δ 166.3, 154.1, 142.0, 138.1, 134.2, 129.7, 128.9, 126.3, 125.3, 115.8, 62.5, 54.5,
14.4; ; FTꢀIR vmax (neat) 3271, 3244, 3074, 1751, 1662, 1346, 1288, 1095, 759 cmꢀ1; HRMS
8
9
+
(ESIꢀTOF, m/z): calcd for C15H17N2O2 [MꢀBr]+ 257.1287, found 257.1306.
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2-Amino-5-(4-chlorophenyl)-1-(2-ethoxy-2-oxoethyl)pyridin-1-ium bromide 1e. Off white solid,
(0.86 g, 95%); mp. 180ꢀ182 °C; 1H NMR (400 MHz, DMSOꢀd6) δ 8.83 (s, 2H), 8.57 (d, J = 1.6
Hz, 1H), 8.35 (dd, J = 9.3, 1.8 Hz, 1H), 7.71 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 8.6 Hz, 2H), 7.24
13
(d, J = 9.3 Hz, 1H), 5.23 (s, 2H), 4.23 (q, J = 7.1 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H); C NMR
(100 MHz, DMSOꢀd6) δ 166.2, 154.2, 141.7, 138.3, 133.7, 133.1, 129.7, 128.1, 125.2, 124.0,
115.8, 62.5, 54.5, 14.4; FTꢀIR vmax (neat) 3271, 3244, 3074, 1747, 1662, 1539, 1342, 1207, 1161,
1095, 813,752 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C15H16ClN2O2 [MꢀBr]+ 291.0895 found
+
291.0878.
2-Amino-1-(2-ethoxy-2-oxoethyl)-5-nitropyridin-1-ium bromide 1f. Off white solid, (0.25 g,
23%); mp. 135ꢀ138 °C; 1H NMR (400 MHz, DMSOꢀd6) δ 10.10 (bs, 1H), 9.42 (s, 1H), 8.55 (d, J
= 9.4 Hz, 1H), 7.27 (d, J = 9.8 Hz, 1H), 5.31 (s, 2H), 4.23 (q, J = 6.7 Hz, 2H), 1.27 (t, J = 6.9 Hz,
3H); 13C NMR (100 MHz, DMSOꢀd6) δ 165.8, 156.6, 141.8, 136.3, 135.4, 115.8, 62.6, 55.0,
14.4; FTꢀIR vmax (neat) 3325, 3147, 1762, 1658, 1543, 1361, 1215, 1168, 1053, 991,783 cmꢀ1;
+
HRMS (ESIꢀTOF, m/z): calcd for C9H12N3O4 [MꢀBr]+ 226.0822, found 226.0809.
General procedure for the synthesis of βꢀbromoꢀα,βꢀunsaturated aldehydes39: A dry round
bottom flask was charged with POBr3 (3 equiv.) in CHCl3 at 0 °C under N2 atmosphere. To this
cooled solution, N,Nꢀdimethylformamide (6 equiv.) was added drop wise over 10 min. and
stirred at room temperature for 45ꢀ60 min. Over the time, white precipitate was observed. To this
mixture, ketone (1 equiv.) dissolved in CHCl3 was added at 0 °C and then the resulting reaction
mixture was stirred for 10ꢀ15 h at 60 °C. After complete consumption of ketone as monitored by
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thin layer chromatography, reaction mass was poured in iceꢀcold water and the aqueous layer
was neutralized with solid K2CO3 and extracted with ethyl acetate. The combined organic layers
were washed with brine, dried over NaSO4, filtered, and concentrated in rotatory evaporator. The
crude product obtained was subjected to column chromatography using SiO2 and EA: hexane (5:
95 v/v) as eluting mixture to afford the βꢀbromoꢀα,βꢀunsaturated aldehydes.
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1-Bromo-3,4-dihydronaphthalene-2-carbaldehyde 2h. Yellow solid (0.580 g, 65%); H NMR
(400 MHz, CDCl3) δ 10.28 (s, 1H), 7.92 (dd, J = 7.2, 2.0 Hz, 1H), 7.43 – 7.31 (m, 2H), 7.22
13
(ddd, J = 5.9, 2.1, 1.0 Hz, 1H), 2.86 (dd, J = 9.2, 6.7 Hz, 2H), 2.71 – 2.53 (m, 2H); C NMR
(100 MHz, CDCl3) δ 193.14, 139.07, 138.95, 134.56, 133.03, 131.36, 128.75, 127.61, 127.15,
27.20, 22.91; FTꢀIR vmax (neat): 2864, 1682, 1570, 1500, 1220, 1149, 1040, 847, 712 cmꢀ1;
HRMS (APCIꢀTOF, m/z): calcd for C11H10BrO [M + H]+ 236.9910, 238.9890; found 236.9901,
238.9881.
1
3-Bromo-3-(4-bromophenyl)-2-methylacrylaldehyde 4c. Yellow liquid (0.550 g, 76%); H NMR
(400 MHz, CDCl3: 10:1 mixture of (E)/(Z)ꢀisomers) signals of (E)ꢀisomer: δ 9.42 (s, 1 H, CHO),
7.74–7.48 (m, 2 HAr), 7.38–7.04 (m, 2 HAr), 2.11 (s, 3 H, Me); additional signals of (Z)ꢀisomer:
δ = 10.21 (s, CHO), 1.80 (s, Me); 13C NMR (100 MHz, CDCl3; 10:1 mixture of (E)/(Z)ꢀisomers):
δ = 193.95 (Z), 188.34 (E), 146.12 (E), 139.84 (E), 138.23 (Z), 137.61 (Z), 136.54 (E), 135.05
(Z), 131.78 (Z), 131.72 (E), 131.44 (E), 129.99 (Z), 124.65 (E), 124. 10 (Z), 16.43 (E), 14.85
(Z); FTꢀIR vmax (neat): 2862, 1673, 1598, 1504, 1229, 1159, 1027, 906, 872, 835, 702 cmꢀ1;
HRMS (APCIꢀTOF, m/z): calcd for C10H9Br2O [M + H]+ 302.9015, 304.8994; found 302.8998,
304.8976.
Representative Procedure for the Synthesis of Chromeno/pyranoꢀAnnulated Imidazo[1,2ꢀ
a]pyridine (3 & 5). An ovenꢀdried 10 mL round bottom flask was charged with 2ꢀaminoꢀ1ꢀ(2ꢀ
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ethoxyꢀ2ꢀoxoethyl)pyridinꢀ1ꢀium bromide (0.282 g, 1.081 mmol), 2‒bromoaldehyde (0.100 g,
0.540 mmol), K3PO4 (0.286 g, 1.351 mmol), Cu(OAc)2 (0.216 g, 1.08 mmol), and Pd(TFA)2
(0.018 g, 0.054 mmol) in DMF: H2O (8 mL, v/v). The resulting reaction mixture was heated at
120 °C for 10 h. The reaction was monitored by TLC over the time. On completion, the reaction
mass was cooled to ambient temperature, diluted with ice cold water (20 mL), extracted with
ethyl acetate (2 × 30 mL). The combined organic layer was dried over anhydrous Na2SO4,
filtered and evaporated to dryness under reduced pressure. The crude residue was subjected to
column chromatography (30% EtOAc: hexane) to afford 3aa in 77% (98 mg) yield.
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12H-Chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3aa. Cream colored solid (0.098 g,
1
77%); MP 289 ‒ 291 °C; H NMR (400 MHz, CDCl3) δ 9.44 (d, J = 6.6 Hz, 1H), 8.43 (dd, J =
7.9, 1.1 Hz, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.78 – 7.73 (m, 1H), 7.70ꢀ7.67 (m, 2H), 7.50 (t, J =
7.3 Hz, 1H), 7.22 (t, J = 6.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 168.3, 161.3, 154.6, 145.3,
133.3, 131.0, 128.7, 125.9, 124.5, 123.8, 118.3, 116.8, 114.3, 107.6; FTꢀIR vmax (neat) 3093,
1643, 1604, 1442, 1249, 1111, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C14H9N2O2 [M + H]+
237.0659, found 237.0660.
3-Methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ab. Cream colored solid
(0.060 g, 48%); MP 266 ‒ 268 °C; 1H NMR (400 MHz, CDCl3) δ 9.49 – 9.41 (m, 1H), 8.31 (d, J
= 8.1 Hz, 1H), 7.81ꢀ 7.78 (m, 1H), 7.71 – 7.63 (m, 1H), 7.49 (s, 1H), 7.31 (dd, J = 8.1, 0.9 Hz,
13
1H), 7.21 (td, J = 6.9, 1.1 Hz, 1H), 2.57 (s, 3H); C NMR (100 MHz, CDCl3) δ 166.8, 161.3,
152.9, 145.5, 133.3, 131.4, 130.5, 128.8, 125.5, 125.0, 119.9, 116.9, 114.5, 107.5, 21.8; FTꢀIR
vmax (neat) 1643, 1612, 1442, 1381, 1249, 1111, 762 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for
C15H11N2O2 [M + H]+ 251.0815, found 251.0815.
2-Fluoro-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ac. Cream colored solid
1
(0.086 g, 69%); MP 234ꢀ236 °C; H NMR (400 MHz, CDCl3) δ 9.42 (dt, J = 6.7, 1.1 Hz, 1H),
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8.06 (dd, J = 8.4, 3.1 Hz, 1H), 7.80 (dt, J = 9.0, 1.0 Hz, 1H), 7.74 – 7.63 (m, 2H), 7.46 (ddd, J =
9.1, 7.4, 3.2 Hz, 1H), 7.24 (td, J = 6.9, 1.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.1 (d, J =
2.2 Hz), 161.4, 160.4, 158.0, 150.6, 145.5, 131.3, 128.8, 125.1 (d, J = 7.2 Hz), 121.0 (d, J = 25.1
Hz), 120.1 (d, J = 8.1 Hz), 115.7 (d, J = 242.7 Hz), 111.2 (d, J = 24.3 Hz), 107.3; FTꢀIR vmax
(neat) 3060, 1643, 1620, 1450, 1319, 1242, 1134, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for
C14H8FN2O2 [M + H]+ 255.0564, found 255.0566.
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2-Chloro-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ad. Cream colored solid
(0.075 g, 61%); MP 261 ‒ 263 °C; 1H NMR (400 MHz, CDCl3) δ 9.42 (d, J = 6.4 Hz, 1H), 8.38
(s, 1H), 7.81 (d, J = 8.9 Hz, 1H), 7.75 – 7.67 (m, 2H), 7.64 (d, J = 8.8 Hz, 1H), 7.25 (t, J = 6.7
13
Hz, 1H); C NMR (100 MHz, CDCl3) δ 166.8, 161.3, 152.9, 145.5, 133.3, 131.4, 130.5, 128.8,
125.5, 125.0, 119.9, 116.9, 114.5, 107.5; FTꢀIR vmax (neat) 2916, 1635, 1612, 1442, 1372, 1249,
1026, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C14H8ClN2O2 [M + H]+ 271.0269, found
271.0271.
2,3-Dimethoxy-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ae. Cream colored solid
(0.089 g, 74%); MP 280 ‒ 282 °C; 1H NMR (400 MHz, CDCl3) δ 9.43 (d, J = 6.6 Hz, 1H), 7.78
(d, J = 9.0 Hz, 1H), 7.76 (s, 1H), 7.69 – 7.62 (m, 1H), 7.21 (dd, J = 10.2, 3.5 Hz, 1H), 7.13 (s,
1H), 4.06 (s, 3H), 4.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.0, 161.0, 153.8, 150.3, 146.8,
144.8, 130.5, 128.6, 116.7, 116.5, 114.0, 105.0, 100.4, 56.5, 56.41; FTꢀIR vmax (neat) 2916, 1635,
1612, 1442, 1372, 1249, 1026, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C16H13N2O4 [M +
H]+ 297.0870, found 297.0866.
Pyrido[2",3":5,6]-5H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-5-one 3af. Yellow solid (0.081
g, 64%); MP >300 °C; 1H NMR (400 MHz, CDCl3) δ 9.40 (d, J = 6.6 Hz, 1H), 8.82 (dd, J = 7.7,
1.7 Hz, 1H), 8.78 (dd, J = 4.4, 1.7 Hz, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.73 (t, J = 7.7 Hz, 1H),
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7.56 (dd, J = 7.6, 4.7 Hz, 1H), 7.26 (d, J = 6.8 Hz, 1H); C NMR (100 MHz, CDCl3) δ 167.4,
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161.2, 159.0, 152.2, 145.9, 136.6, 131.5, 128.7, 121.3, 118.9, 117.2, 114.8, 107.6; FTꢀIR vmax
(neat) 3063, 1635, 1620, 1519, 1458, 1327, 1257, 1111, 1041, 763 cmꢀ1; HRMS (ESIꢀTOF, m/z):
calcd for C13H8N3O2 [M + H]+ 238.0611, found 238.0612.
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4H-Thieno[3'',2'':5',6']pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 3ag. Yellow solid (0.082 g,
1
65%); MP 202 ‒ 204 °C; H NMR (400 MHz, CDCl3 δ 9.40 (d, J = 6.6 Hz, 1H), 7.79 (dd, J =
6.8, 4.5 Hz, 2H), 7.66 (t, J = 7.9 Hz, 1H), 7.34 (d, J = 5.4 Hz, 1H), 7.21 (t, J = 6.7 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 165.4, 161.6, 156.0, 144.7, 131.3, 130.5, 128.5, 123.8, 118.1, 116.9,
114.2, 107.8; FTꢀIR vmax (neat) 3074, 2954, 2920, 1624, 1512, 1458, 1307, 1249, 1145, 1029,
763 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C12H7N2O2S [M + H]+ 243.0223, found 243.0228.
5,6-Dihydro-7H-benzo[7',8']chromeno[2',3':4,5]imidazo[1,2-a]pyridin-7-one 3ah. Yellow solid
(0.042, 35%); 1H NMR (400 MHz, CDCl3) δ 9.37 (dt, J = 6.7, 1.3 Hz, 1H), 8.08 (dd, J = 5.6, 3.5
Hz, 1H), 7.77 (dt, J = 9.1, 1.2 Hz, 1H), 7.63 (ddd, J = 8.9, 7.0, 1.4 Hz, 1H), 7.42 (dd, J = 5.6, 3.3
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Hz, 2H), 7.32 (dd, J = 5.4, 3.4 Hz, 1H), 7.17 (td, J = 6.9, 1.2 Hz, 1H), 3.03ꢀ3.00 (m, 4H); C
NMR (100 MHz, CDCl3) δ 169.7, 160.3, 155.2, 144.4, 138.6, 130.6, 130.2, 128.4, 128.4, 128.0,
127.1, 123.9, 118.8, 116.8, 113.8, 27.2, 18.9; FTꢀIR vmax (neat): 3093, 2935, 1647, 1600, 1450,
1258, 1100, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C18H13N2O2 [M + H]+ 289.0972 found
289.0979.
9-Methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ba. Cream colored solid
(0.086 g, 64%); MP 215 ‒ 217 °C; 1H NMR (400 MHz, CDCl3) δ 9.26 (d, J = 0.8 Hz, 1H), 8.43
(dd, J = 7.9, 1.5 Hz, 1H), 7.75 (ddd, J = 8.6, 7.1, 1.7 Hz, 1H), 7.71 – 7.66 (m, 2H), 7.53 (dd, J =
9.2, 1.7 Hz, 1H), 7.52 – 7.47 (m, 1H), 2.51 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.2, 161.2,
154.6, 144.1, 133.8, 133.2, 126.8, 125.9, 124.4, 124.4, 123.8, 118.3, 116.1, 107.4, 18.2; FTꢀIR
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vmax (neat) 3093, 3039, 2916, 1643, 1519, 1458, 1317, 1248, 1188, 756 cmꢀ1; HRMS (ESIꢀTOF,
m/z): calcd for C15H11N2O2 [M + H]+ 251.0815, found 251.0813.
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3,9-Dimethyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3bb.: Off white solid
(0.041 g, 31%); MP 207 ‒ 209 °C; 1H NMR (400 MHz, CDCl3) δ 9.24 (d, J = 0.8 Hz, 1H), 8.29
(d, J = 8.1 Hz, 1H), 7.68 (d, J = 9.1 Hz, 1H), 7.50 (dd, J = 9.1, 1.6 Hz, 1H), 7.46 (s, 1H), 7.30 ꢀ
7.28 (m, 1H), 2.55 (s, 3H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8, 161.2, 152.8,
144.3, 134.2, 133.2, 130.3, 126.8, 125.5, 125.0, 124.8, 119.8, 116.2, 107.4, 18.2; FTꢀIR vmax
(neat) 3032, 2929, 2854, 1620, 1519, 1465, 1303, 1234, 1118, 1041, 817, 763 cmꢀ1; HRMS (ESIꢀ
TOF, m/z): calcd for C16H13N2O2 [M + H]+ 265.0972, found 265.0980.
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2-Fluoro-9-methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3bc. Cream colored
solid (0.075 g, 57%); MP 230 ‒ 232 °C; 1H NMR (400 MHz, CDCl3) δ 9.33 – 9.17 (m, 1H), 8.07
(dd, J = 8.4, 3.1 Hz, 1H), 7.71 (d, J = 9.5 Hz, 1H), 7.69 – 7.65 (m, 1H), 7.56 (dd, J = 9.1, 1.7 Hz,
13
1H), 7.46 (ddd, J = 9.1, 7.4, 3.2 Hz, 1H), 2.51 (s, 3H); C NMR (100 MHz, CDCl3) δ 167.1,
161.4, δ 159.2 (d, J = 245.5 Hz), 157.8, 150.6, 144.3, 134.2, 126.8, 125.2 (d, J = 7.2 Hz), 124.7,
120.9 (d, J = 25.1 Hz), 120.0 (d, J = 8.1 Hz), 116.2, 111.2 (d, J = 24.3 Hz), 107.2, 18.2; FTꢀIR
v
max (neat) 3063, 1635, 1519, 1465, 1303, 1234, 1118, 1041, 817, 763 cmꢀ1; HRMS (ESIꢀTOF,
m/z): calcd for C15H10FN2O2 [M + H]+ 269.0721, found 269.0722.
2-Chloro-9-methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3bd. Off white solid
1
(0.060 g, 46%); MP 248 ‒ 249 °C; H NMR (400 MHz, CDCl3) δ 9.24 (s, 1H), 8.38 (d, J = 2.5
Hz, 1H), 7.71 (d, J = 8.9 Hz, 1H), 7.69ꢀ7ꢀ67 (m, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.56 (dd, J = 9.1,
1.6 Hz, 1H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8, 161.2, 152.8, 144.3, 134.2,
133.2, 130.3, 126.8, 125.5, 125.0, 124.8, 119.8, 116.2, 107.4, 18.2; FTꢀIR vmax (neat) 3063, 1635,
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1519, 1465, 1303, 1234, 1118, 1041, 817, 763 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for
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C15H10ClN2O2 [M + H]+ 285.0425, found 285.0422.
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2,3-Dimethoxy-9-methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3be. Yellow
9
1
viscous liquid (0.062 g, 49%); H NMR (400 MHz, CDCl3) δ 9.24 (s, 1H), 7.76 (s, 1H), 7.68 (d,
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J = 9.1 Hz, 1H), 7.50 (dd, J = 9.1, 1.5 Hz, 1H), 7.12 (s, 1H), 4.06 (s, 6H), 2.51 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.9, 160.9, 153.7, 150.3, 146.7, 143.6, 133.4, 126.6, 124.1, 116.6, 116.0,
107.1, 105.1, 100.4, 56.5, 56.4, 18.2; FTꢀIR vmax (neat) 2958, 2924, 1631, 1612, 1504, 1462,
1427, 1261, 1222, 1111, 1020, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C17H15N2O4 [M +
H]+ 311.1026, found 311.1031.
8-Methyl-pyrido[2",3":5',6']-5H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-5-one 3bf. White
solid (0.048 g, 36%); MP 271 ‒ 273 °C; 1H NMR (400 MHz, CDCl3) δ 9.21 (s, 1H), 8.82 (dd, J
= 7.7, 2.0 Hz, 1H), 8.77 (dd, J = 4.6, 2.0 Hz, 1H), 7.75 (d, J = 9.1 Hz, 1H), 7.60 – 7.56 (m, 1H),
7.56 – 7.52 (m, 1H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 161.1, 159.0, 152.1,
144.7, 136.7, 134.45, 126.7, 125.0, 121.2, 118.9, 116.5, 107.4, 18.2; FTꢀIR vmax (neat) 3085,
2927, 1637, 1519, 1458, 1340, 1240, 1020, 757 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for
C14H10N3O2 [M + H]+ 252.0768, found 252.0770.
7-Methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ca. Cream colored solid
(0.083 g, 62%); MP 253 ‒ 254 °C; 1H NMR (400 MHz, CDCl3) δ 9.31 (d, J = 6.5 Hz, 1H), 8.44
(d, J = 7.9 Hz, 1H), 7.80 – 7.72 (m, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.14
(t, J = 6.9 Hz, 1H), 2.72 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.3, 154.6, 133.2, 130.1,
126.9, 126.42, 125.9, 124.5, 123.9, 118.3, 114.3, 107.9, 16.8; FTꢀIR vmax (neat) 3063, 2916,
1643, 1512, 1450, 1381, 1257, 1056, 779 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C15H11N2O2
[M + H]+ 251.0815, found 251.0816.
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3,7-Dimethyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3cb. Cream colored solid
(0.045 g, 34%); MP 256 ‒ 258 °C; 1H NMR (400 MHz, CDCl3) δ 9.30 (d, J = 6.6 Hz, 1H), 8.30
(d, J = 8.1 Hz, 1H), 7.52 – 7.47 (m, 1H), 7.46 (s, 1H), 7.31 (d, J = 9.1 Hz, 1H), 7.12 (t, J = 6.9
13
Hz, 1H), 2.72 (s, 1H), 2.56 (s, 3H); C NMR (100 MHz, CDCl3) δ 168.4, 160.9, 154.7, 145.2,
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144.6, 129.9, 126.8, 126.3, 125.8, 125.7, 121.5, 118.2, 114.2, 107.8, 21.8, 16.8; FTꢀIR vmax (neat)
3117, 2916, 1651, 1620, 1519, 1450, 1381, 1272, 1111, 771 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd
for C16H13N2O2 [M + H]+ 265.0972, found 265.0980.
2-Fluoro-7-methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3cc. Cream colored
solid (0.085 g, 65%); MP 227 ‒ 228 °C; 1H NMR (400 MHz, CDCl3) δ 9.28 (d, J = 6.5 Hz, 1H),
8.07 (dd, J = 8.3, 3.0 Hz, 1H), 7.67 (dd, J = 9.1, 4.1 Hz, 1H), 7.51 (d, J = 7.2 Hz, 1H), 7.49 –
7.41 (m, 1H), 7.15 (t, J = 6.9 Hz, 1H), 2.72 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.2, 161.1,
160.4, 158.0, 150.6, 145.6, 130.5, 127.0, 126.4, 125.1, δ 120.9 (d, J = 25.1 Hz), 120.0 (d, J = 8.1
Hz), 114.5, 111.2 (d, J = 24.3 Hz), 16.8; FTꢀIR vmax (neat) 3063, 1658, 1612, 1450, 1373, 1257,
1056, 779 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C15H10FN2O2 [M + H]+ 269.0721, found
269.0722.
2-Chloro-7-methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3cd. Cream colored
solid (0.076 g, 59%); MP 273 ‒ 275 °C; 1H NMR (400 MHz, CDCl3) δ 9.27 (d, J = 6.6 Hz, 1H),
8.37 (d, J = 2.5 Hz, 1H), 7.68 (dd, J = 8.9, 2.6 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 7.2
Hz, 1H), 7.15 (t, J = 6.9 Hz, 1H), 2.71 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8, 160.9,
152.9, 145.6, 133.2, 130.51, 130.4, 127.1, 126.4, 125.4, 125.0, 119.8, 114.6, 107.8, 16.8; FTꢀIR
v
max (neat) 3063, 1658, 1612, 1450, 1373, 1257, 1056, 779 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd
for C15H10ClN2O2 [M + H]+ 285.0425, found 285.0430.
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2,3-Dimethoxy-7-methyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ce. Cream
colored solid (0.073 g, 58%); MP 250 ‒ 252 °C; 1H NMR (400 MHz, CDCl3) δ 9.30 (d, J = 6.6
Hz, 1H), 7.77 (s, 1H), 7.46 (d, J = 7.1 Hz, 1H), 7.13 (d, J = 6.9 Hz, 1H), 7.10 (s, 1H), 4.06 (s,
3H), 4.05 (s, 3H), 2.72 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.1, 160.7, 153.7, 150.3, 147.2,
146.8, 131.1, 129.6, 126.8, 126.3, 116.6, 114.1, 105.1, 100.4, 56.5, 56.4, 16.9; FTꢀIR vmax (neat)
2924, 2850, 1666, 1635, 1612, 1504, 1458, 1438, 1257, 1226, 1114, 1026, 740 cmꢀ1; HRMS
(ESIꢀTOF, m/z): calcd for C17H15N2O4 [M + H]+ 311.1026, found 311.1028.
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10-Methyl-pyrido[2",3":5',6']-5H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-5-one 3cf. White
solid (0.091 g, 68%); MP 238 ‒ 239 °C; 1H NMR (400 MHz, CDCl3) δ 9.26 (d, J = 6.5 Hz, 1H),
8.82 (dd, J = 7.7, 1.9 Hz, 1H), 8.78 (dd, J = 4.6, 1.9 Hz, 1H), 7.58 – 7.54 (m, 1H), 7.54 – 7.50
13
(m, 1H), 7.17 (t, J = 6.9 Hz, 1H), 2.74 (s, 3H); C NMR (100 MHz, CDCl3) δ 167.4, 160.9,
159.0, 152.1, 145.9, 136.6, 130.7, 127.4, 126.3, 121.2, 119.0, 114.8, 107.9, 16.9; FTꢀIR vmax
(neat) 3085, 1640, 1609, 1519, 1458, 1357, 1240, 1109, 1041, 757 cmꢀ1; HRMS (+ESIꢀTOF,
m/z): calcd for C14H10N3O2 [M + H]+ 252.0768, found 252.0767
9-Methyl-4H-thieno[3'',2'':5',6']pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 3cg. Yellow solid
1
(0.084 g, 63%); MP 248 ‒ 250 °C; H NMR (400 MHz, CDCl3δ 9.25 (d, J = 6.6 Hz, 1H), 7.76
(d, J = 5.4 Hz, 1H), 7.45 (d, J = 7.1 Hz, 1H), 7.32 (d, J = 5.4 Hz, 1H), 7.11 (t, J = 6.9 Hz, 1H),
2.70 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.4, 161.2, 156.0, 144.81, 131.15, 129.52,
127.00, 126.20, 123.81, 118.11, 114.22, 108.16, 16.88; FTꢀIR vmax (neat) 3097, 2954, 2920,
1654, 1620, 1512, 1450, 1381, 1253, 1161, 1053, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for
C13H9N2O2S [M + H]+ 257.0379, found 257.0381.
12-Methyl-5,6-dihydro-7H-benzo[7',8']chromeno[2',3':4,5]imidazo[1,2-a]pyridin-7-one
3ch.
Red solid (0.047, 37%); 1H NMR (400 MHz, CDCl3) δ 9.22 (d, J = 6.7 Hz, 1H), 8.15 – 8.01 (m,
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1H), 7.53 – 7.36 (m, 2H), 7.35 – 7.27 (m, 1H), 7.08 (t, J = 6.9 Hz, 1H), 3.03ꢀ2.99 (m, 4H), 2.72
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(s, 3H); C NMR (100 MHz, CDCl3) δ 169.8, 159.9, 155.1, 144.5, 138.6, 130.5, 129.3, 128.5,
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9
127.9, 127.1, 126.8, 126.1, 123.9, 118.7, 113.9, 27.2, 18.9, 16.9; FTꢀIR vmax (neat): 3093, 2854,
1650, 1604, 1420, 1250, 1149, 1040, 847, 712, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for
C19H15N2O2 [M + H]+ 303.1128 found 303.1148.
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9-Phenyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3da. Off white solid (0.080 g,
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48%); MP 248 ‒ 250 °C; H NMR (400 MHz, CDCl3) δ 9.67 (s, 1H), 8.45 (d, J = 7.9 Hz, 1H),
7.95 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 9.2 Hz, 1H), 7.78 (t, J = 7.0 Hz, 1H), 7.74 – 7.65 (m, 3H),
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7.57 (s, 1H), 7.56 – 7.51 (m, 2H), 7.50 – 7.45 (m, 1H); C NMR (100 MHz, CDCl3) δ 168.3,
161.5, 154.6, 144.5, 136.1, 133.3, 131.2, 129.3, 129.0, 128.5, 127.1, 126.0, 125.9, 124.5, 123.8,
118.3, 116.6, 107.8; FTꢀIR vmax (neat) 3063, 1635, 1519, 1458, 1327, 1257, 1080, 1018, 802, 756
cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C20H13N2O2 [M + H]+ 313.0972, found 313.0974.
3-Methyl-9-phenyl-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3db. Off white solid
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(0.045 g, 28%); MP 260 ‒ 262 °C; H NMR (400 MHz, CDCl3) δ 9.66 (s, 1H), 8.31 (d, J = 8.1
Hz, 1H), 7.93 (dd, J = 9.3, 1.8 Hz, 1H), 7.85 (d, J = 9.2 Hz, 1H), 7.69 (d, J = 7.3 Hz, 2H), 7.55
(t, J = 7.5 Hz, 2H), 7.50 (s, 1H), 7.50 – 7.45 (m, 1H), 7.32 (d, J = 7.9 Hz, 1H), 2.58 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 168.4, 161.4, 154.8, 144.7, 144.3, 136.1, 131.0, 129.3, 128.9, 128.4,
127.1, 125.9, 125.9, 125.7, 121.5, 118.3, 116.6, 107.7, 21.8; FTꢀIR vmax (neat) 3063, 1635, 1620,
1519, 1458, 1327, 1257, 1111, 1041, 763 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C21H15N2O2
[M + H]+ 327.1128, found 327.1137.
9-(4-Chlorophenyl)-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-12-one 3ea. Off white solid
(0.102 g, 55%); MP 261 ‒ 263 °C; 1H NMR (400 MHz, CDCl3) δ 9.64 (s, 2H), 8.44 (dd, J = 7.9,
1.5 Hz, 1H), 7.93 – 7.83 (m, 2H), 7.82 – 7.75 (m, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.66 – 7.59 (m,
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2H), 7.55 – 7.52 (m, 2H), 7.52 – 7.49 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 168.4, 161.5,
154.6, 144.4, 134.8, 134.6, 133.5, 130.8, 129.5, 128.4, 127.8, 126.00, 125.8, 124.6, 123.8, 118.4,
116.8, 107.9; FTꢀIR vmax (neat) 3097, 3062, 1666, 1635, 1519, 1465, 1334, 1257, 1095, 1010,
810, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C20H12ClN2O2 [M + H]+ 347.0582, found
347.0594.
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8-(4-Chlorophenyl)-pyrido[2",3":5',6']-5H-chromeno[2',3':4,5]imidazo[1,2-a]pyridin-5-one 3ef.
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Sticky white compound (0.093 g, 50%); H NMR (400 MHz, CDCl3) δ 9.57 (s, 1H), 8.83 (dd, J
= 7.7, 2.0 Hz, 1H), 8.80 (dd, J = 4.6, 2.0 Hz, 1H), 7.95ꢀ7.89 (m, 2H), 7.65 – 7.60 (m, 2H), 7.58
(dd, J = 7.7, 4.7 Hz, 1H), 7.55 – 7.51 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 167.5, 161.4,
159.0, 152.3, 145.0, 136.7, 134.9, 134.3, 131.4, 129.6, 128.4, 128.3, 125.8, 121.4, 118.9, 117.2,
107.8; FTꢀIR vmax (neat) 2948, 1640, 1519, 1460, 1320, 1223, 1020, 815, 757 cmꢀ1; HRMS (ESIꢀ
TOF, m/z): calcd for C19H11ClN3O2 [M + H]+ 348.0534, found 348.0531.
2-Phenyl-4H-pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 5aa. Brown viscous liquid (0.070 g,
57%); 1H NMR (400 MHz, CDCl3) δ 9.31 (d, J = 6.0 Hz, 1H), 8.05 – 7.89 (m, 2H), 7.78 (d, J =
8.7 Hz, 1H), 7.70 – 7.60 (m, 1H), 7.59 – 7.49 (m, 3H), 7.18 (t, J = 6.2 Hz, 1H), 6.90 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 170.3, 161.1, 160.8, 150.4, 144.5, 131.4, 131.2, 130.5, 129.1, 128.5,
126.3, 116.9, 114.1, 109.7; FTꢀIR vmax (neat) 3063, 1653, 1600, 1439, 1249, 1109, 756 cmꢀ1;
HRMS (ESIꢀTOF, m/z): calcd for C16H11N2O2 [M + H]+ 263.0815, found 263.0822.
2-(4-Chlorophenyl)-4H-pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 5ab. Viscous liquid
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(0.058 g, 48%); H NMR (400 MHz, CDCl3) δ 9.31 (d, J = 6.7 Hz, 1H), 7.96 – 7.87 (m, 2H),
7.79 (d, J = 9.1 Hz, 1H), 7.71 – 7.61 (m, 1H), 7.57 – 7.50 (m, 2H), 7.20 (td, J = 6.9, 1.0 Hz, 1H),
6.88 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 170.1, 161.0, 159.7, 144.6, 137.5, 131.4, 130.7,
129.9, 129.4, 128.5, 127.5, 116.9, 114.2, 109.8; FTꢀIR vmax (neat) 3020, 2920, 2850, 1643, 1627,
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1524, 1450, 1257, 1114, 1091, 1006, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C16H10ClN2O2
[M + H]+ 297.0425, 299. 0401 found 297.0427 and 299.0399.
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solid (0.054, 40%); H NMR (400 MHz, CDCl3) δ 9.36 (d, J = 6.7 Hz, 1H), 7.77 (d, J = 9.1 Hz,
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1H), 7.69 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.57 (d, J = 8.2 Hz, 2H), 7.18 (t, J = 6.9
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Hz, 1H), 2.24 (s, 3H); C NMR (100 MHz, CDCl3) δ 170.6, 160.6, 156.6, 153.9, 131.9, 131.7,
130.8, 130.5, 130.5, 128.4, 124.6, 119.6, 116.8, 113.9, 11.7; FTꢀIR vmax (neat): 3035, 2839, 1656,
1600, 1389, 1250, 1111, 756, 715 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for C17H12BrN2O2 [M +
H]+ 355.0077, found 355.0065 and 357.0044.
7-Methyl-2-phenyl-4H-pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 5ba. Cream solid (0.038 g,
29%); MP 284 ‒ 286 °C; 1H NMR (400 MHz, CDCl3) δ 9.12 (s, 1H), 8.06 – 7.90 (m, 2H), 7.67
(d, J = 9.1 Hz, 1H), 7.59 – 7.52 (m, 3H), 7.49 (d, J = 9.1 Hz, 1H), 6.89 (s, 1H), 2.48 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 170.3, 161.0, 160.6, 143.4, 133.5, 131.5, 131.1, 129.0, 126.5, 126.2,
124.2, 116.2, 109.6, 18.1; FTꢀIR vmax (neat) 3093, 1650, 1604, 1420, 1256, 1111, 756 cmꢀ1;
HRMS (ESIꢀTOF, m/z): calcd for C17H13N2O2 [M + H]+ 277.0972, found 277.0969.
9-Methyl-2-phenyl-4H-pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 5ca. Cream solid (0.059 g,
45%); δ 9.18 (d, J = 6.5 Hz, 1H), 8.00 (d, J = 3.5 Hz, 2H), 7.58 – 7.49 (m, 3H), 7.46 (d, J = 7.0
Hz, 1H), 7.10 (t, J = 6.9 Hz, 1H), 6.91 (s, 1H), 2.72 (s, 3H); 13C NMR (100 MHz, CDCl3δ 170.4,
160.7, 151.3, 144.7, 131.5, 131.2, 129.6, 129.0, 126.9, 126.3, 126.2, 114.1, 109.7, 16.9; FTꢀIR
vmax (neat) 3097, 2924, 2854, 1627, 1573, 1446, 1253, 1161, 1111, 867, 756 cmꢀ1; HRMS (ESIꢀ
TOF, m/z): calcd for C17H13N2O2 [M + H]+ 277.0972, found 277.0979.
2-(4-Chlorophenyl)-9-methyl-4H-pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 5cb. Cream
colored solid (0.053 g, 42%); MP 284 ‒ 286 °C; 1H NMR (400 MHz, CDCl3) δ 9.31 (d, J = 6.7
Hz, 1H), 7.96 – 7.87 (m, 2H), 7.79 (d, J = 9.1 Hz, 1H), 7.71 – 7.61 (m, 1H), 7.57 – 7.50 (m, 2H),
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7.20 (td, J = 6.9, 1.0 Hz, 1H), 6.88 (s, 1H); C NMR (100 MHz, CDCl3) δ 170.1, 160.6, 159.5,
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144.7, 137.4, 129.9, 129.7, 129.4, 127.5, 127.0, 126.2, 114.2, 109.8, 16.9; FTꢀIR vmax (neat)
3084, 1656, 1608, 1434, 1256, 1111, 1056, 756 cmꢀ1; HRMS (ESIꢀTOF, m/z): calcd for
C17H12ClN2O2 [M + H]+ 311.0582, found 311.0586.
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7-(4-Chlorophenyl)-2-phenyl-4H-pyrano[2',3':4,5]imidazo[1,2-a]pyridin-4-one 5ea. Viscous
liquid (0.060 g, 35%); 1H NMR (400 MHz, CDCl3) δ 9.49 (s, 3H), 8.00 (d, J = 2.7 Hz, 1H), 7.98
(d, J = 3.3 Hz, 1H), 7.86 (d, J = 1.6 Hz, 2H), 7.62 (d, J = 8.5 Hz, 3H), 7.59 – 7.55 (m, 3H), 7.52
(d, J = 8.5 Hz, 2H), 6.93 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 170.4, 161.3, 161.0, 146.6,
143.6, 134.7, 134.6, 134.6, 131.3, 130.5, 129.5, 129.1, 128.4, 127.6, 126.3, 125.6, 116.9, 109.7;
FTꢀIR vmax (neat) 3062, 2924, 2854, 1643, 1631, 1577, 1465, 1261, 1091, 817, 694 cmꢀ1; HRMS
(ESIꢀTOF, m/z): calcd for C22H14ClN2O2 [M + H]+ 373.0738, found 373.0744.
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N-(5-Phenylpyridin-2-yl)acetamide 7d.40 Cream solid (0.021 g, 18%); H NMR (400 MHz,
CDCl3) δ 8.83 (s, 1H), 8.52 (s, 1H), 8.32 (d, J = 8.5 Hz, 1H), 7.95 (dd, J = 8.6, 2.2 Hz, 1H), 7.59ꢀ
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7.56 (m, 2H), 7.49 (t, J = 7.5 Hz, 2H), 7.44 – 7.35 (m, 1H), 2.26 (s, 3H); C NMR (100 MHz,
CDCl3) δ 164.0, 145.9, 141.0, 132.6, 132.2, 128.1, 124.3, 123.0, 122.0, 109.2, 20.0; FTꢀIR vmax
(neat) 3240, 3039, 2924, 1658, 1527, 1373, 1303, 1018, 763 cmꢀ1.
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N-(5-(4-Chlorophenyl)pyridin-2-yl)acetamide 7e. Cream solid (0.020 g, 15%); H NMR (400
MHz, CDCl3) δ 8.47 (s, 1H), 8.32 (s, 1H), 8.30 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.50
(d, J = 7.2 Hz, 2H), 7.45 (d, J = 7.8 Hz, 2H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
168.67, 150.71, 145.75, 136.72, 135.85, 133.99, 131.73, 129.26, 127.99, 113.79, 24.79; FTꢀIR
vmax (neat) 3242, 3037, 2923, 1657, 1524, 1371, 1305, 1011, 761 cmꢀ1; HRMS (ESIꢀTOF, m/z):
calcd for C13H11ClN2O [M + H]+ 246.0560, found 246.0558.
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2-Phenylimidazo[1,2-a]pyridine 11.41 Cream coloured solid (0.018, 10%); H NMR (400 MHz,
CDCl3) δ 8.12 (dt, J = 6.8, 1.2 Hz, 1H), 8.02 – 7.95 (m, 2H), 7.87 (s, 1H), 7.65 (dq, J = 9.1, 1.1
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Hz, 1H), 7.51 – 7.41 (m, 2H), 7.39 – 7.32 (m, 1H), 7.18 (ddd, J = 9.1, 6.7, 1.3 Hz, 1H), 6.78 (td,
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J = 6.7, 1.2 Hz, 1H); C NMR (100 MHz, CDCl3) δ 145.8, 145.7, 133.8, 128.7, 127.9, 126.0,
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125.5, 124.6, 117.5, 112.4, 108.1.
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Conflict of interest
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The authors declare no conflict of interest
Supporting information
Supporting information (copies of NMR data for 1aꢀf, 2h, 4c, 3aaꢀ3ef, 5aaꢀ5ea and 7dꢀe, HRMS
analysis of reaction mixture) for this article is available.
Acknowledgements
Financial support from Science and Engineering Research Board (SERB), New Delhi [Project
EMR/2016/002242] to carry out this work, DSTꢀFIST [SR/FST/CSIꢀ270/2015] for HRMS
facility and BITS Pilani for single crystal XRD facility is highly acknowledged. KP is thankful to
UGC New Delhi for the senior research fellowship (SRF).
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