Metal-free benzoylation of imidazoheterocycles by oxidative decarboxylation of arylglyoxylic acids

Article abstract of DOI:10.1039/d0ob01842b

A simple and straightforward approach has been realized for the direct benzoylation of imidazoheterocycles by oxidative decarboxylation of arylglyoxylic acids in the presence of K2S2O8 as an oxidant. Various functional groups were tolerated on both imidazoheterocycles and arylglyoxylic acids and a wide range of C5-benzoyl-imidazoheterocycles were obtained in good to high yields (50-84%). Radical trapping experiments confirmed the involvement of the radical pathway. The developed protocol is amenable for a scale-up reaction. This journal is

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DOI: 10.1039/D0OB01842B
ARTICLE
Metal-Free Benzoylation of Imidazoheterocycles by Oxidative
Decarboxylation of Arylglyoxylic Acids
Received 00th January 20xx,
Accepted 00th January 20xx
Sonam Jaspal,a Vikki N. Shinde,a Neha Meena,a Dhananjay S, Nipate,a Krishnan Rangan,b and Anil
Kumara,*
DOI: 10.1039/x0xx00000x
A simple and straightforward approach has been realized for the direct benzoylation of imidazoheterocycles by oxidative
decarboxylation of arylglyoxylic acids in the presence of K2S2O8 as oxidant. Various functional groups were tolerated both
on imidazoheterocycles as well as on arylglyoxylic acids and a wide range of C5-benzoyl-imidazoheterocycles were
obtained in good to high yields (50-84%). Radical trapping experiments confirmed involvement of the radical pathway. The
developed
protocol
is
amenable
for
a
scale-up
reaction.
developed an efficient method for the direct acylation of 2H-
indazoles using α-oxocarboxylic acids under silver-catalyzed
decarboxylative oxidative coupling reaction.15 Lu and co-
workers developed a cobalt-catalyzed decarboxylative method
for the benzoylation of oxazoles and thiazoles using α-
oxocarboxylic acids.16 Muthusubramanian et al. described a
silver catalyzed acylation of pyridine-N-oxides by α-
oxocarboxylic acid.17 α-Oxocarboxylic acids have been also
used as acyl radical source in oxidative radical addition-
cyclization cascade reaction for the construction of carbonyl-
containing heterocycles.18 Despite these significant advances
in acylation of several heteroarenes, Minisci type acylations
under metal-free conditions remain underdeveloped.
Introduction
Direct formation of carbon-carbon (C-C) bond by C-H bond
functionalization is a powerful approach for the synthesis of
compounds with extensive applications in drug discovery and
materials.1 Various strategies have been developed for the
direct C-H bond functionalization using transition metal
catalysis,2 organocatalysis,3 radical cross-coupling and
photocatalysis,4 electrocatalysis,5 and enzyme catalysis.6
Among them, addition of a carbon-centered radical to an
electron-deficient N-heteroaromatic base, known as the
Minisci reaction, has seen an upsurge in interest in the
chemical community for the development of C–C bond
forming reactions in recent years.7 Since the Minisci and co-
workers’ pioneering work on use of α-oxocarboxylic acids in
the decarboxylative acylation of N-heteroarenes,8 several
efficient protocols have been developed for the synthesis of
acylated heteroarenes using α-oxocarboxylic acids as green
acyl transfer agents (Scheme 1).9 For example, Yotphan et al.
Previous work
X
X
R
O
R
N
N
N
R1
H
O
R
N
X = CH, N
N
N
R1
Ref 13
Ref 15
O
N
Ref 11
R1
N
N
O
O
H
N
R1
N
R2
O
N
N
N
O
R
developed
a
Cu(OAc)2/K2S2O8-mediated acylation of
R
COOH
+
R2
Ref 14
X
R
Ref 10
O
pyrazolones.10 Laha and co-workers developed regioselective
monoacylation of (NH)-free pyrroles under silver-free Minisci
reaction conditions.11 Earlier, they reported an intramolecular
Minisci-type acylation using α-oxocarboxylic acids for the
synthesis of azafluorenones and fluorenones under silver-free
N
K2S2O8 or
R
X
(NH4)2S2O8
R
O
N
O
N
X
N
O
X = NH, S, O
Ref 16
O
Ref 17
N
N
N
N
Radical initiator
Radical initiator
N
N
RX
RX
Ref. 22
Ref. 21
R
conditions.12 Lee and co-workers reported
a
metal-,
R
C3-functionalization
C5-functionalization
photocatalyst-, and light-free acylation of quinolines and other
heterocycles.13 Prabhu et al. developed acylation of electron-
deficient heteroaromatic compounds using α-oxocarboxylic
acids as acyl source under photoredox conditions.14 Oh et al.
This work
R1
X
R1
X
O
N
N
K2S2O8 (3 equiv.)
+
N
N
Ar
COOH
DMSO/H2O, 60 oC, 3 h
X = CH, N
O
Ar
Scheme 1 Acylation of heteroarenes using α-oxocarboxylic acids as acyl source and
functionalization of imidazoheterocycles
a. Department of Chemistry, Birla Institute of Technology and Science Pilani, Pilani
Campus, Rajasthan, 333031, India
On the other hand, imidazo[1,2-a]pyridine derivatives exhibit a
wide range of biological activities.19 This scaffold is found in
many commercially available drugs such as Alpidem, Zolpidem,
b. Department of Chemistry, Birla Institute of Technology and Science Pilani,
Hyderabad Campus, Telangana, 500078, India.
Electronic Supplementary Information (ESI) available: [copy of 1H and 13C NMR for
3, 4, 5 & 8 and single crystal X-ray data for 3aa]. See DOI: 10.1039/x0xx00000x
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ARTICLE
Journal Name
Zolimidine, Olprinone, Soraprazan and compounds in reaction (Table 1, entries 14-16). Reaction did VnieowtArwticolerOknlianet
DOI: 10.1039/D0OB01842B
biological testing and preclinical evaluation. Therefore, room temperature and 3aa was obtained in 12% and 53% yield
synthesis and functionalization of imidazoheterocycles has when model reaction was performed at 40 C and 100 C,
gained significant attention of chemists during the past respectively (Table 1, entries 17-19). Yield of 3aa did not
decades.20 Among different approaches, direct C-H bond increase on prolonging reaction time to 24 h (Table 1, entry
functionalization of imidazo[1,2-a]pyridines using various 20). Thus, 2a (3.0 equiv.), K2S2O8 (3.0 equiv.), DMSO/H2O (3
reagents through radical pathway has emerged as promising mL, 4:1 v/v) at 60 C for 3 h were selected as optimum
area in organic synthesis.21 The protocols developed for the reaction conditions for this reaction (Table 1, entry 12).
radical functionalization of imidazo[1,2-a]pyridines mostly deal
with functionalization at C3-position and only a few reports
are available for functionalization at C5-position22 (Scheme 1).
Herein, we report a C5-benzoylation of imidazoheterocycles by
oxidative decarboxylation of arylglyoxylic acids under metal-
free conditions (Scheme 1).
Table 1. Optimization of reaction conditions for 3aa.a
O
N
Ph
O
N
N
Oxidant,
Solvent
N
Ph
+
OH
Ph
N
+
Ph
Ph
N
O
Temp., Time
O
Ph
Ph
4aa
1a
3aa
O
2a
Entry
Oxidant
Solvent
% Yieldb
3aa
29
49
4aa
10
15
<10
-
Results and discussion
1
2
3
4
5
6
7
8
9
10
11
12d
13e
14d,f
15d,g
16d,h
17d,i
18d,j
19d,k
20d,l
Na2S2O8
K2S2O8
(NH4)2S2O8
TBHP
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
DMA
Toluene
CH3CN
H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
DMSO/H2O
An initial reaction of 2-phenylimidazo[1,2-a]pyridine (1a, 0.2
mmol) and phenylglyoxylic acid (2a, 0.5 mmol) in the presence
of Na2S2O8 (3.0 equiv.) at 60 C after 3 h afforded 5-benzoyl-2-
phenylimidazo[1,2-a]pyridine (3aa) and (2-phenylimidazo[1,2-
a]pyridine-5,8-diyl)bis(phenylmethanone) (4aa) in 29% and
10%, respectively. Structure of 3aa and 4aa were confirmed by
IR, 1H and 13C{1H} NMR, and HRMS analysis. Further, the
structure of 3aa was unambiguously confirmed by single-
crystal X-ray diffraction study (Figure 1, CCDC No. 1978834).
20
c
-
c
PIDA
-
-
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
47
45
18
15
-
c
-
c
-
-
21
56
62
61
26
29
29
<10
14
12
17
<10
<10
<10
-
O
N
c
-
N
3aa
12
53
60
-
17
18
CCDC No. 1978834
Figure 1 The ORTEP crystal structure diagram of 3aa. The thermal ellipsoids are
drawn at the 50% probability level.
aReaction conditions: 1a (0.2 mmol), 2a (0.5 mmol), K2S2O8 (3.0 equiv.), solvent (3
mL), 60 C, 3 h. bIsolated yield. cNo reaction, 2a (0.6 mmol) was used. 2a (0.8
d
e
mmol) was used. AgNO3 (1.5 equiv.) was used as additive; gTFA (1.5 equiv.) was
f
After confirming the structure of 3aa, a series of experiments
were performed to optimize the reaction conditions for
decarboxylative benzoylation of 1a using 2a as benzoyl source
(Table 1). On changing the oxidant to K2S2O8 the yield of 3aa
increased to 49% whereas, the use of (NH4)2S2O8 was found to
be less effective for this protocol (Table 1, entries 2-3).
Oxidants like TBHP (tert-butyl hydroperoxide) and IBD
(iodobenzene diacetate) were also found to be ineffective for
this reaction (Table 1, entries 4-5). Screening of different
solvents viz. DMSO, DMF, DMA, CH3CN, toluene and H2O
reveled that polar aprotic solvents such as DMSO, DMF and
DMA were more suitable medium for this reaction (Table 1,
entries 6-10). Interestingly, yield of 3aa improved to 56% when
mixture of DMSO and H2O (3:1, v/v) was used as the reaction
medium (Table 1, entry 11). Yield of 3aa increased to 62% on
increasing the amount of 2a (0.6 mmol, 3 equiv.) but no
increment in the yield of 3aa was observed on further
increasing the amount of 2a (Table 1, entries 12-13).
Detrimental effect on the yield of 3aa was observed when
additives such as AgNO3, TFA and DIPEA were used in the
used as additive; hDIPEA (1.5 equiv.) was used as additive; Reaction at room
i
temperature. jReaction at 40 C. kReaction at 100 C. lReaction time 24 h.
With the optimized reaction conditions in hand, we
investigated the scope of imidazo[1,2-a]pyridines (Table 2). A
wide range of 2-arylimidazo[1,2-a]pyridines with both
electron-donating and electron-withdrawing substituents such
as Me, OMe, CF3, CN and halogens on C2-benzene ring (1a-g)
on reaction with 2a afforded the corresponding benzoylated
products (3aa-ga) with good yields. 2-(Thiophen-2-
yl)imidazo[1,2-a]pyridine (1h) also successfully afforded the
desired benzoylated products (3ha) in 50% yield. Similarly,
reaction of 2-arylimidazo[1,2-a]pyridines substituted with
methyl and bromo groups at different positions on the
pyridine ring (1i-n) afforded the corresponding benzoyl
derivatives (3ia-na) in good yields (63-83%). It was found that
the imidazo[1,2-a]pyridines with methyl substituent on
pyridine ring at C6- and C8-position provided higher yields as
compared to unsubstituted imidazo[1,2-a]pyridines. C3-
substituted
substrate,
3-methyl-2-phenylimidazo[1,2-
2 | J. Name., 2012, 00, 1-3
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Journal Name
ARTICLE
a]pyridine (1o) also reacted under these condition to give the To verify the efficiency of designed protocol, thVeiewgrAartmicle-sOcnalinlee
DOI: 10.1039/D0OB01842B
corresponding C5-benzoyl derivative (3oa) in 68% yield. synthesis of 3aa was carried out by the reaction of 1a (5 mmol)
Interestingly, reaction of imidazo[1,2-a]pyrimidines (1p-s) with with 2a (15 mmol) under the standard reaction conditions
substituents such as methyl, methoxy and chloro on C2- (Scheme 2a). To our expectation, the desired C5-benzoylated
benzene ring with 2a provided the corresponding C5-benzoyl product 3aa was isolated in 63% yield without significant
derivatives 3pa-sa in high yields (76-85%). The regioselectivity change in the efficacy of the reaction. Further, synthetic
for C5-benzoyl of imidazo[1,2-a]pyrimidines was confirmed by application of the method was demonstrated by reducing 3aa
NOE experiment (see ESI). Higher yield in case of imidazo[1,2- to phenyl(2-phenylimidazo[1,2-a]pyridin-5-yl)methanol (8) in
a]pyrimidines as compared to imidazo[1,2-a]pyridines may be 90% yield using sodium borohydride in methanol (Scheme 2b)
due to the extra stability of the radical intermediate by the
N
Ph
O
N
Standard conditions
N
nitrogen atom of the pyrimidine ring and/or more electron
deficient pyrimidine ring. Finally, substrate scope of
arylglyoxylic acids was examined. Reaction of 1a with a variety
of substituted arylglyoxylic acids (2b-e) afforded the
corresponding benzoylated products (3ab-ae) in good yields
(67-76%). Heteroarylglyoxylic acids viz. 3-indoleglyoxylic acid
(2f) and 2-thiopheneglyoxylic acid (2g) also reacted
successfully under these conditions to afford the
corresponding products 3af and 3ag in 78% and 55% yields,
respectively. Finally, benzoylation of a commercial drug
molecule, Zolimidine was performed under optimized
condition to give the corresponding C5-benzoylated derivative
3ta in 51% yield.
+
Ph
a)
N
Ph
COOH
(15 mmol)
NaBH4 (1.5 equiv.)/MeOH
O
Ph
1a
3aa
(5 mmol)
, 63% (0.94 g)
2a
N
N
N
Ph
Ph
b)
N
3aa
8
, 90%
O
Ph
HO
Ph
Scheme 2 a) Gram scale synthesis of 3aa, b) Reduction of 3aa using NaBH4.
To gain insights into the benzoylation reaction mechanism, a
few control experiments were performed (Scheme 3). The
model reaction of 1a with 2a failed to produce desired product
3aa in the presence of a radical scavenger TEMPO (2,2,6,6-
tetramethylpiperidine-1-oxy),
but
2,2,6,6-
tetramethylpiperidin-1-yl benzoate (5) was isolated (Scheme
3a). Similarly, reaction of 1a with 2a in the presence of BHT
(butylated hydroxytoluene) under standard reaction
conditions also failed to produce the desired product 3aa
(Scheme 3b). Formation of 2,6-diisopropyl-4-methylphenyl
benzoate (6) was detected in HRMS analysis of the reaction
mixture. Further, heating 2a under optimal reaction conditions
produced benzaldehyde (7) in 56% yield (Scheme 3c). The
results from these control experiments suggested that the
benzoyl radical may be formed through the decarboxylative
reaction of phenylglyoxalic acid. Reaction of 5-methyl-2-
phenylimidazo[1,2-a]pyridine (1t) with 2a under standard
reaction conditions failed to produce any product and 1t was
recovered in 80% yield (Scheme 3d). Finally, competitive
experiment between 2-arylimidazo[1,2-a]pyridines, 1c and 1e
produced the corresponding products 3ca and 3ea in 2: 1 ratio
(Scheme 3e, see ESI), indicated that the substrate with
electron donating substituents on C2-benzene ring of imidazo-
heterocycle are more favorable for this reaction.
Table 2 Substrate scope for benzoylation of imidazoheterocycles.a,b,c
R2
X
N
R2
X
O
N
K2S2O8, 60 °C, 3h
R1
R1
+
N
N
Ar
COOH
2a-g
DMSO: H2O (3 mL, 4:1)
1a-s
3aa-ag
O
Ar
N
N
N
N
N
OMe
CN
Me
N
N
N
O
Ph
O
Ph
O
Ph
O
F
Ph
3aa
3ba
, 71%
3c
3da
, 62%
, 62%
a, 69%
N
N
N
N
Br
N
S
N
N
N
MeO
O
Me
Ph
O
Ph
O
Ph
O
Ph
3ea
, 56%
3fa
, 60%
3ga
, 70%
3ha
, 50%
N
N
N
N
N
OMe
Me
Me
N
N
N
N
Me
Me
O
Ph
O
Ph
O
Ph
O
Ph
3ka
, 77%
3la
, 83%
3ia
, 70%
3ja
,76%
Me
Br
N
N
N
N
N
Cl
N
N
N
N
Me
3oa
O
O
Ph
O
Ph
O
Ph
3ma
3na
O
Ph
N
, 75%
, 63%
, 68%
3pa
, 84%
N
N
N
N
N
N
N
Me
Cl
OMe
N
N
N
O
3ab
, 72%
OMe
Ph
3qa
, 85%
O
O
Ph 3sa
, 76%
O
Ph
3ra
, 81%
O
N
O
N
Standard conditions
TEMPO (5 equiv.)
Ph
+
+
Ph
Ph
a)
N
N
N
Ph
COOH
N
O
N
N
N
N
1a
2a
N
N
3aa
, 0%
5
(45 mg)
O
O
Ph
O
OMe
OMe
NH
iPr
O
N
O
MeO
N
O
O
Me
Standard conditions
BHT (5 equiv.)
O
Ph
Ph
+
b)
N
+
N
1a
O
F
Ph
COOH
Ph
OMe
2a
iPr
3ad
, 75%
3ac
, 76%
3af
, 78%
3ae
, 67%
Ph 3aa
, 0%
6
Standard conditions
N
Detected in HRMS
N
c)
d)
PhCHO
Ph
COOH
SO2Me
N
N
7
, 57%
2a
O
N
O
O
Ph
Standard conditions
3ag
, 55%
3ta
, 51%
No reaction
recovered 80%
Ph
S
+
N
1t
Ph
COOH
2a
Me
1t
aReaction conditions: 1 (0.5 mmol), 2 (1.5 mmol), K2S2O8 (3 equiv.), DMSO: H2O
(3.0 mL, 4: 1 v/v), 60 °C, 3 h. bIsolated yields. cIn most of the cases C-3
benzoylated derivative (4) was formed in small amount (5-10%) which was not
isolated.
N
O
R
N
Standard conditions
N
+
R
e)
Ph
COOH
N
2a
O
Ph
1c
1e
, R = OCH3
, R = F
3ca: 3ea
= 2: 1
Scheme 3 Control experiments
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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ARTICLE
Based on the control experiments and literature reports,23
Journal Name
a
(quartet), m (multiplet), etc. HRMS (ESI) were reVcioewrdAertidcleuOsnilninge
DOI: 10.1039/D0OB01842B
plausible mechanistic pathway is depicted in Scheme 4. First, Q-TOF LC/MS spectrometer.
the thermal decomposition of K2S2O8 generated sulfate radical
(SO4•−).24 Next, the oxidative decarboxylation of 2a in the
•−
presence of SO4 generated benzoyl radical (A), which then
Experimental procedure for benzoylation
reacted regioselectively at the C5-position of 1a to afford the
radical intermediate B. Finally, the hydrogen radical
abstraction (HRA) by SO4•− or persulfate mediated single-
electron transfer (SET) followed by deprotonation produced
the desired product 3aa.
To a solution of 1 (0.5 mmol) in DMSO: H2O (3 mL, 4:1 v/v) was
added arylglyoxylic acid (3.0 equiv.) and K2S2O8 (3.0 equiv.) at
room temperature and the reaction mixture was stirred at 60
°C for 3 h. After completion of the reaction monitored by TLC,
the reaction mixture was allowed to attain room temperature.
The reaction mixture was poured into water (20 mL) and
extracted with ethyl acetate (3 × 15 mL). The combined
organic layer was dried over anhydrous Na2SO4 and
evaporated under vacuum. The resulting crude oil was purified
by column chromatography (silica gel 100-200 mesh) using n-
hexane/EtOAc as an eluent to afford 3.
2-
S2O8
2SO4
-
SO4
HSO4
N
N
O
O
Ph
Ph
SO4
1a
OH
N
N
Ph
2a
Ph
-
HRA
-CO2, -HSO4
O
3aa
B
O
Ph
A
O
Ph
Scheme 4 Proposed reaction mechanism
Phenyl(2-phenylimidazo[1,2-a]pyridin-5-yl)methanone (3aa)
Conclusions
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 96 mg
(62%); mp = 163-165 °C; FT-IR (neat): 2918, 2241, 1716, 1638,
1254, 756 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.24 (s, 1H), 8.09 –
8.07 (m, 2H), 7.98 (d, J = 8.8 Hz, 1H), 7.87 – 7.85 (m, 2H), 7.71 –
7.67 (m, 1H), 7.58 (t, J = 7.7 Hz, 2H), 7.50 (t, J = 7.7 Hz, 2H),
7.41 – 7.37 (m, 2H), 7.30 – 7.26 (m, 1H); 13C{1H} NMR (100
MHz, CDCl3): 190.4, 147.5, 146.3, 137.6, 133.5, 132.8, 131.7,
129.7, 128.8, 128.6, 128.3, 126.3, 122.5, 122.4, 122.2, 111.0;
HRMS (ESI) calcd for C20H15N2O+ [M + H]+ 299.1179, found
299.1174.
In summary, we have developed a metal- and photocatalyst-
free K2S2O8-mediated reaction for regioselective benzoylation
of imidazoheterocycles using arylglyoxylic acids as benzoyl
source. The reaction produced good yields and tolerated a
wide range of functional groups both on imidazoheterocycles
as well as on arylglyoxylic acids. Control experiments indicated
that the reaction was likely to proceed via a radical pathway.
The developed protocol is amenable for a scale-up reaction.
Given the high pharmaceutical importance of imidazo[1,2-
a]pyridines, the newly developed method will be useful for the
synthesis of variety of 5-aroylimidazo[1,2-a]pyridines under
metal-free and mild reaction conditions.
Phenyl(2-(p-tolyl)imidazo[1,2-a]pyridin-5-yl)methanone (3ba)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 105.5 mg
(71%); mp = 164-166 °C; FT-IR (neat) 2970, 2235, 1712, 1641,
1240, 764 cm-1; H NMR (400 MHz, CDCl3) δ 9.21 (s, 1H), 7.98
1
Experimental section
General information
– 7.95 (m, 3H), 7.86 – 7.84 (m, 2H), 7.71 – 7.66 (m, 1H), 7.57 (t,
J = 7.6 Hz, 2H), 7.39 (dd, J = 7.2, 1.2 Hz, 1H), 7.31 (d, J = 8.0 Hz,
2H), 7.26 (dd, J = 8.8, 7.2 Hz, 1H), 2.43 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): 190.4, 147.7, 146.3, 138.2, 137.6, 132.8,
131.6, 130.7, 129.7, 129.5, 128.6, 126.2, 122.4, 122.3, 122.0,
110.7, 21.4; HRMS (ESI) calcd for C21H17N2O+ [M + H]+
313.1335, found 313.1331.
All the chemicals were obtained from the commercial suppliers
and used without further purification. Arylglyoxalic acids were
synthesized by oxidation of corresponding aryl methyl ketones
using selenium dioxide following the reported procedure.25
Zolimidine was synthesized by reacting 2-(4-bromophenyl)-
imidazo[1,2-a]pyridine with sodium methane sulfonate in the
presence of CuI/L-proline.26 Reactions were monitored by
using thin-layer chromatography (TLC) on 0.2 mm silica gel
F254 plates. Column chromatography was performed over
silica gel (100-200 mesh) using n-hexane/EtOAc as an eluent.
Melting points were determined in open capillary tubes on an
automated melting point apparatus and are uncorrected. IR
spectra were recorded using an FT-IR spectrophotometer, and
(2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-5-yl)(phenyl)-
methanone (3ca)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 101 mg
(69%); mp = 181-183 °C; FT-IR (neat) 2848, 2254, 1720, 1641,
1521, 1284, 727 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.17 (s, 1H),
8.01 (d, J = 8.3 Hz, 2H), 7.95 (d, J = 8.9 Hz, 1H), 7.85 (d, J = 7.6
Hz, 2H), 7.68 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.7 Hz, 2H), 7.38 (d, J
= 7.2 Hz, 1H), 7.27 – 7.23 (m, 1H), 7.03 (d, J = 8.3 Hz, 2H), 3.90
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): 190.4, 159.9, 147.6,
146.3, 137.7, 132.8, 131.5, 129.7, 128.6, 127.6, 126.2, 122.3,
122.2, 121.9, 114.3, 110.2, 55.4; HRMS (ESI) calcd for
C21H17N2O2+ [M + H]+ 329.1285, found 329.1279.
values are reported in cm−1. The H and 13C{1H} NMR spectra
1
were recorded on 400 MHz and 100 MHz instruments,
respectively, with CDCl3 (TMS as an internal standard) or
DMSO-d6 as the solvent. Chemical shifts (δ) and coupling
constants (J) are reported in parts per million (ppm) and hertz,
respectively. Peak multiplicities of 1H-NMR signals were
designated as s (singlet), d (doublet), dd (doublet of doublet),
dt (doublet of triplet), td (triplet of doublet), t (triplet), q
4-(5-Benzoylimidazo[1,2-a]pyridin-2-yl)benzonitrile (3da)
4 | J. Name., 2012, 00, 1-3
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Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 91 mg 7.91 (m, 2H), 7.85 (d, J = 7.6 Hz, 2H), 7.69 (t, J = 7.8 Hz, 1H),
View Article Online
(62%); mp = 173-175 °C; FT-IR (neat) 3026, 2222, 1694, 1647, 7.65 (d, J = 5.2 Hz, 1H), 7.58 (t, J = 7.6 HDz,O2I:H10),.170.3495/D–0O7B.40318(4m2B,
1
1263, 761 cm-1; H NMR (400 MHz, CDCl3) δ 9.31 (s, 1H), 8.18 1H), 7.40 (d, J = 7.2 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H); 13C{1H}
(d, J = 8.0 Hz, 2H), 7.97 (d, J = 8.8 Hz, 1H), 7.86 (d, J = 7.6 Hz, NMR (100 MHz, CDCl3): 190.4, 146.2, 143.8, 137.6, 135.5,
2H), 7.77 (d, J = 7.7 Hz, 2H), 7.70 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 132.8, 131.6, 129.7, 128.6, 126.2, 126.1, 122.4, 122.3, 122.2,
7.6 Hz, 2H), 7.44 (d, J = 7.0 Hz, 1H), 7.35 – 7.31 (m, 1H); 13C{1H} 122.0, 111.0; HRMS (ESI) calcd for C18H13N2OS+ [M + H]+
NMR (100 MHz, CDCl3): 190.1, 146.1, 144.3, 137.2, 137.1, 305.0743, found 305.0738.
133.3, 132.7, 132.0, 129.8, 128.8, 126.8, 124.0, 122.9, 122.4,
(6-Methyl-2-phenylimidazo[1,2-a]pyridin-5-yl)(phenyl)methanone
(3ia)
118.9, 112.2, 111.8; HRMS (ESI) calcd for C21H14N3O+ [M + H]+
324.1131, found 324.1127.
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 104.5 mg
(70%); mp = 181-183 °C; FT-IR (neat) 2915, 2362, 1697, 1634,
1475, 1248, 725 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H),
(2-(4-Fluorophenyl)imidazo[1,2-a]pyridin-5-yl)(phenyl)methanone
(3ea)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 83 mg 8.05 (d, J = 8, 2H), 7.86 (d, J = 8, 2H), 7.74 (s, 1H), 7.70 (t, J = 7.6
(56%); mp = 171-173 °C; FT-IR (neat) 3010, 2328, 1695, 1631, Hz, 1H), 7.59 (t, J = 7.4 Hz, 2H), 7.48 (t, J = 7.4 Hz, 2H), 7.37 (t, J
1254, 754, 519, 418 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.19 (s, = 7.4 Hz, 1H), 7.20 (s, 1H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz,
1H), 8.05 (dd, J = 8.8, 5.6 Hz, 2H), 7.96 (d, J = 8.8 Hz, 1H), 7.86 CDCl3) 190.3, 146.9, 146.6, 138.0, 134.1, 133.9, 132.4, 130.0,
(d, J = 7.2 Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.58 (t, J = 7.6 Hz, 129.6, 128.7, 128.5, 128.1, 126.4, 123.2, 121.3, 111.5, 17.8.;
2H), 7.40 (d, J = 7.2 Hz, 1H), 7.30 – 7.26 (m, 1H), 7.18 (t, J = 8.6 HRMS (ESI) calcd for C21H17N2O+ [M + H]+ 313.1335, found
Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): 190.1, 163.2 (d, J = 313.1337.
248.7 Hz), 145.3, 144.8, 137.1, 133.2, 131.7, 129.8, 128.76 ,
128.3 (d, J = 8.3 Hz), 123.9, 122.8, 121.6, 116.1, 115.9, 110.6;
HRMS (ESI) calcd for C20H14FN2O+ [M + H]+ 317.1085, found
(6-Methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-5-yl)(phenyl)-
methanone (3ja)
317.1079.
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 112 mg
(76%); mp = 173-175 °C; FT-IR (neat) 3111, 2250, 1697, 1630,
1468, 1249, 725 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.08 (s, 1H),
7.95 (d, J = 8.4 Hz, 2H), 7.86 – 7.84 (m, 2H), 7.80 (s, 1H), 7.70 (t,
(2-(4-Bromophenyl)imidazo[1,2-a]pyridin-5-yl)(phenyl)methanone
(3fa)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 82.5 mg, J = 7.4 Hz, 1H), 7.58 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H),
(60%); mp = 176-178 °C; FT-IR (neat) 3018, 2246, 1693, 1642, 7.22 (d, J = 2.0 Hz, 1H), 2.46 (s, 3H), 2.42 (s, 3H); 13C{1H} NMR
1223, 738 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.22 (s, 1H), 7.97 – (100 MHz, CDCl3) 190.2, 146.3, 146.1, 138.4, 137.4, 133.8,
7.93 (m, 3H), 7.85 (dd, J = 8.2, 1.4 Hz, 2H), 7.71 – 7.67 (m, 1H), 133.0, 131.0, 130.0, 129.8, 129.6, 128.7, 126.2, 124.7, 120.6,
7.63 – 7.62 (m, 1H), 7.60 (t, J = 2.2 Hz, 2H), 7.58 – 7.56 (m, 109.8, 21.4, 21.1; HRMS (ESI) calcd for C22H20N2O+ [M + H]+
1H), 7.41 (dd, J = 7.2, 1.2 Hz, 1H), 7.31 – 7.27 (m, 1H); 13C{1H} 313.1335, found 313.1332.
NMR (100 MHz, CDCl3): 190.2, 146.0, 145.7, 137.3, 133.1,
132.0, 131.9, 131.7, 129.8, 128.7, 127.9, 123.1, 122.6, 122.6,
122.2, 111.0; HRMS (ESI) calcd for C20H14BrN2O+ [M + H]+
(2-(4-Methoxyphenyl)-6-methylimidazo[1,2-a]pyridin-5-yl)-
(phenyl)methanone (3ka)
377.0248, found 377.0250.
Eluent: n-hexane/EtOAc (8: 2 v/v); orange solid; yield: 110 mg
(77%); mp = 188-190 °C; FT-IR (neat) 2920, 2248, 1683, 1637,
1471, 1224, 745 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H),
7.98 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 6.8 Hz, 2H), 7.70 – 7.67 (m,
(2-(2-Methoxyphenyl)imidazo[1,2-a]pyridin-5-yl)(phenyl)-
methanone (3ga)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 102 mg 2H), 7.58 (t, J = 7.6 Hz, 2H), 7.18 (d, J = 1.2 Hz, 1H), 7.01 (d, J =
(70%); mp = 127-129 °C; FT-IR (neat) 2895, 2357, 1695, 1595, 8.4 Hz, 2H), 3.89 (s, 3H), 2.45 (s, 3H); 13C{1H} NMR (100 MHz,
1253, 725 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H), 8.57 CDCl3) 190.4, 159.8, 147.1, 146.7, 137.7, 132.8, 132.7, 130.9,
(d, J = 2.8 Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 7.2 Hz, 129.7, 128.6, 127.5, 126.5, 124.4, 120.9, 114.2, 109.4, 55.3,
+
2H), 7.69 (t, J = 7.6 Hz, 1H), 7.58 (t, J = 7.6 Hz, 2H), 7.46 – 7.43 21.0; HRMS (ESI) calcd for C22H19N2O2 [M + H]+ 343.1441,
(m, 1H), 7.38 – 7.36 (m, 1H), 7.29 – 7.25 (m, 2H), 6.92 (d, J = found 343.1440.
8.8 Hz, 1H), 4.02 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): 190.0,
156.1, 144.2, 137.2, 133.3, 132.2, 132.0, 131.6, 130.3, 129.9,
(8-Methyl-2-phenylimidazo[1,2-a]pyridin-5-yl)(phenyl)methanone
(3la)
128.9, 128.8, 123.9, 122.5, 121.6, 115.0, 113.6, 112.8, 55.9;
+
HRMS (ESI) calcd for C21H17N2O2 [M + H]+ 329.1285, found Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 124 mg
329.1288.
(83%); mp = 156-158 °C; FT-IR (neat) 2918, 2346, 1716, 1638,
1
1450, 1252, 764 cm-1; H NMR (400 MHz, CDCl3 δ 9.29 (s, 1H),
Phenyl(2-(thiophen-3-yl)imidazo[1,2-a]pyridin-5-yl)methanone
(3ha)
8.11 – 8.09 (m, 2H), 7.84 – 7.82 (m, 2H), 7.66 (t, J = 7.4 Hz, 1H),
7.56 (t, J = 7.4 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.37 (t, J = 7.4
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 75.5 mg Hz, 1H), 7.33 (d, J = 7.2 Hz, 1H), 7.06 (dd, J = 7.2, 0.8 Hz, 1H),
(50%); mp = 145-147 °C; FT-IR (neat) 2991, 2366, 1695, 1628, 2.83 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) 190.3, 146.9, 146.6,
1248, 733 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.12 (s, 1H), 7.95 – 138.1, 134.1, 133.9, 132.5, 130.0, 129.6, 128.7, 128.5, 128.1,
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Journal Name
126.4, 123.2, 121.3, 111.5, 17.8; HRMS (ESI) calcd for 8.67 (d, J = 3.2 Hz, 1H), 8.04 (d, J = 7.6 Hz, 2H), 7.91 (d, J = 8.0
View Article Online
C21H17N2O+ [M + H]+ 313.1335, found 313.1332.
Hz, 2H), 7.77 – 7.73 (m, 1H), 7.61 (t, J = 7.6 Hz, 2H), 7.32 – 7.28
(m, 2H), 7.22 – 7.21 (m, 1H), 2.43 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): 189.8, 150.0, 149.9, 147.2, 139.1, 136.3, 135.9,
134.0, 130.2, 129.9, 129.6, 129.0, 126.5, 112.9, 108.1, 21.4;
DOI: 10.1039/D0OB01842B
(2-(4-Chlorophenyl)-8-methylimidazo[1,2-a]pyridin-5-yl)(phenyl)-
methanone (3ma)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 125 mg HRMS (ESI) calcd for C20H16N3O+ [M + H]+ 314.1288, found
(75%); mp = 169-171 °C; FT-IR (neat) 2957, 2216, 1689, 1654, 314.1281.
1219, 731, 602, 547 cm-1; H NMR (400 MHz, CDCl3 δ 9.26 (s,
1H), 8.05 – 8.02 (m, 2H), 7.83 – 7.81 (m, 2H), 7.69 – 7.65 (m,
1H), 7.57 (t, J = 7.6 Hz, 2H), 7.47 – 7.44 (m, 2H), 7.34 (d, J = 7.6
Hz, 1H), 7.08 (dd, J = 7.2, 0.8 Hz, 1H), 2.81 (s, 3H); 13C{1H} NMR Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 117.5 mg
1
(2-(4-Methoxyphenyl)imidazo[1,2-a]pyrimidin-5-yl)(phenyl)-
methanone (3ra)
(100 MHz, CDCl3): 190.1, 146.2, 145.1, 137.8, 134.1, 133.9, (81%); mp = 159-162-142 °C; FT-IR (neat) 2932, 2356, 1697,
1
132.7, 131.7, 130.0, 129.7, 129.0, 128.6, 127.7, 123.4, 122.3, 1643, 1468, 1223, 762 cm-1; H NMR (400 MHz, CDCl3) δ 8.87
111.5, 17.9; HRMS (ESI) calcd for C21H16ClN2O+ [M + H]+ (s, 1H), 8.66 (d, J = 4.4 Hz, 1H), 8.09 (d, J = 8.0 Hz, 2H), 7.91 (d, J
347.0946, found 349.0946.
= 7.6 Hz, 2H), 7.75 (t, J = 7.6 Hz, 1H), 7.62 (t, J = 7.6 Hz, 2H),
7.21 (d, J = 4.4 Hz, 1H), 7.04 (d, J = 8.4 Hz, 2H), 3.90 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): 189.9, 160.5, 150.0, 149.8,
(7-Bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)(phenyl)methanone
(3na)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 86.5 mg 113.0, 107.6, 55.4; HRMS (ESI) calcd for C20H16N3O2 [M + H]+
(63%); mp = 189-191 °C; 1H NMR (400 MHz, CDCl3 δ 7.95 (dd, J 300.1131, found 300.1134.
= 8.4, 1.2 Hz, 2H), 7.89 (dd, J = 8.4, 1.2 Hz, 2H), 7.76 – 7.72 (m,
147.0, 136.1, 135.9, 134.0, 130.0, 129.0, 128.0, 125.6, 114.3,
+
(2-(4-Chlorophenyl)imidazo[1,2-a]pyrimidin-5-yl)(phenyl)-
methanone (3sa)
1H), 7.69 (dd, J = 9.6, 0.4 Hz, 1H), 7.65 (s, 1H), 7.59 – 7.55 (m,
2H), 7.44 – 7.39 (m, 3H), 7.36 – 7.32 (m, 1H); 13C{1H} NMR (100
MHz, CDCl3) 189.4, 147.2, 144.4, 135.5, 134.2, 132.8, 132.2, Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 110 mg
130.0, 129.5, 128.8, 128.5, 128.4, 126.2, 118.9, 108.0, 105.5; (76%); mp = 175-177 °C; FT-IR (neat) 3159, 2350, 1716, 1645,
1
HRMS (ESI) calcd for C20H14BrN2O+ [M + H]+ 377.0284, found 1226, 754, 662 cm-1; H NMR (400 MHz, CDCl3) δ 8.89 (s, 1H),
377.0279.
8.71 (d, J = 4.4 Hz, 1H), 8.08 – 8.06 (m, 2H), 7.92 – 7.90 (m, 2H),
7.78 – 7.74 (m, 1H), 7.62 (t, J = 7.6 Hz, 2H), 7.48– 7.45 (m, 2H),
7.23 (d, J = 4.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): 189.7,
150.0, 148.4, 147.8, 136.6, 135.8, 134.9, 134.2, 131.5, 130.0,
(3-Methyl-2-phenylimidazo[1,2-a]pyridin-5-yl)(phenyl)methanone
(3oa)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 102 mg 129.1, 129.0, 127.8, 113.1, 108.5; HRMS (ESI) calcd for
(68%); mp = 174-176 °C; FT-IR (neat) 2992, 2256, 1688, 1647, C19H13ClN3O+ [M + H]+ 334.0742, found 334.0737.
1
1458, 1249, 733 cm-1; H NMR (400 MHz, CDCl3) δ 8.04 (d, J =
(2-(4-(Methylsulfonyl)phenyl)imidazo[1,2-a]pyridin-5-yl)(phenyl)-
7.6 Hz, 2H), 7.92 (d, J = 8.8 Hz, 1H), 7.82 (d, J = 7.6 Hz, 2H), 7.72
methanone (3ta)
(t, J = 7.0 Hz, 1H), 7.58 (t, J = 7.6 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H),
7.40 (t, J = 7.2 Hz, 1H), 7.26 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 6.8 Eluent: n-Hexane/EtOAc (6: 4, v/v); yellow solid; yield: 70 mg
Hz, 1H), 2.33 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) 188.0, (51 %); mp = 217-219 °C; FT-IR (neat) 2768, 2309, 1725, 1641,
145.3, 145.2, 136.4, 134.3, 134.2, 130.6, 129.9, 129.0, 128.9, 1578, 1218, 772 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.32 (s, 1H),
128.5, 127.8, 121.6, 120.7, 119.4, 118.0, 14.4; HRMS (ESI) calcd 8.29 (d, J = 8.4 Hz, 2H), 8.08 (t, J = 8.2 Hz, 3H), 7.88 (d, J = 7.2
for C21H17N2O+ [M + H]+ 313.1335, found 313.1329.
Hz, 2H), 7.72 (t, J = 7.2 Hz, 1H), 7.60 (t, J = 7.4 Hz, 2H), 7.50 (d, J
= 6.8 Hz, 1H), 7.43 – 7.40 (m, 1H), 3.13 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 189.9, 140.3, 136.8, 133.5, 132.0, 130.3, 129.9,
Phenyl(2-phenylimidazo[1,2-a]pyrimidin-5-yl)methanone (3pa)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 130 mg 129.1, 128.9, 128.6, 128.2, 127.6, 127.2, 123.2, 122.0, 112.3,
(81%); mp = 190-192 °C; FT-IR (neat) 2850, 2302, 1695, 1664, 44.6; HRMS (ESI) calcd for C21H17N2O3S+ [M + H]+ 377.0954,
1
1263, 746 cm-1; H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H), 8.69 found 377.0932.
(d, J = 4.4 Hz, 1H), 8.14 (d, J = 6.8 Hz, 2H), 7.91 (d, J = 7.2 Hz,
2H), 7.75 (t, J = 7.4 Hz, 1H), 7.62 (t, J = 7.8 Hz, 2H), 7.50 (t, J =
7.4 Hz, 2H), 7.41 (t, J = 7.4 Hz, 1H), 7.22 (d, J = 4.4 Hz, 1H);
(4-Methoxyphenyl)(2-phenylimidazo[1,2-a]pyridin-5-yl)-
methanone (3ab):
13C{1H} NMR (100 MHz, CDCl3): 189.8, 150.0, 149.6, 147.5, Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 121 mg
136.5, 135.8, 134.1, 132.9, 130.0, 129.0, 128.8, 126.6, 113.1, (72%); mp = 153-155 °C; FT-IR (neat) 3156, 2243, 1717, 1647,
108.4; HRMS (ESI) calcd for C19H14N3O+ [M + H]+ 300.1131, 1464, 1251, 734 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.02 (s, 1H),
found 300.1129.
8.05 (d, J = 7.2 Hz, 2H), 7.91 (t, J = 8.4 Hz, 3H), 7.48 (t, J = 7.6
Hz, 2H), 7.38 (t, J = 7.4 Hz, 1H), 7.33 (d, J = 6.8 Hz, 1H), 7.25 (d,
J = 7.2 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 3.95 (s, 3H); 13C{1H}
Phenyl(2-(p-tolyl)imidazo[1,2-a]pyrimidin-5-yl)methanone (3qa)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 127.5 mg NMR (100 MHz, CDCl3): 189.0, 163.8, 147.1, 146.3, 133.6,
(85%); mp = 121-123 °C; FT-IR (neat) 3017, 2222, 1684, 1647, 132.4, 132.2, 129.8, 128.8, 128.2, 126.3, 122.3, 121.8, 120.7,
1484, 1282, 725 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.89 (s, 1H),
6 | J. Name., 2012, 00, 1-3
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+
114.0, 110.6, 55.6; HRMS (ESI) calcd for C21H17N2O2 [M + H]+ (2-Phenylimidazo[1,2-a]pyridin-5-yl)(thiophen-2-yl)methanone
View Article Online
DOI: 10.1039/D0OB01842B
329.1285, found 329.1297.
(3ag)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 86 mg
(55%); mp = 174-176 °C; FT-IR (neat) 3115, 2317, 1712, 1624,
1220, 733 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.0 (s, 1H), 8.04 (d,
J = 7.2 Hz, 2H), 7.97 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 4.4 Hz, 1H),
7.80 (d, J = 3.6 Hz, 1H), 7.60 (d, J = 6.8 Hz, 1H), 7.48 (t, J = 7.2
Hz, 2H), 7.39 – 7.36 (m, 1H), 7.31 (d, J = 8.8 Hz, 1H), 7.26 – 7.24
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3): 181.4, 147.1, 146.2,
142.7, 135.3, 134.9, 133.4, 131.9, 128.8, 128.3, 128.3, 126.3,
122.4, 122.1, 119.8, 110.5; HRMS (ESI) calcd for C18H13N2OS+
[M + H]+ 305.0743, found 305.0748.
(2-Methoxyphenyl)(2-phenylimidazo[1,2-a]pyridin-5-yl)-
methanone (3ac)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 128 mg
(76%); mp = 178-180 °C; FT-IR (neat) 2922, 2265, 1698, 1645,
1468, 1261, 746 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.52 (s, 1H),
8.13 – 8.10 (m, 2H), 8.03 (d, J = 8.8 Hz, 1H), 7.56 (td, J = 8.6, 1.6
Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.45 (dd, J = 7.6, 1.6 Hz, 1H),
7.40 (t, J = 7.4 Hz, 1H), 7.35 – 7.33 (m, 1H), 7.28 – 7.24 (m, 1H),
7.15 – 7.11 (m, 1H), 7.06 (d, J = 8.4 Hz, 1H), 3.78 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): 190.3, 157.3, 147.1, 146.0, 133.0,
132.6, 132.5, 129.5, 128.9, 128.5, 127.8, 126.4, 123.2, 122.9, (2-Phenylimidazo[1,2-a]pyridine-5,8-diyl)bis(phenylmethanone)
122.4, 120.7, 111.6, 111.4, 55.7; HRMS (ESI) calcd for (4aa)
C21H17N2O2+ [M + H]+ 329.1285, found 329.1278.
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 31 mg
(15%); mp = 175-177 °C; H NMR (400 MHz, CDCl3) δ 9.22 (s,
1H), 8.00 (dd, J = 8.2, 1.4 Hz, 2H), 7.96 (dd, J = 8.2, 1.4 Hz, 2H),
7.91 (dd, J = 8.2, 1.4 Hz, 2H), 7.74 – 7.70 (m, 1H), 7.68 – 7.64
1
(2-Phenylimidazo[1,2-a]pyridin-5-yl)(3,4,5-trimethoxyphenyl)-
methanone (3ad)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 150 mg
(m, 1H), 7.62 – 7.58 (m, 3H), 7.51 (d, J = 7.6 Hz, 2H), 7.44 (d, J =
(75%); mp = 140-142 °C; FT-IR (neat) 2849, 2220, 1688, 1658,
8.0 Hz, 2H), 7.41 – 7.39 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3):
1484, 1253, 758 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.05 (s, 1H),
193.1, 190.0, 148.4, 143.8, 137.2, 136.6, 133.8, 133.3, 133.2,
8.09 (d, J = 7.2 Hz, 3H), 7.51 (t, J = 7.6 Hz, 2H), 7.47 (d, J = 7.2
Hz, 1H), 7.43 – 7.39 (m, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.13 (s,
2H), 4.01 (s, 3H), 3.94 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3):
132.7, 132.4, 130.5, 129.9, 128.8, 128.6, 128.5, 128.4, 126.6,
+
122.4, 120.8, 110.9; HRMS (ESI) calcd for C27H19N2O2 [M + H]+
403.1441, found 403.1439.
188.9, 153.2, 143.0, 133.0, 131.9, 129.0, 129.0, 128.6, 128.0,
126.5, 123.8, 121.7, 121.4, 110.6, 107.9, 107.6, 61.1, 56.5; 2,2,6,6-Tetramethylpiperidin-1-yl benzoate (5):
+
HRMS (ESI) calcd for C23H21N2O4 [M + H]+ 389.1489, found
389.1486.
Eluent: n-hexane/EtOAc (8: 2 v/v); white solid; 45 mg; mp =
105-107 °C; H NMR (400 MHz, CDCl3) δ 8.14 – 8.11 (m, 1H),
1
8.10 – 8.09 (m, 1H), 7.62 – 7.58 (m, 1H), 7.51 – 7.47 (m, 2H),
(4-Fluorophenyl)(2-phenylimidazo[1,2-a]pyridin-5-yl)methanone
(3ae)
1.84 – 1.70 (m, 4H), 1.64 – 1.60 (m, 2H), 1.30 (s, 6H), 1.15 (s,
6H); 13C{1H} NMR (100 MHz, CDCl3): 166.4, 132.8, 129.6, 128.4,
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 108.5 mg
60.4, 39.1, 32.0, 20.9, 17.0; HRMS (ESI) calcd for C16H24NO2+ [M
(67%); mp = 171-173 °C; FT-IR (neat) 3217, 2217, 1695, 1614,
+ H]+ 262.1802, found 262.1807.
1
1246, 753, 542 cm-1; H NMR (400 MHz, CDCl3) δ 9.17 (s, 1H),
8.08 – 8.06 (dd, J = 8.8, 1.6 Hz, 2H), 7.97 (d, J = 8.8 Hz, 1H), Experimental procedure for the synthesis of compound 8.
7.93 – 7.90 (m, 2H), 7.50 (t, J = 7.7 Hz, 2H), 7.40 (d, J = 7.6Hz,
To a solution of 3aa (0.17 mmol; 1.0 equiv.) in methanol (10
mL) was added NaBH4 (0.25 mmol; 1.5 equiv.) portion-wise at
room temperature and the reaction was stirred at the same
temperature for 1 h. After completion of reaction monitored
by TLC, the solvent was evaporated under reduced pressure
and the resulting crude solid was washed with diethyl ether
1H), 7.36 (dd, J = 7.2, 1.6 Hz, 1H), 7.30 – 7.24 (m, 3H); 13C{1H}
NMR (100 MHz, CDCl3): 188.8, 147.5, 146.3, 133.7 (d, J = 3.3
Hz), 133.3, 132.4 (d, J = 9.1 Hz), 131.5, 128.8, 128.4, 126.3,
122.6, 122.2, 122.0, 116.1, 115.8, 110.9; HRMS (ESI) calcd for
C20H14FN2O+ [M + H]+ 317.1085, found 317.1087.
and n-pentane to get reduced compound 8 in 90% yield.
(1H-Indol-3-yl)(2-phenylimidazo[1,2-a]pyridin-5-yl)methanone
(3af)
Phenyl(2-phenylimidazo[1,2-a]pyridin-5-yl)methanol (8)
Eluent: n-hexane/EtOAc (8: 2 v/v); yellow solid; yield: 136 mg
Eluent: n-hexane/EtOAc (8: 2 v/v); white solid; yield: 45 mg
(78%); mp = 235-237 °C; FT-IR (neat) 3382, 3016, 2358, 1695,
(90%); mp = 96-98 °C; FT-IR (neat) 3325, 3061, 2816, 1637,
1
1644, 1334, 746 cm-1; H NMR (400 MHz, CDCl3) δ 8.80 (d, J =
1
1228, 735 cm-1; H NMR (400 MHz, CDCl3) δ 7.76 – 7.74 (m,
4.0 Hz, 1H), 8.46 – 8.44 (m, 1H), 8.01 – 7.99 (m, 2H), 7.84 –
7.80 (m, 2H), 7.51 (d, J = 6.8 Hz, 1H), 7.46 – 7.41 (m, 2H), 7.37 –
7.33 (m, 4H), 7.28 – 7.24 (m, 1H); 13C{1H} NMR (100 MHz,
3H), 7.34 – 7.32 (m, 8H), 6.95 (t, J = 8.0 Hz, 1H), 6.59 (d, J = 7.2
Hz, 1H), 5.97 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): 145.9,
144.7, 139.0, 138.8, 133.2, 128.8, 128.6, 128.4, 128.0, 126.8,
126.1, 124.8, 115.7, 111.6, 107.3, 72.6; HRMS (ESI) calcd for
DMSO-d6): 183.6, 146.1, 145.5, 137.5, 137.5, 134.6, 134.1,
129.2, 128.4, 126.6, 126.2, 124.6, 124.1, 122.2, 121.9, 120.1,
C20H17N2O+ [M + H]+ 301.1335, found 301.1337.
117.4, 115.4, 113.1, 109.8; HRMS (ESI) calcd for C22H16N3O+ [M
+ H]+ 338.1288, found 338.1290.
Conflicts of interest
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J. Name., 2013, 00, 1-3 | 7
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Journal Name
There are no conflicts to declare.
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Acknowledgements
Financial support to carry out this work from the Council of
Scientific and Industrial Research (CSIR) [02(351)/18/EMR-II],
India and for HRMS facility under DST-FIST from Department of
Science
&
Technology (DST) [SR/FST/CSI-270/2015] is
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20.
gratefully acknowledged.
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DOI: 10.1039/D0OB01842B
Table of Contents
X
R1
N
R1
X
N
O
K2S2O8 (3 equiv.)
N
+
N
Ar
COOH
DMSO/H2O, 60 oC, 3 h
O
Ar
X = CH, N
Metal free reaction conditions
Broad substrate scope
Scalable
25 examples
Yield: 50-85%