Cu-Mn spinel oxide catalyzed synthesis of imidazo[1,2-a]pyridines through domino three-component coupling and 5-exo-dig cyclization in water

Article abstract of DOI:10.1039/c3ra42046a

An efficient and eco-friendly synthesis of therapeutically important and structurally diverse imidazo[1,2-a]pyridines using recyclable bimetallic Cu-Mn spinel oxide catalyst in aqueous medium has been developed. The Cu-Mn catalyzed domino three-component

Full text of DOI:10.1039/c3ra42046a

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PAPER
Cu-Mn spinel oxide catalyzed synthesis of imidazo[1,2-a]pyridines
through domino three-component coupling and 5-exo-dig cyclization in
water#¤
Jaideep B. Bharate,ab Santosh K. Guru,c Shreyans K. Jain,bd Samdarshi Meena,bd Parvinder Pal Singh,ab
5
Shashi Bhushan,bc Baldev Singh,bc Sandip B. Bharateab* and Ram A. Vishwakarmaabd
*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
An efficient and eco-friendly synthesis of therapeutically important and structurally diverse
imidazo[1,2-a]pyridines using recyclable bimetallic Cu-Mn spinel oxide catalyst in aqueous
10 medium have been developed. The Cu-Mn catalyzed domino three-component coupling of 2-
aminopyridine, aldehyde and alkyne followed by 5-exo-dig cycloisomerization produced
desired imidazo[1,2-a]pyridines in good yields. The efficiency of this protocol could be
attributed to the presence of these metals in multiple oxidation states (Cu+2, Mn+2, Mn+3 and
Mn+4) in bimetallic Cu-Mn catalyst. The advantages of this protocol over previous reports
15 include the use of aqueous medium, recyclable catalyst, shorter reaction times and no
requirement of any additive. This is the first method for synthesis of imidazo[1,2-a]pyridines
which utilizes water as a reaction medium.
Due to biological importance of this scaffold, several methods
30 have been developed for their synthesis,2 many of which are
2h-q
Introduction
elegant multi-component approaches.2b,
A three-component
coupling (3CC) of 2-aminopyridine, aldehyde and alkyne in
presence of metal catalyst and/or additive is one of the most
attractive method for synthesis of imidazo[1,2-a]pyridine
35 scaffold.2h-m Various catalysts employed for this 3CC protocol
20 Imidazo[1,2-a]pyridine1 scaffold represents an important class of
biologically active compounds1 and is a core structure of several
drug molecules such as zolpidem (anxiolytic, 1a), olprinone
(cardiotonic, 1b) and minodronic acid (for osteoporosis, 1c) etc.
(Figure 1).
include CuI/NaHSO4-Silica,2h CuCl/Cu(OTf)2, CuSO4/TsOH,2j
2i
InBr3/Et3N,,2k Cu-MOFs,2l and CuSO4/glucose.2m In addition, Liu
and coworkers3 reported synthesis of imidazo[1,2-a]pyridines via
tandem amination/cycloisomerization of aryl propargylic alcohols
40 with 2-aminopyridines using ZnCl2/CuCl catalytic system. These
methods suffers from one or other drawbacks such as use of
homogeneous catalysts, requirement of anhydrous conditions, and
need of additive (such as TsOH,2j Et3N,,2k and glucose2m) in
addition to the metal catalyst. The only report on heterogeneous
45 catalyst for this 3CC is the use of Cu-MOFs, however this
protocol2l requires the use of anhydrous toluene as a reaction
medium and furthermore the substrate scope has not been
explored. Thus, the development of a hazard-free, waste-free,
energy-efficient green protocol is highly desirable for an
50 economical synthesis of this class of compounds.
OH
N
CN
O
OH
Cl
P
O
N
OH
OH
OH
Cl
P
HN
O
N
N
O
N
N
N
1a
1c
1b
25
Figure 1. Examples of imidazo[1,2-a]pyridine containing drugs
aMedicinal Chemistry Division, Indian Institute of Integrative Medicine
(CSIR), Canal Road, Jammu-180001, India
In recent years, bimetallic catalysts have been extensively used as
efficient recyclable catalysts for various organic transformations
bAcademy and Scientific and Industrial Research (AcSIR), Anusandhan
Bhawan, 2 Rafi Marg, New Delhi-110001, India
such
as bimetallic Mg-Fe for synthesis of
α-
hydroxyphosphonates,2a Ir-Pd for alkylation of 1,3-
55 dimethylbarbituric acids,4 Cu-Ni and Cu-Co catalysts for
selective hydrogenation of furfuraldehyde,5 Cu-Mn for
regioselective halogenation of phenols,5 selective ortho-
methylation of phenols,6 and ligand-free Huisgen [3+2]
cycloaddition reaction.4 In continuation to our efforts towards
60 development of efficient synthetic methodologies for preparation
of biologically important scaffolds,6-7 herein we report recyclable
cCancer Pharmacology Division, Indian Institute of Integrative Medicine
(CSIR), Canal Road, Jammu-180001, India
dNatural Products Chemistry Division, Indian Institute of Integrative
Medicine (CSIR), Canal Road, Jammu-180001, India
*E-mail: ram@iiim.ac.in; sbharate@iiim.ac.in
¤ IIIM Publication number IIIM/1554/2013
Fax: +91-191-2569333; Tel: +91-191-2569111
#Electronic supplementary information (ESI) available: NMR spectras of
new compounds. See DOI: 10.1039/xxxx
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

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Cu-Mn spinel oxide catalyzed synthesis of imidazo[1,2-
Table 1. Optimization of reaction conditions for synthesis of
imidazo[1,2-a]pyridines.
a]pyridines under aqueous conditions (Figure 2). Although there
exists numerous Cu-catalyzed methods for this 3CC, all these
methods requires dry solvents and an additive. The advantages of
this protocol include the use of water as a reaction medium, no
need of additive, recyclable catalyst, shorter reaction times and
good yields.
CHO
N
NH2
5
Catalyst
Solvent
+
+
N
N
5a
2a
3a
4a
8
1
7
N
NH2
+
2
Catalysta (mol%)
Solvent
Temp
(°C)
80
Time
(h)
4
Yield
b (%)
0
Ar
R1
Entry
Ar CHO
N
6
10 mol% Cu: Mn (2: 0.25)
Water, 100 oC, 4 h
4
3
N
5
R1
1
2
Clay-Cu(II) (10)
Clay-Cu(II)(10)
NaN3 (20)
EtOH
EtOH
2
3
Recyclable catalyst
Yields = 70-90%
+
80
4
0
R2
R2
+
5
3
4
5
6
Cu-Mn – A (10)
Cu-Mn – B (10)
Cu-Mn – C (10)
Cu-Mn – B (10) + EtOH
glucose (20)
Cu-Mn – B (10)
Cu-Mn – B (10)
Cu-Mn – B (10)
EtOH
EtOH
EtOH
80
80
80
80
4
4
4
4
<10
82
50
55
Imidazo[1,2-a]pyridines
4
Figure 2. Synthesis of imidazo[1,2-a]pyridines using recyclable
10 Cu-Mn bimetallic catalyst in water
7
8
9
ACN
90
100
90
6
4
4
70
85
82
Water
EtOH:
Water
(1:1)
Results and discussion
To develop an efficient green protocol for synthesis of
imidazo[1,2-a]pyridines, various Cu-based heterogeneous
15 catalysts were investigated. The reaction between 2-
aminopyridine (2a), benzaldehyde (3a) and phenyl acetylene (4a)
was used as a model reaction (Table 1). The catalyst screening
was started with the Clay supported Cu(II),6 which did not
produced desired product (entries 1 and 2). Next, we screened
20 various bimetallic Cu-Mn catalysts varying in the composition
(Cu-Mn A: Cu: Mn = 2: 0.25; Cu-Mn B: Cu: Mn = 1: 0.25; and
Cu-Mn C: Cu: Mn = 3: 0.25) using ethanol as a reaction medium.
Among these three Cu-Mn catalysts, Cu: Mn A catalyst produced
imidazo[1,2-a]pyridine 5a only in <10% yield (entry 3), however
25 Cu-Mn B and Cu: Mn C catalysts produced 5a in 82 and 50%
yields, respectively (entries 4 and 5). Addition of additive to the
reaction medium (e.g. reducing agent) led to decrease in the
reaction yield (entry 6). The solvent optimization studies (entries
7-10) identified water as the best solvent producing higher yields
30 (entry 8). Increase in the catalyst leading from 10 to 100 mol%
(entries 8, 11-13) led to increase in the yield, however 10 mol%
loading was found to be efficient (entry 8) producing 85% yield
of the product.
10
Cu-Mn – B (10)
ACN:
Water
(1:1)
Water
Water
Water
Water
Water
Water
EtOH
90
4
74
11
12
13
14
15
16
17
Cu-Mn – B (20)
Cu-Mn – B (50)
Cu-Mn – B (100)
CuCl2 (10)
MnCl2 (10)
CuCl2 (10)
CuCl2
(10)+MnCl2(10)
CuCl2(10)+MnCl2
(10)
CuCl/ Cu(OTf)2
CuCl/ Cu(OTf)2
100
100
100
100
100
100
90
4
4
4
4
4
10
12
82
85
90
30
0
30
35
18
Water
100
12
38
19
20
water
toluene
100
100
4
4
55
78
55 a Cu-Mn catalysts A-C vary in their composition. A: Cu: Mn = 2:
0.25; B: Cu: Mn = 1: 0.25; C: Cu: Mn = 3: 0.25.
b Isolated yield after silica gel column chromatography.
Next, we studied the scope of this MCR protocol for various
60 substituted aminopyridines, benzaldehydes and phenyl
acetylenes. The 2-aminopyridine (2a) and EWG or EDG
substituted 2-aminopyridines participated well in this reaction as
depicted in Figure 3, 4 and 5, respectively. The 2-aminopyridine
(2a) on treatment with various aldehydes and phenyl acetylenes
65 produced corresponding imidazo[1,2-a]pyridines 5a-j in 72-85%
yields (Figure 3). The 2-aminopyridine substituted with EWG
(such as halogens) or EDG (such as methyl) produced
corresponding products 5k-t and 5u-w in 76-90% and 70-83%
yields, respectively (Figure 4 and 5). Similarly, benzaldehydes
70 with both EWGs (e.g. Cl, F) as well as EDGs (e.g. OMe)
participated in this MCR protocol. The heterocyclic aldehydes
produced desired products in good yields (e.g. 5c, 5p, 5v and
5w). Notably, the sterically hindered substrates such as 2-
chlorobenzaldehyde (examples 5b and 5w) also participated
75 effectively in this 3CC to afford respective products. The phenyl
acetylene as well as substituted phenyl acetylenes produced
corresponding imidazo[1,2-a]pyridines in good yields. Notably
the sterically hindered phenyl acetylene viz. 2-chloro-phenyl
acetylene also participated well in this 3CC producing
80 corresponding product 5j in 75% yield.
As a control experiment, the catalytic activity of CuCl2 and
35 MnCl2 salts (entries 14-19) was also investigated using optimized
protocol. Reaction moved only with CuCl2 (30% yield; entry 14)
and not with MnCl2 (entry 15). Further, when CuCl2 (10 mol%)
and MnCl2 (10 mol%) were used together for this 3CC, there was
no significant improvement in the yield of 5a (entries 17-18).
40 These results clearly indicated the significance of combining Cu
and Mn metals in the form of bimetallic heterogeneous Cu-Mn
2i
spinel oxide. Next, we tested CuCl/Cu(OTf)2 for this 3CC. As
reported earlier,2i it produced 5a in good yield when toluene was
used as a solvent (entry 20). When CuCl/Cu(OTf)2 catalyzed 3CC
45 was carried out in water, product 5a was still formed, but only in
55% yield. Thus, after numerous optimization experiments, we
chose 10 mol% of Cu-Mn – B in water (entry 8, Table 1) as a
optimized reaction condition for further studies.
50
2
| Journal Name, [year], [vol], 00–00
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1
NH2
+
8
5
The recyclability of Cu-Mn B catalyst was checked to prove the
heterogeneous nature and its repeated use. The reaction of 2-
aminopyridine (2a), benzaldehyde (3a) and phenylacetylene (4a)
in water in presence of 10 mol% Cu-Mn B led to the formation of
15 3-benzyl-2-phenyl-imidazo[1,2-a]pyridine (5a) in 85, 80, 78,
76% yield over four cycles respectively. In this recyclability
study, catalyst was recovered by filtration after each experiment.
The SEM image of the used bimetallic catalyst showed similar
morphology and the structural integrity after 4th run, which
20 clearly indicated that the Cu-Mn catalyst is robust, recyclable and
was not affected under the reaction conditions of this MCR
protocol. The % of catalyst receovered after each run and % yield
of the product is depicted in the Figure 6.
7
6
N 2
Ar CHO
N
Ar
10 mol% Cu: Mn B
Water, 100 oC, 4 h
N
3
4
2a
R2
3
+
R2
4
5a-j
Cl
N
N
N
N
N
OMe
N
N
O
N
5d (77%)
5c (80%)
5a (85%)
5b (78%)
Cl
F
F
F
F
N
N
N
N
N
N
% Catalyst recovery
% Yield of product
100
80
60
40
20
0
MeO
5f (72%)
5g (76%)
5e (76%)
N
N
N
N
N
Cl
Cl
Cl
N
Cl
5j (75%)
Br
5h (80%)
5i (78%)
Figure 3. Substrate scope for 3CC of 2-aminopyridine (2a) with
various aldehydes and phenyl acetylenes
1
2
3
4
1
NH2
+
8
5
Run
7
6
N 2
3
Ar CHO
N
Ar
10 mol% Cu: Mn B
Water, 100 oC, 4 h
X
N
4
25 Figure 6. Recyclability results of Cu-Mn B catalyst for synthesis of 3-
benzyl-2-phenyl-imidazo[1,2-a]pyridine (5a). The 100 mg of catalyst was
used for first experiment. In each cycle, 10 mol% of catalyst was used.
X
2b-c
3
R2
+
R2
4
5k-t
N
N
In order to understand the efficiency and catalytic activity as a
30 function of catalyst composition, physical nature and surface
acidity, the Cu-Mn catalysts were characterized for specific
surface area, X-ray diffraction pattern, oxidation state (using XPS
analysis) and scanning electron microscopy (SEM) analysis.
Among the three Cu−Mn spinel oxide catalysts (A−C) with
35 varying amount of copper, the best conversion was observed in
Cu-Mn spinel oxide (B). XRD studies of all three Cu-Mn
catalysts indicated that Cu−Mn spinel oxide B shows the
presence of distinct Mn−Cu phases with comparatively less
intensity of tenorite. The presence of distinct Mn−Cu phases in
40 the form of near spherical nanoparticles and comparatively larger
surface area (49.79 m2/g) of Cu−Mn spinel oxide (B) might be
responsible for enhanced yield. The oxidation states of both
metals in Cu-Mn catalyst B was determined by XPS analysis.
Figure 7a shows the high resolution narrow scans of Mn 2p for
45 Cu-Mn catalyst B. The observed spin-orbit splitting between the
two main peak positions of Mn – Mn 2p3/2 and Mn2p1/2 could be
deconvoluted into three peaks each and the distance between
them was ~ 12 eV.8 The observed binding energy peaks are broad
and asymmetric, which suggests the coexistence of Mn in
50 multivalent states as Mn2+, Mn3+ and Mn4+ ions. The asymmetric
index β value was found to be 1.36, which is the evidence for the
multiplet splitting of the Mn 2p level.9 Figure 7b shows the high
resolution narrow scans of Cu 2p for Cu-Mn catalyst B. The
observed binding energy peaks at ~ 934 eV and ~ 955 eV are due
55 to Cu 2p3/2 and Cu 2p1/2, respectively and can be attributed to Cu
in +2 oxidation state. Thus, the XPS analysis indicated that the
Cu exists in Cu2+ oxidation state and Mn in the multi-states
(Mn2+, Mn3+ and Mn4+). Thus, the improved efficiency of Cu and
Mn metals when combined in the form of bimetallic catalyst,
60 over individual metals (Table 1, entries 14-18) could be attributed
to the existence of these metals in multiple oxidation states (Cu+2,
Mn+2, Mn+3 and Mn+4) in bimetallic Cu-Mn catalyst. The possible
N
N
Cl
Cl
Cl
N
N
OMe
N
Cl
F
N
Cl
5k (90%)
5l (85%)
5m (77%)
5n (76 %)
F
N
N
N
Br
N
N
Cl
N
O
Cl
Cl
F
5p (76%)
5q (90%)
5o (77%)
F
F
N
N
N
N
N
OMe
N
F
O
F
F
5r (82%)
5t (82%)
5s (76%)
5
Figure 4. Substrate scope for 3CC of 5-halo substituted 2-
aminopyridines 2b-c with various aldehydes and phenyl
acetylenes
CH3
CH3
8
1
NH2
7
N 2
Ar CHO
+
N
Ar
R1
10 mol% Cu: Mn B
Water, 100 oC, 4 h
N
6
3
4
5
2d
R2
3
+
R2
4
5u-w
CH3
N
CH3
CH3
F
F
Cl
N
N
N
N
N
O
5u (77%)
5w (70%)
5v (83%)
Figure 5. Substrate scope for 3CC of 3-methyl 2-aminopyridine
10 (2d) with various aldehydes and phenyl acetylenes
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DOI: 10.1039/C3RA42046A
mechanism for Cu-Mn catalyzed domino three-component 45 resulting mixture was refluxed at 100 °C for 4 h. Completion of
coupling and 5-exo-dig cyclization is depicted in section S4 of
ESI.
the reaction was monitored by TLC. Reaction mixture was
filtered through Whatman filter paper, residue washed with water
(25 mL x 3). The product was extracted from the aqueous filtrate
with methylene chloride. Combined organic layers were
50 concentrated on vacuo rotavapor to get crude product, which was
purified by column chromatography on neutral alumina (100−300
mesh) using EtOAc/hexane as mobile phase, to get products 5a-w
in 70-90% yield. Compounds 5a,2j, 2m 5b,3 5c,2k 5d,3 5f,2k 5k2m
and 5m2m were characterized by comparison of their spectral data
55 with literature values. Spectral data for all compounds is provided
below.
2m
3-Benzyl-2-phenyl-imidazo[1,2-a]pyridine (5a):2j,
Brown
1
crystalline solid; m.p. 153-154 °C; H NMR (CDCl3, 400 MHz):
δ 7.80-7.78 (m, 2H), 7.70-7.67 (m, 2H), 7.43 (t, J = 6.6 Hz, 2H),
60 7.37-7.27 (m, 4H), 7.20-7.16 (m, 3H), 6.71 (t, J = 6.8 Hz, 1H),
4.50 (s, 2H); 13C NMR (CDCl3, 100 MHz): δ 144.8, 144.0,
136.7, 135.8, 129.1, 128.7, 128.2, 127.8, 127.7, 127.0, 124.3,
123.5, 117.7, 117.5, 112.3, 29.8; IR (CHCl3): νmax 3400, 3058,
3027, 2850, 1632, 1602, 1503, 1493, 1359, 1271 cm-1; ESI-MS:
65 m/z 285.20 [M+H+]; HRMS (ESI): HRMS: m/z 285.1388 calcd
for C20H16N2 + H+ (285.1386).
(a)
(b)
Figure 7. High resolution narrow X-ray photoelectron spectra
(XPS) for Cu-Mn catalyst B
5
All imidazo[1,2-a]pyridines were screened for anti-proliferative
activity against a panel of cancer cell lines. Among tested
analogs, compounds 5e, 5n and 5r showed moderate cytotoxicity
10 towards MIAPaCa-2, PC-3, HL-60 and A549 cell lines (20-38%
growth inhibition at 10 µM; see section S3 of ESI).
3-Benzyl-2-(2-chlorophenyl)-imidazo[1,2-a]pyridine
(5b):3
Brown crystalline solid; m.p. 112-113 °C; H NMR (CDCl3, 400
MHz): 7.69-7.66 (m, 2H), 7.56-7.53 (m, 1H) 7.50-7.48 (m, 1H)
1
δ
70 7.34-7.31 (m, 2H) 7.24 (d, J = 7.8 Hz, 2H), 7.20-7.15 (m, 2H),
7.07 (d, J = 4.0 Hz, 2H), 6.69 (t, J = 8.0 Hz, 1H), 4.28 (s, 2H);
13C NMR (CDCl3, 125 MHz): δ 144.6, 142.1, 136.5, 133.5,
132.6, 129.8, 129.6, 128.8, 127.9, 126.8, 126.7, 124.2, 123.8,
117.6, 112.3, 30.1; IR (CHCl3): νmax 3391, 3060, 2923, 2852,
75 1633, 1494, 1501, 1387, 1361, 1041 cm-1; ESI-MS: m/z 319.10
[M+H]+; HRMS: m/z 319.1001 calcd for C20H15ClN2 + H+
(319.0997).
Conclusion
In summary, we have developed simple and efficient Cu-Mn
catalyzed green protocol for synthesis of structurally diverse
15 medicinally important imidazo[1,2-a]pyridines. This protocol is
superior to all known protocols as it involves the use of
recyclable catalyst and water as a reaction medium and does not
require any additive. Thus, the developed method finds wide
utility in economical and environment-friendly synthesis of this
20 class of compounds.
3-Benzyl-2-(furan-2-yl)-imidazo[1,2-a]pyridine (5c):2k Brown
1
crystalline solid; m.p. 101-102 °C; H NMR (CDCl3, 400 MHz):
80 δ 7.73 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.49 (s, 1H),
7.28-7.14 (m, 6H), 6.92 (d, J = 4.1 Hz, 1H), 6.68 (t, J = 8.0 Hz,
1H), 6.52-6.51 (m, 1H), 4,56 (s, 2H); 13C NMR (CDCl3, 125
MHz): δ 150.3, 145.0, 142.1, 136.7, 135.3, 128.5, 128.1, 126.6,
124.3, 122.8, 118.1, 117.5, 112.2, 111.2, 107.4, 29.7; IR (CHCl3):
85 νmax 3391, 2918, 1602, 1635, 1452, 1494, 1352, 1195, 1009 cm-1;
ESI-MS: m/z 275.10 [M+1]; HRMS: m/z 275.1181 calcd for
C18H14N2O + H+ (275.1179).
Experimental section
General information. All chemicals were obtained from Sigma-
1
Aldrich Company and used as received. H, 13C and DEPT NMR
spectra were recorded on Brucker-Avance DPX FT-NMR 500
25 and 400 MHz instruments. Chemical data for protons are reported
in parts per million (ppm) downfield from tetramethylsilane and
are referenced to the residual proton in the NMR solvent (CDCl3,
7.26 ppm). Carbon nuclear magnetic resonance spectra (13C
NMR) were recorded at 125 MHz or 100 MHz: chemical data for
30 carbons are reported in parts per million (ppm, δ scale) downfield
from referenced to the carbon resonance of the solvent (CDCl3,
77 ppm). ESI-MS and HRMS spectra were recorded on Agilent
1100 LC-Q-TOF and HRMS-6540-UHD machines. IR spectra
were recorded on Perkin-Elmer IR spectrophotometer. Melting
35 points were recorded on digital melting point apparatus. XRD
spectra and Scanning electron micrograph were obtained on XRD
Mini-Flex Rigaku Model and Jeol.JEM100C-XII electron
microscope respectively. XPS analysis was performed on a
KRATOS-AXIS 165 instrument.
3-Benzyl-2-(4-methoxyphenyl)-imidazo[1,2-a]pyridine (5d):3
1
White crystalline solid; m.p. 135-136°C; H NMR (CDCl3, 400
90 MHz): δ 7.76 (m, 4H), 7.33-7.28 (m, 4H), 7.18 (m, 2H), 7.00 (d,
J = 4.1 Hz, 2H), 6.77 (m, 1H), 4.51 (s, 2H), 3.87 (s, 3H); IR
(CHCl3): νmax 3400, 2923, 2853, 1742, 1613, 1502, 1453, 1248,
1023 cm-1; ESI-MS: m/z 315.10 [M+1]+; HRMS: m/z 315.1495
calcd for C21H18N2O + H+ (315.1492).
95 3-Benzyl-2-(3,5-difluorophenyl)-imidazo[1,2-a]pyridine (5e):
1
White solid; m.p. 141-142 °C; H NMR (CDCl3, 400 MHz): δ
7.77-7.71 (m, 2H), 7.36-7.31 (m, 6H), 7.15 (d, J = 8.0 Hz, 2H),
6.84-6.77 (m, 2H), 4.52 (s, 2H); 13C NMR (CDCl3, 125 MHz): δ
163.0 (d, JCF = 265.4 Hz), 145.3, 144.2, 136.9, 135.5, 129.3,
1
2
100 127.5, 127.1, 123.4, 118.8, 118.4, 117.4, 113.3, 111.2 (d, JCF
=
26.4 Hz), 103.1 (t, 2JCF = 52.6 Hz), 28.8; 19F NMR (376.50 MHz,
CDCl3): δ -109.14 (t, J = 3.8 Hz, 2F); IR (CHCl3): νmax 3400,
3034, 2922, 1625, 1595, 1494, 1431, 1390, 1238, 1116 cm-1; ESI-
MS: m/z 321.20 [M+1]+); HRMS: m/z 321.1200 calcd for
105 C20H14F2N2 + H+ (321.1198).
40 General procedure for synthesis of imidazo[1,2-a]pyridines
5a-w: The mixture of 2-aminopyridine (2, 1 mmol) and
benzaldehyde (3, 1 mmol) was stirred for 15 min. Water (3 mL)
was added, followed by addition of phenyl acetylene (4, 1.5
mmol). Then, Cu-Mn catalyst (10 mol %) were added, and
4
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3-Benzyl-2-(3-chlorophenyl)-imidazo[1,2-a]pyridine
1
(5f):2k
White crystalline solid; m.p. 137-138 °C; H NMR (CDCl3, 400
3-Benzyl-2-(4-chlorophenyl)-6-fluoro-imidazo[1,2-a]pyridine
1
(5l): Cream colored solid; m.p. 193-194 °C; H NMR (CDCl3,
MHz): δ 7.79-7.75 (m, 2H), 7.70 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 65 400 MHz): δ 7.73 (d, J = 8.0 Hz, 2H), 7.69-7.66 (m, 2H), 7.44 (d,
4.0 Hz, 1H), 7.31-7.19 (m, 6H), 7.07 (d, J = 8.0 Hz, 2H), 6.75 (t,
J = 8.0 Hz, 1H), 4.43 (s, 2H); IR (CHCl3): νmax 3435, 2923, 2852,
1734, 1601, 1494, 1453, 1361, 1249, 1079 cm-1; ESI-MS: m/z
319.10 [M+1]+; HRMS: m/z 319.1001 calcd for C20H15ClN2 + H+
(319.0997).
J = 8.0 Hz, 2H), 7.35-7.28 (m, 3H), 7.15 (m, 3H), 4.45 (s, 2H);
13C NMR (CDCl3, 125 MHz): δ 153.4 (d, 1JCF = 237.7 Hz), 144.1,
142.4, 135.7, 134.1, 132.4, 129.3, 129.0, 127.6, 127.3, 119.4,
118.0, 117.9, 116.8 (d, 2JCF = 25.2 Hz), 110.2 (d, 2JCF = 41.5 Hz),
70 29.9; 19F NMR (376.50 MHz,CDCl3) δ -139.22 (s, 1F); IR
(CHCl3): νmax 3400, 3043, 2924, 1651, 1572, 1510, 1534, 1488,
1370, 1195, 1147, 1014 cm-1 ESI-MS: m/z 337.00 [M+1]+;
HRMS: m/z 337.0909 calcd for C20H14ClFN2 + H+ (337.0902).
5
2-(3,5-Difluorophenyl)-3-(4-Methoxybenzyl)-imidazo[1,2-
1
10 a]pyridine (5g): Yellow crystalline solid; m.p. 135-136 °C; H
NMR (CDCl3, 400 MHz): δ 7.75 (d, J = 8.0 Hz, 1H), 7.68 (d, J =
8.0, 1H), 7.34 (d, J = 4.0 Hz, 2H), 7.22 (t, J = 8.0 Hz, 1H), 7.03
3-Benzyl-6-chloro-2-phenyl-imidazo[1,2-a]pyridine
1
(5m):2m
(d, J = 4.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 6.79-6.74 (m, 2H), 75 Cream colored solid; m.p. 172-173 °C; H NMR (CDCl3, 400
4.43 (s, 2H), 3.78 (s, 3H); 13C NMR (CDCl3, 125 MHz): δ 162.6
15 (d, JCF = 242.7 Hz), 158.1, 144.0, 140.3, 136.8, 128.4, 127.2,
MHz): δ 7.69 (m, 3H), 7.61 (d, J = 8.0 Hz, 1H), 7.37 (t, J = 8.0
Hz, 2H), 7.32-7.19 (m, 4H), 7.12-7.06 (m, 3H), 4.36 (s, 2H); 13C
NMR (CDCl3, 125 MHz): δ 142.8, 134.2, 129.2, 128.9, 128.7,
128.2, 128.1, 128.1, 127.8, 127.6, 127.5, 127.2, 126.2, 122.5,
1
2
124.7, 123.0, 118.5, 117.1, 113.9, 112.1, 110.2 (d, JCF = 20.1
Hz), 102.7 (t, 2JCF = 52.8 Hz), 54.5, 28.6; 19F NMR (376.50 MHz,
CDCl3): δ -109.60 (t, J = 7.5 Hz, 2F); IR (CHCl3): νmax 3400, 80 121.2, 119.3, 118.1, 115.7, 29.8; IR (CHCl3): νmax 3400, 3082,
2922, 2849, 1730, 1625, 1596, 1511, 1433, 1390, 1363, 1247,
20 1034 cm-1; ESI-MS: m/z 351.10 [M+1]+; HRMS: m/z 351.1309
calcd for C21H16F2N2O + H+ (351.1304).
2921, 2851, 1738, 1603, 1521, 1493, 1449, 1325, 1251, 1094 cm-
1; ESI-MS: m/z 319.10 [M+1]+; HRMS: m/z 319.1001 calcd for
C20H15ClN2+H+ (319.0997).
2-(4-Chlorophenyl)-3-(3-Methylbenzyl)-imidazo[1,2- 3-Benzyl-6-chloro-2-(4-methoxyphenyl)-imidazo[1,2-
a]pyridine (5h): Brown sticky solid; m.p. 129-130 °C; H NMR 85 a]pyridine (5n): Yellow crystalline solid; m.p. 166-167 °C; H
1
1
(CDCl3, 400 MHz): δ 7.65-7.58 (m, 2H), 7.32 (d, J = 12.0 Hz,
25 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.11 (t, J = 8.0 Hz, 2H), 6.99 (d, J
= 8.0 Hz, 2H), 6.86-6.81 (m, 2H), 6.63 (t, J = 4.0 Hz, 1H), 4.34
(s, 2H), 2.20 (s, 3H); 13C NMR (CDCl3, 125 MHz): δ 145.1
142.8, 138.9, 136.4, 133.7, 133.5, 131.3, 129.3, 129.0, 128.9,
128.3, 127.8, 124.6, 124.5, 123.4, 117.1, 112.4, 29.5, 21.3; IR
30 (CHCl3): νmax 3434, 2922, 1740, 1619, 1464, 1219, 1020 cm-1;
ESI-MS: m/z 333.00 [M+1]+; HRMS: m/z 333.1141 calcd for
C21H17ClN2 + H+ (333.1153)
NMR (CDCl3, 400 MHz): δ 7.73 (m, 3H), 7.63 (d, J = 8.0 Hz,
1H), 7.35-7.28 (m, 3H), 7.15 (m, 3H), 6.99 (d, J = 8.0 Hz, 2H),
4,45 (s, 2H), 3.84 (s, 3H); 13C NMR (CDCl3, 125 MHz): δ 160.2,
144.9, 143.0, 136.1, 129.5, 129.2, 127.7, 127.1, 126.5, 121.1,
90 120.7, 117.7, 117.5, 114.2, 55.1, 29.6; IR (CHCl3): νmax 3400,
2921, 2850, 1611, 1577, 1500, 1453, 1325, 1249, 1041, 1029 cm-
1; ESI-MS: m/z 349.00 [M+1]+; HRMS: m/z 349.1105 calcd for
C21H17ClN2O + H+ (349.1102).
3-Benzyl-2-(4-bromophenyl)-6-chloro-imidazo[1,2-a]pyridine
1
95 (5o): White crystalline solid; m.p. 118-119 °C; H NMR (CDCl3,
3-(4-Bromobenzyl)-2-(4-chlorophenyl)-imidazo[1,2-a]pyridine
1
(5i): Yellow sticky solid; H NMR (CDCl3, 400 MHz): δ 7.69-
400 MHz): δ 7.78 (s, 1H), 7.71-7.65 (m, 3H), 7.59 (d, J = 8.0 Hz,
2H), 7.38-7.27 (m, 3H), 7.23 (d, J = 8.0 Hz, 1H), 7.14 (d, J = 8.0
Hz, 2H), 4.47 (s, 2H); 13C NMR (CDCl3, 125 MHz): δ 143.6,
142.9, 135.7, 132.5, 131.9, 129.6, 129.3, 127.51, 127.2, 126.3,
100 122.6, 121.3, 121.0, 118.3, 117.7, 29.5; IR (CHCl3): νmax 3400,
2921, 2851, 1742, 1601, 1521, 1423, 1343, 1399, 1020 cm-1; ESI-
MS: m/z 396.9 [M+1]+; HRMS: m/z 397.0102 calcd for
C20H14BrClN2 + H+ (397.0102).
35 7.65 (m, 4H), 7.44-7.41 (dd, J = 8.0, 12.0 Hz, 4H), 7.22 (t, J =
8.0 Hz, 1H), 7.00 (d, J = 8.0 Hz, 2H), 6.75 (t, J = 8.0 Hz, 1H),
4.41 (s, 2H); 13C NMR (CDCl3, 125 MHz): δ 145.9, 144.1, 136.5,
134.8 133.8, 133.1, 130.3, 130.2, 129.8, 125.5, 124.1, 121.8,
118.6, 118.0, 113.5, 30.6; IR (CHCl3): νmax 3398, 2922, 1740,
40 1634, 1486, 1464, 1018, 771 cm-1; ESI-MS: m/z 398.90 [M+1]+;
HRMS: m/z 398.7021 calcd for C20H14BrClN2 + H+ (398.7030)
3-Benzyl-6-chloro-2-(furan-2-yl)-imidazo[1,2-a]pyridine (5p):
3-(2-Chlorobenzyl)-2-(4-chlorophenyl)-imidazo[1,2-
1
a]pyridine (5j): Yellow solid; m.p. 105-106 °C; 1H NMR 105 Brown yellow solid; m.p. 149-150 °C; H NMR (CDCl3, 400
(CDCl3, 400 MHz): δ 7.71-7.65 (m, 4H), 7.50 (d, J = 8.0 Hz, 1H),
45 7.40 (d, J = 8.0 Hz, 2H), 7.27-7.23 (dd, J = 8.0, 16.0 Hz, 2H),
7.09 (t, J = 8.0 Hz, 1H), 6.77 (t, J = 8.0 Hz, 1H), 6.71 (d, J = 8.0
Hz, 1H), 4.51 (s, 2H); 13C NMR (CDCl3, 125 MHz): δ 145.1,
143.5, 134.1, 134.0, 133.8, 132.8, 129.9, 129.3, 128.9, 128.5,
128.4, 127.5, 124.7, 123.3, 117.7, 116.7, 112.6, 27.7; IR (CHCl3):
50 νmax 3399, 2923, 1634, 1486, 1467, 1384, 1254, 1038, 749 cm-1;
ESI-MS: m/z 353.00 [M+1]+; HRMS: m/z 353.0615 calcd for
C20H14Cl2N2 + H+ (353.0607)
MHz): δ 7.79 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.53 (s, 1H), 7.33-
7.12 (m, 6H), 6.94 (s, 1H), 6.55 (d, J = 4.0 Hz, 1H), 4.61 (s, 2H);
13C NMR (CDCl3, 125 MHz): δ 149.5, 143.1, 142.3, 136.2,
128.5, 127.9, 126.5, 126.1, 121.0, 120.2, 118.6, 117.2, 111.5,
110 108.1, 29.5; IR (CHCl3): νmax 3400, 2919, 1602, 1520, 1494,
1454, 1403, 1324, 1253, 1070 cm-1; ESI-MS: m/z 308.9 [M+1]+;
HRMS: m/z 309.0795 calcd for C18H13ClN2O + H+ (309.0789).
3-Benzyl-6-chloro-2-(3,5-difluorophenyl)-imidazo[1,2-
a]pyridine (5q): White crystalline solid; m.p. 181-182 °C; H
1
115 NMR (CDCl3, 400 MHz): δ 7.79 (s, 1H), 7.66 (d, J = 8.0 Hz,
3-Benzyl-6-chloro-2-(4-chlorophenyl)-imidazo[1,2-a]pyridine
(5k):2m Brown crystalline solid; m.p. 153-154 °C; 1H NMR
55 (CDCl3, 400 MHz): δ 7.74 (s, 1H), 7.70-7.67 (m, 2H), 7.62 (d, J
= 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.35-7.28 (m, 4H), 7.17-
7.10 (m, 2H), 4.44 (s, 2H); 13C NMR (CDCl3, 125 MHz): δ 143.8,
1H), 7.35-7.02 (m, 8H), 6.82 (brs, 1H), 4.49 (s, 2H); 13C NMR
1
(CDCl3, 125 MHz): δ 163.3 (d, JCF = 240.2 Hz),143.1, 142.5,
137.1, 135.5, 129.38, 127.6, 126.3, 121.4, 121.1, 119.2, 118.1,
2
2
110.9 (d, JCF = 26.4 Hz), 103.3 (t, JCF = 40.0 Hz), 29.5; 19F
143.1, 135.8, 134.1, 132.4, 129.34, 129.29, 128.9, 127.5, 127.3, 120 NMR (376.5 MHz, CDCl3): δ -109.29 (t, J = 7.5 Hz, 2F); IR
125.9, 121.2, 120.8, 118.6, 117.8, 29.6; IR (CHCl3): νmax 3400,
60 2920, 1730, 1601, 1521, 1486, 1402, 1325, 1096 cm-1; ESI-MS:
m/z 353.00 [M+1]+; HRMS: m/z 353.0612 calcd for C20H14Cl2N2
+ H+ (353.0607).
(CHCl3): νmax 3400, 3050, 2850, 1624, 1591, 1522, 1451, 1430,
1387, 1116, 1047 cm-1; ESI-MS: m/z 354.9 [M+1]+; HRMS: m/z
355.0813 calcd for C20H13ClF2N2 + H+ (355.0808).
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1H), 6.58 (t, J = 8.0 Hz, 1H), 4.23 (s, 2H), 2.53 (s, 3H); 13C NMR
(CDCl3, 125 MHz): δ 144.2, 142.4, 136.7, 136.5, 134.1, 132.8,
65 129.7, 128.8, 128.0, 126.7, 121.7, 30.1, 17.3; IR (CHCl3): νmax
3401, 2923, 2856, 1700, 1632, 1578, 1458, 1384, 1026 cm-1; ESI-
MS: m/z 333.0 [M+1]+; HRMS: m/z 333.1156 calcd for
C21H17ClN2 + H+ (333.1153).
3-Benzyl-6-fluoro-2-(4-methoxyphenyl)-imidazo[1,2-
a]pyridine (5r): Cream colored solid; m.p. 156-157 °C; 1H NMR
(CDCl3, 400 MHz): δ 7.74 (d J = 8.0 Hz, 2H),7.68-7.62 (m, 2H),
7.36-7.29 (m, 3H), 7.16-7.06 (m, 3H), 7.00 (d, J = 8.0 Hz, 2H),
4,46 (s, 2H), 3.85 (s, 3H); 13C NMR (CDCl3, 125 MHz): δ 159.5,
5
1
153.2 (d, JCF = 235.0 Hz) 145.2, 142.2, 136.2, 129.3, 129.0,
2
127.6, 127.1, 126.7, 118.4, 117.7, 115.9 (d, JCF = 25.0 Hz),
2
114.2, 109.9 (d, JCF = 30.0 Hz), 55.0, 30.0; 19F NMR (376.50
Preparation and characterization of Cu-Mn catalysts A-C. A
70 series of copper-manganese mixed oxides (A−C) were prepared
by the coaddition of the aqueous solutions of CuCl2·2H2O and
MnCl2·4H2O in a molecular weight ratio (2: 0.25; 1: 0.25; 3:
0.25, respectively) at a rate of 1 mL min−1 under vigorous
mechanical stirring at room temperature to form a uniform
75 solution. Then ammonia solution was added drop by drop until it
reached pH 8.5−8.7 and was allowed to stand overnight to form a
gel, filtered, and washed with double distilled water until free
from chloride ions. After being kept overnight at room
temperature, the cake was allowed to dry in an air oven at 110 °C
MHz, CDCl3): δ -139.84 (s, 1F); IR (CHCl3): νmax 3400, 2921,
10 2853, 1738, 1650, 1611, 1536, 1502, 1370, 1248, 1220, 1046 cm-
1; ESI-MS: m/z 333.0 [M+1]+; HRMS: m/z 333.1402 calcd for
C21H17FN2O + H+ (333.1398).
3-Benzyl-6-fluoro-2-(3,5-difluorophenyl)-imidazo[1,2-
a]pyridine (5s): Cream colored solid; m.p. 145-146 °C; 1H NMR
15 (CDCl3, 400 MHz): δ 7.70-7.66 (m, 2H), 7.37-7.28 (m, 5H),
7.19-7.12 (m, 3H), 6.82 (t, J = 8.0 Hz, 1H), 4,48 (s, 2H); 13C
1
NMR (CDCl3, 125 MHz): δ 163.1 (d, JCF = 247.0 Hz), 153.5 (d,
1JCF = 239.0 Hz), 143.1, 142.4, 137.4, 135.4, 129.1, 127.7, 127.3, 80 for 24 h and finally calcined (10 °C min−1) in a muffle furnace at
120.0, 118.3, 117.0 (d, 2JCF = 26.0 Hz), 110.6 (d, 2JCF = 31.0 Hz),
425 °C for 3 h. Catalysts were adequately characterized to
understand the efficiency of catalytic activity. X-ray diffraction
(XRD), specific surface area, scanning electron micrograph
(SEM) and XPS analysis were studied and are provided in the
2
2
20 110.2 (d, JCF = 41.0 Hz), 103.2 (t, JCF = 26.0 Hz), 29.9; 19F
NMR (376.5 MHz, CDCl3): δ -109.35 (t, J = 7.5 Hz, 2F), -138.64
(s, 1F); IR (CHCl3): νmax 3400, 2920, 2851, 1625, 1537, 1429,
1384, 1211, 1117 cm-1; ESI-MS: m/z 333.0 [M+1]+; HRMS: m/z
339.1106 calcd for C20H13F3N2 + H+ (339.1104).
85 ESI.
Recyclability of Cu-Mn catalyst B: The recyclability of Cu-Mn
B catalyst was checked using a model reaction between 2-
aminopyridine (2a), benzaldehyde (3a) and phenylacetylene (4a).
The mixture of 2a (100 mg, 1 mmol) and 3a (113 mg, 1 mmol)
90 was stirred for 15 min. Water (3 mL) was added followed by
addition of 4a (163 mg, 1.5 mmol). Then, Cu-Mn catalyst (10
mg, 10 mol%) was added, and resulting mixture was refluxed at
100 °C for 4 h. The reaction mixture was filtered through
Whatman filter paper followed by washing with 3 x 25 mL water.
95 Recovered catalyst was dried in oven and reused in next cycle.
The catalyst was recycled 4 times and the amount of catalyst
recovered and percentage yield of the 5a was determined.
25 3-Benzyl-6-fluoro-2-(furan-2-yl)-imidazo[1,2-a]pyridine (5t):
1
Yellow crystalline solid; m.p. 166-167 °C; H NMR (CDCl3, 400
MHz): δ 7.70-7.68 (m, 1H), 7.65-7.63 (m, 1H), 7.54 (s, 1H),
7.34-7.28 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 7.10 (t, J = 8.0 Hz,
1H), 6.96 (s, 1H), 6.56 (s, 1H), 4.62 (s, 2H); 13C NMR (CDCl3,
1
30 125 MHz): δ 153.3 (d, JCF = 223.9 Hz), 142.7, 142.2, 136.0,
129.1, 128.0, 127.1, 119.6, 117.5, 117.4, 117.3, 117.0, 111.7,
2
110.3 (d, JCF = 49.0 Hz), 108.6, 30.1; 19F NMR (376.50 MHz,
CDCl3): δ -138.95 (s, 1F); IR (CHCl3): νmax 3400, 2922, 2852,
1650, 1537, 1453, 1384, 1219, 1020 cm-1; ESI-MS: m/z 293.0
35 [M+1]+; HRMS: m/z 293.1084 calcd for C18H13FN2O + H+
(293.1085).
Cell culture and cell proliferation assay. Human promyelocytic
leukemia cell lines HL-60, human pancreatic cancer cell line
100 MIAPaCa-2 and human prostate cancer cell line PC-3 were
purchased from Sigma Aldrich, India (ECACC, type). HL-60 and
PC-3 cells were grown in RPMI growth medium whereas
MIAPaCa-2 and A549 cells were grown in MEM medium
containing 10% FCS, 100U penicillin and 100 mg streptomycin
105 per mL medium. Cells were grown in CO2 incubator (Thermocon
Electron Corporation, Houston, TX) at 37 ºC with 95% humidity
and 5% CO2 gas environment. Cells treated with tested materials
were dissolved in DMSO while the untreated control cultures
received only the vehicle (DMSO < 0.2%). Cells were seeded in
110 96 well plates and exposed to tested compounds at 10, 30 and 100
µM concentrations for 48 h time interval. MTT dye (2.5 mg/ml in
PBS) was added 4 hrs priors to experiment termination. The
plates were then centrifuged at 1500 rpm for 15 min and the
supernatant was discarded, while the MTT formazan crystals
115 were dissolved in 150 µl of DMSO. The OD was measured at 570
nm with reference wavelength of 620 nm and the % growth
inhibition was determined.10
3-Benzyl-2-(3,5-difluorophenyl)-8-methyl-imidazo[1,2-
a]pyridine (5u): Yellow crystalline solid; m.p. 164-165 °C; H
1
NMR (CDCl3, 400 MHz): δ 7.54 (d, J = 8.0 Hz, 1H), 7.28-7.18
40 (m, 5H), 7.04 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 1H), 6.74-
6.68 (m, 1H), 6.60 (t, J = 8.0 Hz, 1H), 4.31 (s, 2H), 2.62 (s, 3H);
1
13C NMR (CDCl3, 100 MHz): δ 163.1 (d, JCF = 222.3 Hz),
144.9, 136.2, 128.5, 127.7, 127.5, 126.8, 121.3, 119.1, 113.2,
2
2
111.1 (d, JCF = 31.4 Hz), 103.2 (d, JCF = 26.0 Hz), 29.50, 16.7;
45 19F NMR (376.50 MHz, CDCl3): δ -109.65 (t, J = 3.8 Hz, 2F); IR
(CHCl3): νmax 3396, 2921, 2851, 1738, 1624, 1348, 1155, 1021
cm-1; ESI-MS: m/z 335.0 [M+1]+; HRMS: m/z 335.1354 calcd for
C21H16F2N2 + H+ (335.1354).
3-Benzyl-2-(furan-2-yl)-8-methyl-imidazo[1,2-a]pyridine (5v):
1
50 Brown crystalline solid; m.p. 131-132 °C; H NMR (CDCl3, 400
MHz): δ 7.55 (d, J = 4.0 Hz, 1H), 7.44 (s, 1H), 7.21-7.09 (m,
5H), 6.90 (d, J = 8.0 Hz, 1H), 6.80 (brs, 1H), 6.55 (t, J = 8.0 Hz,
1H), 6.44 (d, J = 4.0 Hz, 1H), 4.51 (s, 2H), 2.63 (s, 3H); 13C
NMR (CDCl3, 125 MHz): δ 142.5, 136.8, 128.9, 127.7, 127.2,
55 126.8, 121.2, 121.0, 118.5, 112.6, 111.0, 29.7, 17.4 (one C signal
not observed); IR (CHCl3): νmax 3400, 2921, 2851, 1738, 1630,
1578, 1453, 1384, 1020 cm-1; ESI-MS: m/z 289.0 [M+1]+;
HRMS: m/z 289.1336 calcd for C19H16N2O + H+ (289.1335).
Acknowledgements
Authors are thankful to analytical department, IIIM for NMR,
120 MS and IR analysis of our compounds.
3-Benzyl-2-(2-chlorophenyl)-8-methyl-imidazo[1,2-a]pyridine
1
60 (5w): Cream colored solid; m.p. 162-163 °C; H NMR (CDCl3,
Notes and references
400 MHz): δ 7.52 (d, J = 8.0 Hz, 2H), 7.41 (t, J = 4.0 Hz, 1H),
7.18-7.11 (m, 5H), 7.00 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 4.0 Hz,
6
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DOI: 10.1039/C3RA42046A
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