A Facile Synthesis of 3-(Arylthio)imidazo[1,2-a]pyridin-2(3H)-ones from 2-Aminopyridinium Bromides and Sodium Arenesulfinates

Article abstract of DOI:10.1002/ejoc.202000996

A simple and convenient method has been developed for the synthesis of 3-(arylthio)imidazo[1,2-a]pyridin-2(3H)-ones through a catalyst-free reaction of 2-aminopyridinium bromides with sodium arenesulfinates. A variety of 3-(arylthio)imidazo[1,2-a]pyridin-2(3H)-ones were obtained in moderate to excellent (33–85 %) yields. The developed protocol is operationally simple, exhibits a broad substrate scope with a wide range of functional groups, and is amenable for gram-scale synthesis.

Full text of DOI:10.1002/ejoc.202000996

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: A facile synthesis of 3-(arylthio)imidazo[1,2-a]pyridin-2(3H)-ones
from 2-aminopyridinium bromides and sodium arenesulfinates
Authors: Saroj Budania, Krishnan Rangan, and Anil Kumar
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000996
Link to VoR: https://doi.org/10.1002/ejoc.202000996
01/2020

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
A facile synthesis of 3-(arylthio)imidazo[1,2-a]pyridin-2(3H)-ones
from 2-aminopyridinium bromides and sodium arenesulfinates
Saroj,[a] Krishnan Rangan[b] and Anil Kumar*,[a]
[a]
Dr. Saroj, Prof. A. Kumar*
Department of Chemistry, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India
http://universe.bits-pilani.ac.in/pilani/anilkumar/Profile
E-mail: anilkumar@pilani.bits-pilani.ac.in
[b]
Prof. K. Rangan
Department of Chemistry, Birla Institute of Technology and Science Pilani, Hyderabad Campus, Telangana 500078, India
Supporting information (Copy of 1H & 13C NMR spectra of 3 and crystallographic data of 3aa) for this article is given via a link at the end of the document.
Abstract: A simple and convenient method has been developed for
the synthesis of 3-(arylthio)imidazo[1,2-a]pyridin-2(3H)-ones via a
catalyst-free reaction of 2-aminopyridinium bromides with sodium
arenesulfinates. A variety of 3-(arylthio)imidazo[1,2-a]pyridin-2(3H)-
ones were obtained in moderate to excellent (33-85%) yields. The
developed protocol is operationally simple, exhibits a broad substrate
scope with a wide range of functional groups, and is amenable for
gram‐scale synthesis.
Scheme 1. Synthesis of 3-(arylthio)imidazo[1,2-a]pyridin-2(3H)-ones.
Results and Discussion
Introduction
Our study begin by choosing 2-amino-1-(2-ethoxy-2-oxoethyl)-
pyridin-1-ium bromide (1a) and sodium p-toluenesulfinate (2a) as
the model substrates for optimizing the reaction conditions. Initial
reaction of 1a and 2a in CH3CN solvent at 110 °C for 15 h
produced 3-(p-tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3aa) in
40% yield (Table 1, entry 1). Structure of 3aa was elucidated with
the help of IR, NMR and mass data. A peak at 1643 cm-1 (C=Ostr)
in the IR spectrum and at 161.1 ppm in the 13C NMR spectrum of
3aa confirmed the presence of amidic C=O group.
Imidazo[1,2-a]pyridine is an important skeleton that has been
found to be present in many natural products, marketed drugs,
molecules with a diverse range of biological activities and
organometallics.[1] Due to their widespread applications in
materials and medicinal chemistry, considerable efforts have
been devoted toward the synthesis and functionalization of
imidazoheterocycles during the past decades.[2] Among them, the
development of efficient synthetic methods for sulfenylation has
attracted increasing attention of chemists due to considerable
therapeutic value of sulfenylated heteroarenes against a variety
of diseases.[3] Several reagents such as thiols,[4] disulfides,[5]
sulfonyl hydrazides,[6] thiosulfate salts,[7] sulfonyl halides,[8]
sulfinates,[9] sulfinic acid,[10] dithiocarbamates,[11] sulfenyl
chloride,[12] S‐phenyl benzenesulfonothioate,[13] sodium sulfide,[14]
thiocyanate,[15] DABSO [DABCO· (SO2)2][16] and elemental
sulfur[17] have been utilized for sulfenylation of Imidazo-
heterocycles under transition metal catalyzed and metal-free
conditions.[18] Among different sulfur sources, sodium
benzenesulfinate is a stable and odorless sulfur source.[19] Most
of these methods developed for the synthesis of 3-sulfenyl-
imidazo[1,2-a]pyridines utilize pre-synthesized imidazo[1,2-
a]pyridine moiety. There are only a few methods available in
which construction of imidazo[1,2-a]pyridine skeleton and
sulfenylation take place in one-pot.[20] Thus, the development of
new methods for the synthesis of 3-sulfenyl-imidazo[1,2-
a]pyridine derivatives under one-pot reaction conditions is highly
desirable. As part of our ongoing interest to explore the
applications of 2-aminopyridinium salt in organic synthesis,[21]
herein, we report a convenient method for the synthesis of 3-
(arylthio)imidazo[1,2-a]pyridin-2(3H)-ones (3) from 2-amino-
pyridinium bromides (1) and sodium arenesulfinates (2) under
catalyst- and base-free conditions (Scheme 1).
Table 1. Optimization of reaction conditions.[a]
S. No.
1.
Solvent
CH3CN
Temp. (°C)
110
Yield of 3aa (%)[b]
40
DCE
DCM
110
110
110
110
110
110
110
110
110
110
90
30
15
2.
3.
Acetone
DMF
38
4.
25
5.
H2O
20
6.
Dioxane
Toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
23
7.
15
8.
55[c]
82[d]
78[e]
70[d]
56[d]
75
9.
10.
11.
12.
60
13.
14.
130
[a]Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), solvent (3 mL), 15 h.
[b]Isolated yield. [c]1.5 mmol of 2a was used, [d]2.0 mmol of 2a was used, [e]2.5
mmol of 2a was used.
Encouraged with initial result, we examined the reaction
conditions by varying different solvents, amount of 2a, and
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
reaction temperature (Table 1, entries 2-14). Among all screened
solvents, acetonitrile was found to be the most suitable solvent for
this reaction. Pronounced effect on the reaction yield was
observed by increasing the amount of 2a. The yield of 3aa
increased from 40 to 82% on increasing the amount of 2a from
one equivalent to two equivalent (Table 1, entries 9-10). Further
increasing the amount of 2a did not increase the yield of desired
product, but led to slightly lower yields (Table 1, entry 11).
Performing the reaction at temperatures less than 110ꢀ°C resulted
in lower yields of 3aa (Table 1, entries 12-13). On the other hand,
increasing the temperature to 130ꢀ°C did not improve the yield of
3aa either (Table 1, entry 14).
Table 2. Substrate scope for sodium arenesulfinates and 2-aminopyridinium
bromides.[a,b]
To evaluate the general applicability of the developed protocol,
reaction of various 2-aminopyridinium bromides (1a-m) with
sodium arenesulfinates (2a-k) were performed under optimized
reaction conditions (Table 2). It was found that the arenesulfinates
possessing electron-donating groups on the aryl ring furnished
desired products in higher yields compared to those with electron-
withdrawing groups (3aa-3ae vs 3ag-3aj). Notably, halo groups
such as fluoro, chloro and bromo on the aryl ring of sulfinates
were well tolerated and provided corresponding products 3ah-3aj
in modest (44-50%) yields. Ortho-substituted arenesulfinates 1c
and 1k also reacted smoothly to afford 3ac and 3ak in 71% and
55% yields, respectively. Disappointingly, reaction of 1a with
sodium methanesulfinate did not produce corresponding 3-
(methylthio)imidazo[1,2-a]pyridin-2(3H)-one
under
these
conditions.
Next, substrate scope of 2-aminopyridinium bromides was
examined. 2-Aminopyridinium bromides substituted with groups
such as methyl, chloro, bromo, iodo, amino, aryl and heteroaryl
on the pyridine ring (1b-m) reacted with 2b to afford the
corresponding products 3bb-3mb in moderate to good (40-85%)
yields. Interestingly, substrate 1f with C5-bromo and C3-amino
groups on 2-aminopyridine ring furnished corresponding product
3fd in 85% yield. The reaction of 1d-m with other sodium
sulfinates (2a, 2f, 2i and 2k) also went smoothly to produce 3da-
3mk in moderate to good yields. Comparing the yield of 3ed and
3fd, we concluded that the presence of the electron-donating
group at C3 position of 2-aminopyridinium bromide increases the
rate of the reaction.
[a]Reaction conditions: 1 (1.0 mmol), 2 (2.0 mmol), CH3CN (3 mL), 110 ºC, 15 h.
[b]Isolated yield.
The practical applicability of the developed methodology was
demonstrated by performing the reaction of 1a with 2a on a 6
mmol scale. The desired product 3aa was obtained in 1.20 g
(78%) yield under the optimized reaction conditions (Scheme 2).
The IR, NMR and HRMS data of all the synthesized compounds
1
were in good agreement with the proposed structure. In the H
NMR spectra, C3-proton was not visible as it takes position on the
five member ring nitrogen to give zwitter ionic form and molecule
forms hydrogen bonded dimer. The structure of 3ab was
unambiguously confirmed by single-crystal X-ray analysis (Figure
1, CCDC No. 2012504). The compound crystallized in the
monoclinic P21/c space group and obtained in the zwitterion form.
Intermolecular hydrogen bonding dimeric structure is observed
with N2-H…O1 non-covalent bond length 1.838 Å (Supp. Info,
Figure S1).
Scheme 2. Gram scale synthesis of 3aa.
To understand the mechanism of the reaction, a series of control
experiments were executed (Scheme 3). Initially, when 2a was
heated at 110 ºC in acetonitrile for 5h, cyclized product,
imidazo[1,2-a]pyridin-2(3H)-one (4) was obtained in 59% yield
(Scheme 3a). The reaction of 4 with 2a afforded 3aa in 60% yield
(Scheme 3b). On the other hand, a reaction of 1a with S-aryl
arenethiosulfonate (6) and p-tolyl disulfide (7) produced 3aa in
38% and 7% yields, respectively under standard conditions
Figure 1. ORTEP diagram of the compound 3ab (CCDC No. 2012504). Thermal
ellipsoids were drawn at the 50% probability level.
2
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
(Scheme 3c & 3d). These results indicated that 6 could be the Conclusion
possible intermediates in this reaction. Further, the peaks at m/z
135.0603, 157.0358 and 279.0538 in the LC-HRMS (ESI)
analysis of the reaction mixture of 1a and 2a indicated the
formation of 4, p-toluenesulfinic acid (8) and 6 as intermediates.
The reaction of 1a and 2a was completely inhibited when
performed in the presence of TEMPO and BHT (Scheme 3e).
These results suggest the involvement of a free radical pathway
in this reaction. It is worth mentioning that on heating 2a under
standard conditions in the absence of 1a, the formation of 6 or 7
was not observed. Thus, HBr generated during the cyclization of
1a has an essential role for the reactivity of 2a.
In summary, a convenient catalyst-, metal-, and base-free method
has been developed for the preparation of 3-sulfenylimidazo[1,2-
a]pyridin-2-(3H)-ones from 2-aminopyridinium bromides and
sodium arenesulfinates under mild conditions. The method
allowed direct synthesis of 3-sulfenylimidazo[1,2-a]pyridin-2-
(3H)-ones in good to excellent yields with excellent functional
group tolerance. The reaction is supposed to proceed though
radical pathway. We believe that the developed method is
significant, owing to its potentially simple operational procedure
and amenability for gram‐scale synthesis.
Experimental Section
General information: The thin-layer chromatography (TLC) was
performed on 0.25 mm silica gel 60-F254, and visualized under a UV lamp.
Column chromatography was performed using silica gel (100−200 mesh)
using hexane/ethyl acetate as eluents. Melting points were measured
using an automatic capillary point apparatus and are uncorrected. The IR
spectra were recorded on an FT-IR instrument, and values are expressed
1
in cm−1. The H and 13C NMR spectra were obtained on a 400 MHz and
100 MHz spectrometer. Coupling constants and chemical shifts were
reported in hertz (Hz) and parts per million (ppm), respectively, relative to
the internal standard of tetramethylsilane (TMS). The HRMS were
analyzed by the electrospray ionization (ESI) method in positive mode on
a Q-TOF LC-MS spectrometer. Sodium sulfinates (2a, 2d, 2e, 2i and 2j)
were purchased from Alfa Aesar and used as received without further
purification. Other sodium sulfinates (2b, 2c, 2f-2h and 2k) were prepared
by heating appropriate sulfonyl chlorides with a mixture of sodium sulfite
and sodium bicarbonate in the water at 80 ºC.[24] All other chemicals and
solvents were purchased from commercial sources and used without
further purification.
Scheme 3. Control experiments.
Procedure for synthesis of 3-sulfenylimidazo[1,2-a]pyridin-2-(3H)-
ones (3).
Based on the control experiments and literature reports,[22]
a
An oven-dried round bottom flask (10 mL) was charged with 2-
aminopyridinium bromide (1, 1 mmol) and sodium sulfinate (2, 2 mmol) in
CH3CN (3 mL) solvent. The resulting reaction mixture was heated to 110
C with condenser for 15 h. Progress of the reaction was monitored by TLC
analysis. After completion, the reaction mixture was cooled down to room
temperature and the acetonitrile solvent was removed under vacuum. The
residue was diluted with water (10 mL) and the product extracted in ethyl
acetate (3 × 5 mL). The ethyl acetate layer was washed with the aqueous
layer (2 x 5 mL), dried over anhydrous sodium sulfate and evaporated
under reduced pressure. The crude product was purified by column
chromatography using ethyl acetate/hexane (9: 1, v/v) as an eluent.
plausible reaction mechanism for the formation of 3 is depicted in
scheme 4. Initially on heating 1a undergoes intramolecular
amidation to produce 4. The reaction of sodium sulfinate with in
situ generated Br2 or HBr/1a leads to the formation of
arenesulfenyl bromide (5). The reaction of 5 with 2 produces S-
aryl arenethiosulfonate (6), which was detected in LC-MS of the
reaction mixture. Homolytic cleavage of 5 or 6 under thermal
conditions yields sulfenyl radical A.[23] Finally, addition of sulfenyl
radical (A) to the enol form of 4 generates radical intermediate B,
which on proton abstraction leads to the formation of 3-
sulfenylimidazo[1,2-a]pyridin-2-(3H)-ones (3). Possibility of
electrophilic substitution of 4 by 5 or 6 cannot be ruled out,
although the radical-trapping experiments supports the radical
mechanism.
3-(p-Tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3aa): White solid; yield:
120 mg (82%); mp 205-209 ºC; FTIR v (max): 3741, 3008, 2920, 1612,
1512, 1327, 1265, 1072, 887, 748, 663, 516 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.17 (d, J = 6.6 Hz, 1H), 7.40-7.33 (m, 2H), 7.07-7.01 (m,
3H), 6.92 (d, J = 8.2 Hz, 2H), 2.21 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ = 165.8, 144.1, 140.4, 138.4, 135.1, 131.9, 130.8, 128.8, 119.2, 116.5,
91.8, 25.6; HRMS (ESI): m/z [M + H]+ calcd for C14H13N2OS: 257.0743;
found: 257.0752.
3-(Phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3ab): White solid; yield: 79
mg (57%); mp 187-190 °C; FTIR v (max): 3066, 2915, 1643, 1616, 1577,
1473, 1330, 1269, 1068, 887, 729, 659, 520 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.20 (d, J = 6.5 Hz, 1H), 7.42 – 7.34 (m, 2H), 7.26 (t, J =
7.5 Hz, 2H), 7.14 (t, J = 7.2 Hz, 1H), 7.04 (t, J = 6.0 Hz, 1H), 7.00 (d, J =
7.4 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ = 161.1, 139.3, 137.4, 129.8,
Scheme 4. Proposed mechanism for the formation of 3.
3
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
127.3, 126.2, 125.5, 124.1, 114.7, 111.6, 86.2; HRMS (ESI): m/z [M + H]+
3-((4-Bromophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3aj): Off white
solid; yield: 92 mg (50%); mp 235-238 ºC; FTIR v (max): 3062, 2925, 1643,
1620, 1512, 1465, 1072, 887, 756, 663, 524 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.19 (d, J = 6.4 Hz, 1H), 7.46-7.40 (m, 3H), 7.34 (d, J = 8.5
Hz, 1H), 7.06 (t, J = 6.6 Hz, 1H), 6.95 (d, J = 8.3 Hz, 2H); 13C NMR (100
MHz, DMSO-d6) δ = 161.0, 139.1, 137.2, 132.5, 127.7, 127.5, 124.2, 118.9,
114.9, 111.4, 85.3; HRMS (ESI): m/z [M + H]+ calcd for C13H10BrN2OS:
320.9692; found: 320.9666.
calcd for C13H11N2OS: 243.0587; found: 243.0581.
3-(o-Tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3ac): Off white solid; yield:
104 mg (71%); mp 250-253 ºC; FTIR v (max): 3741, 3026, 1616, 1525,
1336, 1273, 1070, 889, 749, 669, 516 cm-1; 1H NMR (400 MHz, DMSO-d6)
δ = 8.14 (d, J = 6.5 Hz, 1H), 7.42 – 7.35 (m, 2H), 7.21 (d, J = 7.1 Hz, 1H),
7.1 – 6.98 (m, 3H), 6.45 (d, J = 7.4 Hz, 1H), 2.43 (s, 3H); 13C NMR (100
MHz, DMSO-d6) δ = 166.0, 144.2, 140.6, 139.5, 135.8, 132.0, 131.9, 130.6,
129.0, 128.9, 119.4, 116.4, 89.8, 24.4; HRMS (ESI): m/z [M + H]+ calcd for
C14H13N2OS: 257.0743; found: 257.0709.
3-((2-Bromophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3ak): Off white
solid; yield: 101 mg (55% yield); mp 238-241 ºC; FTIR v (max): 3741, 3055,
2915, 1643, 1612, 1550, 1442, 1273, 894, 748, 655, 524 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ 8.14 (d, J = 6.3 Hz, 1H), 7.62 (d, J = 7.7 Hz, 1H),
7.45 (t, J = 7.8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.19 (t, J = 7.3 Hz, 1H),
7.10-7.05 (m, 2H), 6.44 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, DMSO-
d6) δ 161.1, 139.1, 137.9, 133.6, 128.8, 128.0, 127.6, 125.6, 124.2, 119.5,
115.1, 111.1, 84.3; HRMS (ESI): m/z [M + H]+ calcd for C13H10BrN2OS:
320.9692; found: 320.9695.
3-(m-Tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3ad): Off white solid;
yield: 94 mg (64%); mp 192-195 ºC; FTIR v (max): 3741, 3010, 1620, 1522,
1328, 1267, 1070, 886, 742, 662, 516 cm-1; 1H NMR (400 MHz, DMSO-
d6) δ = 8.18 (d, J = 6.3 Hz, 1H), 7.41 – 7.33 (m, 2H), 7.13 (t, J = 7.5 Hz,
1H), 7.04 (t, J = 6.3 Hz, 1H), 6.95 (d, J = 7.2 Hz, 1H), 6.88 (s, 1H), 6.76 (d,
J = 7.4 Hz, 1H), 2.20 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ = 161.2,
139.4, 139.1, 137.2, 129.6, 127.2, 127.0, 126.1, 124.1, 122.7, 114.5, 111.8,
86.5, 21.4; HRMS (ESI): m/z [M + H]+ calcd for C14H13N2OS: 257.0743;
found: 257.0711.
8-Methyl-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3bb): Off white
solid; yield: 77 mg (55%); mp 230-233 ºC; FTIR v (max): 3741, 3062, 2920,
1616, 1597, 1573, 1473, 1234, 1080, 879, 840, 748, 686, 586 cm-1; 1H
NMR (400 MHz, DMSO-d6) δ = 8.03 (d, J = 6.4 Hz, 1H), 7.26-7.20 (m, 3H),
7.12 (t, J = 7.2 Hz, 1H), 6.99 – 6.92 (m, 3H), 2.42 (s, 3H); 13C NMR (100
MHz, DMSO-d6) δ = 161.2, 139.9, 137.4, 129.7, 127.6, 126.9, 126.1, 125.5,
121.9, 114.3, 86.6, 16.3; HRMS (ESI): m/z [M + H]+ calcd for C14H13N2OS:
257.0743; found: 257.0740.
3-((4-Methoxyphenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3ae): White
solid; yield: 131mg (84%); mp 203-205 ºC; FTIR v (max): 3741, 3008, 2954,
1643, 1620, 1512, 1489, 1242, 1033, 887, 748, 663, 524 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.24 (d, J = 6.6 Hz, 1H), 7.39-7.31 (m, 2H), 7.07-
7.02 (m, 3H), 6.85 (d, J = 8.7 Hz, 2H), 3.68 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ = 160.9, 158.5, 139.1, 128.4, 127.5, 127.0, 124.0, 115.5,
114.4, 111.8, 88.2, 55.6; HRMS (ESI): m/z [M + H]+ calcd for C14H13N2O2S:
273.0692; found: 273.0680.
7-Methyl-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3cb): Off white
solid; yield: 78 mg (56%); mp 188-191 ºC; FTIR v (max): 3062, 2962, 1654,
1593, 1543, 1473, 1265, 1080, 887, 736, 690, 586 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.06 (d, J = 6.6 Hz, 1H), 7.25 (t, J = 7.4 Hz, 2H), 7.15-7.11
3-((4-(tert-Butyl)phenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3af): Off
white solid; yield: 92 mg (54%); mp 180-184 ºC; FTIR v (max): 3010, 2960,
1616, 1473, 1458, 1328, 1072, 883, 748, 663, 501 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.22 (d, J = 6.2 Hz, 1H), 7.40 – 7.33 (m, 2H), 7.27 (d, J =
8.0 Hz, 2H), 7.03 (t, J = 6.0 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 1.20 (s, 9H);
13C NMR (100 MHz, DMSO-d6) δ = 161.1, 148.9, 139.5, 134.0, 127.1,
126.7, 125.7, 124.1, 114.5, 111.9, 87.0, 34.6, 31.5; HRMS (ESI): m/z [M +
H]+ calcd for C17H19N2OS: 299.1213; found: 299.1194.
(m, 2H), 6.98 (d, J = 7.6 Hz, 2H), 6.93 (d, J = 6.8 Hz, 1H), 2.36 (s, 3H); 13
C
NMR (100 MHz, DMSO-d6) δ = 160.9, 138.8, 137.9, 129.7, 126.0, 125.3,
123.6, 116.7, 110.3, 84.4, 21.1; HRMS (ESI): m/z [M + H]+ calcd for
C14H13N2OS: 257.0743; found: 257.0738.
6-Methyl-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3db): Off white
solid; yield: 70 mg, (50%); mp 237-241 ºC; FTIR v (max): 3741, 3039, 2915,
1647, 1597, 1512, 1465, 1311, 1072, 887, 756, 655, 578 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.05 (s, 1H), 7.26 (t, J = 6.7 Hz, 4H), 7.14 (t, J =
7.4 Hz, 1H), 6.99 (d, J = 7.1 Hz, 2H), 2.26 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ = 160.9, 137.8, 137.4, 129.7, 129.6, 126.1, 125.4, 124.3,
122.2, 110.8, 85.8, 18.0; HRMS (ESI): m/z [M + H]+ calcd for C14H13N2OS:
257.0743, found: 257.0746.
3-((4-Nitrophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3ag): Yellow solid;
yield: 57 mg (35%); mp 210-213 ºC; 1H NMR (400 MHz, DMSO-d6) δ =
8.19 (d, J = 6.5 Hz, 1H), 8.12 (d, J = 8.8 Hz, 2H), 7.47 (t, J = 7.7 Hz, 1H),
7.37 (d, J = 8.6 Hz, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.08 (t, J = 6.6 Hz, 1H);
13C NMR (100 MHz, DMSO-d6) δ = 160.93, 147.8, 145.7, 139.7, 128.3,
125.5, 124.9, 124.3, 115.2, 111.1, 83.3; FTIR v (max): 3741, 3060, 2978,
1620, 1573, 1496, 1334, 1080, 840, 740, 671, 524 cm-1; HRMS (ESI): m/z
[M + H]+ calcd for C13H10N3O3S: 288.0437; found: 288.0432.
6-Chloro-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3eb): Off white
solid; yield: 94 mg (67%); mp 239-242 ºC; FTIR v (max): 3741, 3008, 2924,
1604, 1558, 1512, 1465, 1296, 1064, 879, 748, 655, 563 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.29 (s, 1H), 7.43 (d, J = 1.4 Hz, 2H), 7.28 (t, J
= 7.7 Hz, 2H), 7.17 (t, J = 7.4 Hz, 1H), 7.02 (d, J = 7.4 Hz, 2H); 13C NMR
(100 MHz, DMSO-d6) δ = 162.0, 139.4, 136.6, 129.9, 127.2, 126.4, 125.8,
3-((4-Fluorophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3ah): Off white
solid; yield: 66 mg (44%); mp 215-218 ºC; FTIR v (max): 3047, 1643, 1614,
1485, 1267, 1209, 1076, 873, 750, 661, 524, 426 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.23 (d, J = 6.4 Hz, 1H), 7.40 (t, J = 8 Hz, 1H), 7.33 (d, J =
8.4 Hz, 1H), 7.15 – 7.03 (m, 5H); 13C NMR (100 MHz, DMSO-d6) δ = 165.9
(d, JC-F = 248 Hz), 165.8, 143.9, 137.7, 132.7 (d, JC-F = 1.2 Hz), 132.2,
128.8 (d, JC-F = 4.6 Hz), 128.8, 121.6, 120.4, (d, JC-F = 21.2 Hz), 116.3,
91.4; 19F NMR (376 MHz, DMSO-d6) δ = -108.89, -112.35; HRMS (ESI):
m/z [M + H]+ calcd for C13H10FN2OS: 261.0492; found: 261.0453.
121.8, 120.8, 114.0, 89.0; HRMS (ESI): m/z [M
+
H]+ calcd for
C13H10ClN2OS: 277.0197; found: 277.0204.
6-Bromo-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3fb): Off white
solid; yield: 99 mg (70%); mp 237-240 ºC; FTIR v (max): 3741, 3062, 2933,
1612, 1558, 1512, 1465, 1303, 1056, 794, 740, 648, 570 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.32 (d, J = 1.3 Hz, 1H), 7.51 (dd, J = 9.2, 1.8
Hz, 1H), 7.37 (d, J = 9.2 Hz, 1H), 7.28 (t, J = 7.5 Hz, 2H), 7.17 (t, J = 7.3
Hz, 1H), 7.02 (d, J = 7.4 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ = 161.9,
139.5, 136.6, 129.9, 129.5, 126.4, 125.8, 123.7, 114.3, 107.5, 88.8; HRMS
(ESI): m/z [M + H]+ calcd for C13H10BrN2OS: 320.9692; found: 320.9689.
3-((4-Chlorophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3ai): Off white
solid; yield: 75 mg (47%); mp 232-235 ºC; FTIR v (max): 3741, 3024, 2978,
1643, 1620, 1512, 1419, 1265, 1080, 887, 756, 663, 524 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.19 (d, J = 6.2 Hz, 1H), 7.42 (t, J = 7.6, 1H),
7.35-7.31 (m, 3H), 7.07-7.01 (m, 3H); 13C NMR (100 MHz, DMSO-d6) δ =
161.0, 139.1, 136.6, 130.7, 129.7, 127.7, 127.2, 124.2, 114.9, 111.4, 85.5;
HRMS (ESI): m/z [M + H]+ calcd for C13H10ClN2OS: 277.0197; found:
277.0168.
6-Iodo-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3gb): Off white
solid; yield: 99 mg (69%); mp 235-238 ºC; FTIR v (max): 3741, 3062, 2962,
1681, 1612, 1558, 1465, 1296, 1018, 794, 740, 648 cm-1; 1H NMR (400
MHz, DMSO-d6) δ = 8.32 (s, 1H), 7.59 (d, J = 8.6 Hz, 1H), 7.30-7.22 (m,
4
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
3H), 7.17 (t, J = 7.0 Hz, 1H), 7.02 (d, J = 7.4 Hz, 2H); 13C NMR (100 MHz,
DMSO) δ = 161.4, 139.4, 136.8, 134.4, 129.9, 128.1, 126.4, 125.7, 114.3,
87.8, 77.6; HRMS (ESI): m/z [M + H]+ calcd for C13H10IN2OS: 368.9553;
found: 368.9524.
1558, 1465, 1319, 1242, 1112, 884, 756, 655, 524 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.03 (s, 1H), 7.24 (s, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.91 (d,
J = 8.0 Hz, 2H), 2.26 (s, 3H), 2.22 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ = 161.0, 137.5, 135.5, 134.1, 130.3, 129.4, 125.8, 124.1, 122.1, 111.0,
86.5, 20.9, 18.0; HRMS (ESI): m/z [M + H]+ calcd for C15H15N2OS:
271.0900; found: 271.0891.
8-Amino-6-bromo-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3hb):
Off white solid, yield: 114 mg (80%); mp 241-244 ºC; FTIR v (max): 3741,
3448, 3140, 2970, 1705, 1658, 1597, 1566, 1419, 1257, 1018, 995, 879,
756, 686, 601 cm-1; 1H NMR (400 MHz, DMSO-d6) δ = 7.56 (d, J = 1.7 Hz,
1H), 7.28 (t, J = 7.5 Hz, 2H), 7.17 (t, J = 7.3 Hz, 1H), 7.00 (d, J = 7.3 Hz,
2H), 6.58 (d, J = 1.7 Hz, 1H), 5.85 (s, 2H); 13C NMR (100 MHz, DMSO-d6)
δ = 160.8, 137.0, 136.4, 133.1, 129.9, 126.3, 125.7, 111.7, 108.5, 107.2,
89.6; HRMS (ESI): m/z [M + H]+ calcd for C13H11BrN3OS: 335.9801; found:
335.9768.
6-Bromo-3-(p-tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3fa): Off white
solid; yield: 65 mg (44%); mp 232-235 ºC; FTIR v (max): 3741, 3039, 2950,
1643, 1581, 1496, 1311, 1056, 802, 648, 565 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.28 (d, J = 1.3 Hz, 1H), 7.49 (dd, J = 9.2, 1.9 Hz, 1H), 7.36
(d, J = 9.2 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.2 Hz, 2H), 2.22
(s, 3H); 13C NMR (100 MHz, DMSO-d6) δ = 161.8, 139.4, 136.0, 132.9,
130.5, 129.3, 126.3, 123.6, 114.3, 107.4, 89.5, 20.9; HRMS (ESI): m/z [M
+ H]+ calcd for C14H12BrN2OS: 334.9848; found: 334.9840.
6-Phenyl-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3ib): White solid;
yield: 103 mg (73%); mp 212-215 ºC; FTIR v (max): 3062, 2985, 1643,
1620, 1512, 1473, 1265, 1072, 887, 756, 663, 524 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 8.30 (s, 1H), 7.71 (dd, J = 8.9, 1.1 Hz, 1H), 7.59 (d, J = 7.4
Hz, 2H), 7.46 (t, J = 8.1 Hz, 3H), 7.38 (t, J = 7.2 Hz, 1H), 7.26 (t, J = 7.5
Hz, 2H), 7.13 (t, J = 7.3 Hz, 1H), 7.05 (d, J = 7.5 Hz, 2H); 13C NMR (100
MHz, DMSO-d6) δ = 161.7, 139.2, 137.2, 136.7, 129.8, 129.7, 128.4, 127.5,
127.0, 126.6, 126.3, 125.7, 120.7, 112.4, 87.5; HRMS (ESI): m/z [M + H]+
calcd for C19H15N2OS: 319.0900; found: 319.0907.
8-Amino-6-bromo-3-(p-tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3ha): Off
white solid; yield: 126 mg (85%); mp 272-235 ºC; FTIR v (max): 3414, 3199,
1
2924, 1654, 1587, 1570, 1489, 1274, 1068, 877, 750, 675, 551 cm-1; H
NMR (400 MHz, DMSO-d6) δ = 7.53 (s, 1H), 7.09 (d, J = 7.4 Hz, 2H), 6.91
(d, J = 7.4 Hz, 2H), 6.55 (s, 1H), 5.86 (s, 2H), 2.22 (s, 3H); 13C NMR (100
MHz, DMSO-d6) δ = 160.8, 136.3, 135.8, 133.3, 133.0, 130.5, 126.1, 111.7,
108.4, 107.0, 90.1, 20.9; HRMS (ESI): m/z [M
+
H]+ calcd for
C14H13BrN3OS: 349.9957; found: 349.9918.
6-(4-Methoxyphenyl)-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one
(3jb): White solid; yield: 90 mg (63%); mp 227-230 ºC; FTIR v (max): 3741,
3047, 2955, 1604, 1566, 1473, 1249, 1172, 1026, 825, 794, 663, 532 cm-
1; 1H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.69 (d, J = 9.1 Hz, 1H),
7.50 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 9.0 Hz, 1H), 7.24 (t, J = 7.7 Hz, 2H),
7.12 (t, J = 7.3 Hz, 1H), 7.02 (t, J = 8.9 Hz, 4H), 3.75 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 161.4, 159.7, 138.6, 137.2, 129.8, 128.9, 128.2,
127.4, 126.5, 126.2, 125.6, 120.0, 115.1, 112.0, 87.1, 55.7 cm-1; HRMS
(ESI): m/z [M + H]+ calcd for C20H17N2O2S: 349.1005; found: 349.1004.
6-Phenyl-3-(p-tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3ia): Off white
solid; yield: 89 mg (61%); mp 230-233 ºC; FTIR v (max): 3741, 3070, 2985,
1643, 1604, 1519, 1319, 1227, 1080, 810, 756, 663, 516 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.72 (d, J = 9.1 Hz, 1H), 7.62 (d, J =
7.6 Hz, 2H), 7.47 (t, J = 8.3 Hz, 3H), 7.40 (t, J = 7.3 Hz, 1H), 7.09 (d, J =
7.9 Hz, 2H), 6.98 (d, J = 7.8 Hz, 2H), 2.21 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 161.5, 146.2, 136.7, 135.8, 133.4, 130.5, 129.7, 128.5, 127.5,
127.0, 126.5, 126.1, 122.5, 120.6, 112.3, 86.3, 21.1; HRMS (ESI): m/z [M
+ H]+ calcd for C20H17N2OS: 333.1056; found: 333.1043.
6-(4-Chlorophenyl)-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3kb):
Off white solid; yield: 107 mg (75%); mp 245-248 ºC; FTIR v (max): 3741,
6-(1H-Indol-1-yl)-3-(p-tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3la): Off
white solid; yield: 98 mg (66%); mp 224-227 ºC; FTIR v (max): 3741, 3047,
1604, 1566, 1473, 1249, 1172, 1026, 889, 748, 655, 524 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.25 (s, 1H), 7.65 - 7.55 (m, 4H), 7.13 – 7.05 (m,
5H), 6.98 (d, J = 7.9 Hz, 2H), 6.70 (d, J = 2.7 Hz, 1H), 2.23 (s, 3H); 13C
NMR (100 MHz, DMSO-d6) δ 162.0, 136.1, 136.0, 132.5, 130.5, 129.3,
129.2, 127.9, 126.5, 124.5, 122.9, 121.5, 121.0, 119.2, 113.4, 110.2, 104.3,
89.4, 20.9; HRMS (ESI): m/z [M + H]+ calcd for C22H18N3OS: 372.1165;
found: 372.1152.
1
3023, 2978, 1612, 1558, 1473, 1319, 1010, 802, 748, 694, 532 cm-1; H
NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.73 (d, J = 9.0, Hz, 1H), 7.62
(d, J = 8.2 Hz, 2H), 7.51-7.44 (m, 3H), 7.24 (t, J = 7.6 Hz, 2H), 7.13 (t, J =
7.3 Hz, 1H), 7.03 (d, J = 7.7 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ
161.7, 137.2, 135.6, 133.3, 130.0, 129.8, 129.6, 128.9, 127.7, 126.4, 126.3,
125.7, 120.9, 112.6, 87.7; HRMS (ESI): m/z [M
+
H]+ calcd for
C19H14ClN2OS: 353.0510; found: 353.0513.
6-(1H-Indol-1-yl)-3-(phenylthio)imidazo[1,2-a]pyridin-2(3H)-one (3lb): Off
white solid; yield: 78 mg (55%); mp 238-241 ºC; FTIR v (max): 3741, 3047,
1604, 1566, 1473, 1249, 1172, 1026, 894, 748, 655, 524 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.28 (s, 1H), 7.64 – 7.56 (m, 4H), 7.29 (t, J = 6
Hz, 2H), 7.19 (t, J = 7.3 Hz, 2H), 7.13-7.07 (m, 4H), 6.69 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ = 162.1, 139.0, 136.3, 136.1, 129.9, 129.3, 128.0,
126.5, 126.1, 124.6, 122.9, 121.5, 120.9, 119.4, 113.4, 110.2, 104.3, 88.9;
HRMS (ESI): m/z [M + H]+ calcd for C21H16N3OS: 358.1009; found:
358.0988.
6-(1H-Pyrazol-1-yl)-3-(p-tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3ma):
Off white solid; yield: 62 mg (42%); mp 260-263 ºC; FTIR v (max): 3116,
3010, 1616, 1558, 1489, 1398, 1249, 1192, 1080, 883, 742, 657, 518 cm-
1
1; H NMR (400 MHz, DMSO) δ = 8.61 (s, 1H), 8.53 (s, 1H), 7.91 (d, J =
9.1 Hz, 1H), 7.74 (s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.08 (d, J = 7.6 Hz, 2H),
6.96 (d, J = 7.7 Hz, 2H), 6.55 (s, 1H), 2.21 (s, 3H); 13C NMR (100 MHz,
DMSO) δ = 162.0, 141.8, 138.7, 135.9, 133.1, 130.5, 129.8, 129.0, 126.0,
119.0, 114.1, 113.2, 108.6, 89.4, 20.9; HRMS (ESI): m/z [M + H]+ calcd for
C17H15N4OS: 323.0961; found: 323.0953.
3-(Phenylthio)-6-(1H-pyrazol-1-yl)imidazo[1,2-a]pyridin-2(3H)-one (3mb):
Off white solid; yield: 56 mg (40%); mp 245-248 ºC; FTIR v (max): 3741,
3-((4-(tert-Butyl)phenyl)thio)-6-methylimidazo[1,2-a]pyridin-2(3H)-one
(3df): Off white solid; yield: 68 mg (40%); mp 225-228 ºC; FTIR v (max):
3010, 2953, 1608, 1558, 1473, 1276, 1014, 817, 750, 659, 538 cm-1; H
1
1
3124, 2978, 1604, 1527, 1396, 1188, 1049, 887, 740, 665, 563 cm-1; H
NMR (400 MHz, DMSO-d6) δ = 8.62 (d, J = 1.2 Hz, 1H), 8.54 (d, J = 2.2
Hz, 1H), 7.93 (dd, J = 9.3, 1.8 Hz, 1H), 7.73 (s, 1H), 7.53 (d, J = 9.3 Hz,
1H), 7.27 (t, J = 7.6 Hz, 2H), 7.15 (t, J = 7.2 Hz, 1H), 7.04 (d, J = 7.5 Hz,
2H), 6.55 (t, J = 2.1 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ = 162.1,
141.9, 138.8, 136.9, 129.9, 129.0, 126.3, 125.6, 119.1, 114.1, 113.1, 108.6,
88.8; HRMS (ESI): m/z [M + H]+ calcd for C16H13N4OS: 309.0805; found:
309.0785.
NMR (400 MHz, DMSO-d6) δ = 8.08 (s, 1H), 7.28 – 7.24 (m, 4H), 6.93 (d,
J = 8.2 Hz, 2H), 2.26 (s, 3H), 1.20 (s, 9H); 13C NMR (100 MHz, DMSO-d6)
δ = 160.5, 148.9, 136.5, 134.3, 129.8, 126.6, 125.6, 124.6, 122.2, 110.3,
86.4, 34.5, 31.5, 18.0; HRMS (ESI): m/z [M + H]+ calcd for C18H21N2OS:
313.1369; found: 313.1361.
6-Bromo-3-((4-(tert-butyl)phenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one
(3ff): Off white solid; yield: 97 mg (58%); mp 258-261 ºC; FTIR v (max):
3062, 2949, 1616, 1560, 1463, 1301, 1213, 1012, 804, 731, 540 cm-1; 1H
NMR (400 MHz, DMSO-d6) δ = 8.35 (s, 1H), 7.49 (dd, J = 9.2, 1.5 Hz, 1H),
6-Methyl-3-(p-tolylthio)imidazo[1,2-a]pyridin-2(3H)-one (3da): Off white
solid; yield: 93 mg (63%); mp 235-238 ºC; FTIR v (max): 3341, 3047, 1604,
5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
7.37 (d, J = 9.2 Hz, 1H), 7.29 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 8.3 Hz, 2H),
1.20 (s, 9H); 13C NMR (100 MHz, DMSO-d6) δ = 161.8, 149.2, 139.5, 133.2,
129.3, 126.8, 125.9, 123.7, 114.4, 107.4, 89.5, 34.6, 31.5; HRMS (ESI):
m/z [M + H]+ calcd for C17H18BrN2OS: 377.0318; found 377.0285.
119.4, 110.5, 83.9, 17.9; HRMS (ESI): m/z [M +
H]+ calcd for
C14H12BrN2OS: 334.9848; found: 334.9841
6-Bromo-3-((2-bromophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one (3fk):
Off white solid; yield 109 mg (62%); mp 242-245 ºC; FTIR v (max): 3741,
3070, 1643, 1597, 1419, 1296, 1018, 810, 748, 624 cm-1; 1H NMR (400
MHz, DMSO-d6) δ = 8.27 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.56 (d, J = 8.9
Hz, 1H), 7.38 (d, J = 9.0 Hz, 1H), 7.20 (t, J = 7.2 Hz, 1H), 7.10 (t, J = 7.2
Hz, 1H), 6.45 (d, J = 7.5 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ = 161.8,
139.5, 137.4, 133.6, 130.0, 129.0, 127.8, 125.8, 123.9, 119.6, 113.8, 107.9,
86.9; HRMS (ESI): m/z [M + H]+ calcd for C13H9Br2N2OS: 398.8797; found
398.8767.
3-((4-(tert-Butyl)phenyl)thio)-6-phenylimidazo[1,2-a]pyridin-2(3H)-one
(3if): Off white solid; yield: 70 mg (42%); mp 228-231 ºC; FTIR v (max):
3010, 2975, 1643, 1608, 1473, 1276, 1014, 887, 810, 659, 538 cm-1; H
NMR (400 MHz, DMSO-d6) δ = 8.34 (s, 1H), 7.71 (d, J = 8.7 Hz, 1H), 7.61
(d, J = 7.2 Hz, 2H), 7.47 (t, J = 4.8 Hz, 3H), 7.39 (t, J = 7 Hz, 1H), 7.27 (d,
J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 1.18 (s, 9H); 13C NMR (100 MHz,
DMSO-d6) δ = 166.2, 153.8, 143.8, 141.4, 138.5, 134.4, 133.2, 132.2,
131.8, 131.5, 131.3, 130.6, 125.4, 117.2, 92.8, 39.3, 36.2; HRMS (ESI):
m/z [M + H]+ calcd for C23H23BN2OS: 375.1526; found: 375.1513.
1
3-((2-Bromophenyl)thio)-6-phenylimidazo[1,2-a]pyridin-2(3H)-one (3ik):
Off white solid; yield: 100 mg (57%); mp 242-245 ºC; FTIR v (max): 3080,
2916, 1643, 1565, 1435, 1265, 1157, 1018, 810, 740, 624 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 8.29 (s, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.67-7.60
(m, 3H), 7.51 (t, J = 6.8 Hz, 4H), 7.18 (t, J = 6.9 Hz, 1H), 7.07 (t, J = 6.9
Hz, 1H), 6.50 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ = 161.6,
139.4, 137.9, 135.4, 133.6, 133.4, 129.6, 129.0, 128.9, 127.7, 127.0, 127.0,
125.8, 121.0, 119.6, 112.2, 85.9; HRMS (ESI): m/z [M + H]+ calcd for
C19H14BrN2OS: 397.0005; found: 397.9956.
3-((4-Chlorophenyl)thio)-6-methylimidazo[1,2-a]pyridin-2(3H)-one (3di):
White solid; yield: 65 mg (41%); mp 245-248 ºC; FTIR v (max): 3741, 2985,
1643, 1604, 1473, 1087, 956, 802, 572 cm-1; 1H NMR (400 MHz, DMSO-
d6) δ = 8.04 (s, 1H), 7.33-7.23 (m, 4H), 7.01 (d, J = 8.5 Hz, 2H), 2.26 (s,
3H); 13C NMR (100 MHz, DMSO-d6) δ = 160.9, 137.1, 137.0, 130.6, 129.9,
129.6, 127.1, 124.6, 122.2, 110.5, 85.1, 18.0; HRMS (ESI): m/z [M + H]+
calcd for C14H12ClN2OS: 291.0353; found: 291.0315.
6-Bromo-3-((4-chlorophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-one
(3fi):
3-((2-Bromophenyl)thio)-6-(4-methoxyphenyl)imidazo[1,2-a]pyridin-
2(3H)-one (3jk): Off white solid; yield: 88 mg (51%); mp 227-230 ºC; FTIR
v (max): 3085, 2989, 1653, 1610, 1558, 1489, 1317, 1261, 1093, 806, 748,
642, 418 cm-1; 1H NMR (400 MHz, DMSO-d6) δ = 8.11 (s, 1H), 7.73 (d, J
= 9.0 Hz, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 8.3 Hz, 2H), 7.42 (d, J
= 9.0 Hz, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.06 (t, J = 7.6 Hz, 1H), 6.99 (d, J =
8.4 Hz, 2H), 6.53 (d, J = 8.0 Hz, 1H), 3.74 (s, 3H); 13C NMR (100 MHz,
DMSO) δ = 160.7, 159.8, 158.7, 139.5, 137.6, 133.6, 128.9, 128.5, 128.3,
128.1, 127.9, 127.6, 125.9, 120.0, 119.7, 115.2, 85.2, 55.7; HRMS (ESI):
m/z [M + H]+ calcd for C20H16BrN2O2S: 427.0110; found: 427.0096.
White solid; yield: 77 mg (60%); mp 234-237 ºC; FTIR v (max): 3741, 2987,
1642, 1608, 1473, 1086, 956, 799, 571 cm-1; 1H NMR (400 MHz, DMSO-
d6) δ = 8.34 (s, 1H), 7.52 (d, J = 9.0 Hz, 1H), 7.37 – 7.32 (m, 3H), 7.04 (d,
J = 8.2 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ = 161.8, 139.3, 135.9,
131.0, 129.8, 127.6, 123.8, 114.0, 107.7, 88.2; HRMS (ESI): m/z [M + H]+
calcd for C13H9ClBrN2OS: 354.9302; found: 354.9269.
8-Amino-6-bromo-3-((4-chlorophenyl)thio)imidazo[1,2-a]pyridin-2(3H)-
one (3hi): Off white solid; yield: 109 mg (70%); mp 245-247 ºC; FTIR v
(max): 3414, 3033, 2967, 1623, 1567, 1473, 1069, 887, 551 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ = 7.56 (d, J = 1.8 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H),
6.99 (d, J = 8.4 Hz, 2H), 6.58 (d, J = 1.7 Hz, 1H), 5.89 (s, 2H); 13C NMR
(100 MHz, DMSO) δ = 160.9, 136.3, 136.2, 133.0, 130.9, 129.8, 127.4,
Procedure for synthesis of imidazo[1,2-a]pyridin-2(3H)-one (4).
An oven-dried round bottom flask (10 mL) was charged with 2-
aminopyridinium bromide (1a, 1.0 mmol) in CH3CN (3 mL) solvent. The
resulting reaction mixture was heated to 110 C with condenser for 5 h.
After completion, the reaction mixture was cooled down to room
temperature and the acetonitrile solvent was removed under vacuum. The
residue was washed with diethyl ether (2 × 5 mL) and the solid was dried
under reduced pressure to give 4.
111.7, 108.7, 107.5, 88.9; HRMS (ESI): m/z [M
+
H]+ calcd for
C13H10BrClN3OS: 369.9411; found: 369.9395.
3-((4-Chlorophenyl)thio)-6-phenylimidazo[1,2-a]pyridin-2(3H)-one
Off white solid; yield: 85 mg (54%); mp 248-251 ºC; FTIR v (max): 3018,
2954, 1637, 1606, 1558, 1473, 1274, 1087, 815, 756, 661, 518 cm-1; H
(3ii):
1
NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.62
(d, J = 7.5 Hz, 2H), 7.47 (t, J = 6.9 Hz, 3H), 7.40 (t, J = 7.1 Hz, 1H), 7.32
(d, J = 8.4 Hz, 2H), 7.06 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, DMSO-
d6) δ 161.6, 136.6, 136.5, 130.8, 129.7, 129.6, 128.5, 127.7, 127.4, 127.1,
Imidazo[1,2-a]pyridin-2(3H)-one (4):[25] Off white solid; yield: 79 mg (59%);
FTIR v (max): 3121, 2967, 1626, 914, 885, cm-1; 1H NMR (400 MHz,
DMSO-d6) δ 1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 6.4 Hz, 1H), 8.41
(t, J = 8.2 Hz, 1H), 7.60 – 7.55 (m, 2H), 5.30 (s, 2H).
126.9, 120.7, 112.2, 86.7; HRMS (ESI): m/z [M
+
H]+ calcd for
C19H14ClN2OS: 353.0510; found: 353.0500.
3-((4-Chlorophenyl)thio)-6-(1H-pyrazol-1-yl)imidazo[1,2-a]pyridin-2(3H)-
one (3mi): White solid; yield: 55 mg (35%); mp 255-259 ºC; FTIR v (max):
3741, 3008, 2927, 1620, 1606, 1558, 1469, 1274, 1010, 835, 756, 661,
518 cm-1; 1H NMR (400 MHz, DMSO-d6) δ = 8.57 (s, 1H), 8.45 (s, 1H),
7.92 (d, J = 9.3 Hz, 1H), 7.73 (s, 1H), 7.48 (d, J = 9.4 Hz, 1H), 7.30 (d, J =
8.2 Hz, 2H), 7.06 (d, J = 8.2 Hz, 2H), 6.55 (s, 1H); 13C NMR (100 MHz,
DMSO) δ = 161.5, 142.0, 137.7, 136.1, 131.0, 130.3, 129.8, 129.0, 127.3,
119.5, 114.1, 112.3, 108.7, 87.8; HRMS (ESI): m/z [M + H]+ calcd for
C16H12ClN4OS: 343.0415; found 343.0399.
Acknowledgments
Financial support from Department of Science and Technology,
New Delhi under DST-FIST [SR/FST/CSI-270/2015] for HRMS
facility to Department of Chemistry, BITS Pilani is acknowledged.
Keywords: 2-aminopyridinium salt • amidation • cyclization •
imidazo[1,2-a]pyridine-2(3H)one • sulfenylation.
3-((2-Bromophenyl)thio)-6-methylimidazo[1,2-a]pyridin-2(3H)-one (3dk):
Off white solid; yield: 60 mg (33%); mp 252-255 ºC; FTIR v (max): 3741,
2972, 1643, 1604, 1512, 1303, 1087, 810, 740, 640, 578 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ 7.98 (s, 1H), 7.61 (dd, J = 7.8, 1.2 Hz, 1H), 7.33 –
7.25 (m, 2H), 7.18 (dt, J = 7.5, 1.3 Hz, 1H), 7.08 (dt, J = 7.7, 1.6 Hz, 1H),
6.44 (dd, J = 7.9, 1.4 Hz, 1H), 2.26 (s, 3H); 13C NMR (100 MHz, DMSO-
d6) δ 161.0, 138.3, 137.5, 133.5, 130.2, 128.8, 127.5, 125.5, 124.7, 122.3,
[1] (a) N. Devi, D. Singh, R. K Rawal, J. Bariwal, V. Singh, Curr.
Top. Med. Chem. 2016, 16, 2963-2994; (b) D. Aakash, B.
Richa Kaur, K. Ramanjot, K. Sanjiv, J. Upendra Kumar, S.
Harinder, B. Sandeep, K. Dinesh, D. Pran Kishore, Curr. Top.
Med. Chem. 2017, 17, 238-250; (c) C. Enguehard-Gueiffier,
A. Gueiffier, Mini Rev. Med. Chem. 2007, 7, 888-899; (d) S.
Feng, D. Hong, B. Wang, X. Zheng, K. Miao, L. Wang, H. Yun,
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
L. Gao, S. Zhao, H. C. Shen, ACS Med. Chem. Lett. 2015, 6,
[13] C. Ravi, A. Joshi, S. Adimurthy, Eur. J. Org. Chem. 2017
,
359-362; (e) G. Song, Y. Zhang, X. Li, Organometallics 2008
,
2017, 3646-3651.
27, 1936-1943.
[14] S. M. A. Shakoor, D. S. Agarwal, S. Khullar, S. K. Mandal, R.
Sakhuja, Chem. Asian J. 2017, 12, 3061-3068.
[15] J. Wen, C. Niu, K. Yan, X. Cheng, R. Gong, M. Li, Y. Guo, J.
Yang, H. Wang, Green Chem. 2020, 22, 1129-1133.
[16] J. Le Bescont, C. Breton-Patient, S. Piguel, Eur. J. Org.
Chem. 2020, 2020, 2101-2109.
[2] (a) K. Pericherla, P. Kaswan, K. Pandey, A. Kumar, Synthesis
2015, 47, 887-912; (b) A. K. Bagdi, S. Santra, K. Monir, A.
Hajra, Chem. Commun. 2015, 51, 1555-1575; (c) G. K. Reen,
A. Kumar, P. Sharma, Beilstein J. Org. Chem. 2019, 15, 1612-
1704; (d) S. M. Roopan, S. M. Patil, J. Palaniraja, Res. Chem.
Intermed. 2016
,
42, 2749-2790; (e) Z. Tashrifi, M.
[17] (a) J.-R. Zhang, Y.-Y. Liao, J.-C. Deng, K.-Y. Feng, M. Zhang,
Y.-Y. Ning, Z.-W. Lin, R.-Y. Tang, Chem. Comunn. 2017, 53,
7784-7787; (b) T. Guo, X.-N. Wei, H.-Y. Wang, Y.-L. Zhu, Y.-
H. Zhao, Y.-C. Ma, Org. Biomol. Chem. 2017, 15, 9455-9464;
(c) T. Guo, X.-N. Wei, M. Zhang, Y. Liu, L.-M. Zhu, Y.-H.
Zhao, Chem. Comunn. 2020, 56, 5751-5754; (d) R. Semwal,
C. Ravi, S. Saxena, S. Adimurthy, J. Org. Chem. 2019, 84,
14151-14160; (e) C. Ravi, N. N. K. Reddy, V. Pappula, S.
Samanta, S. Adimurthy, J. Org. Chem. 2016, 81, 9964-9972;
(f) W. Wu, Y. Ding, P. Xie, Q. Tang, C. U. Pittman, A. Zhou,
Tetrahedron 2017, 73, 2151-2158; (g) F. Xiao, S. Chen, C. Li,
H. Huang, G.-J. Deng, Adv. Synth. Catal. 2016, 358, 3881-
3886; (h) Y.-C. Gao, Z.-B. Huang, L. Xu, Z.-D. Li, Z.-S. Lai,
R.-Y. Tang, Org. Biomol. Chem. 2019, 17, 2279-2286; (i) G.
Xiao, H. Min, Z. Zheng, G. Deng, Y. Liang, Chin. Chem. Lett.
2018, 29, 1363-1366.
[18] C. Ravi, S. Adimurthy, Chem. Rec. 2017, 17, 1019-1038.
[19] (a) X. Lu, Q. Yi, X. Pan, P. Wang, E. Vessally, J. Sulfur Chem.
2020, 41, 210-228; (b) J. Aziz, S. Messaoudi, M. Alami, A.
Hamze, Org. Biomol. Chem. 2014, 12, 9743-9759.
[20] (a) W. Ge, X. Zhu, Y. Wei, Eur. J. Org. Chem. 2013, 6015-
6020; (b) D. C. Mohan, S. N. Rao, C. Ravi, S. Adimurthy,
Asian J. Org. Chem. 2014, 3, 609-613; (c) E. Kianmehr, M.
Ghanbari, M. N. Niri, R. Faramarzi, J. Comb. Chem. 2010, 12,
41-44; (d) R. J. Reddy, A. Shankar, A. H. Kumari, Asian J.
Org. Chem. 2019, 8, 2269-2275; (e) W. Zhu, Y. Ding, Z. Bian,
P. Xie, B. Xu, Q. Tang, W. Wu, A. Zhou, Adv. Synth. Catal.
2017, 359, 2215-2221.
Mohammadi-Khanaposhtani, B. Larijani, M. Mahdavi, Eur. J.
Org. Chem. 2020, 269-284; (f) A. K. Bagdi, A. Hajra, Org.
Biomol. Chem. 2020, 18, 2611-2631.
[3] (a) C. Hamdouchi, J. de Blas, M. del Prado, J. Gruber, B. A.
Heinz, L. Vance, J. Med. Chem. 1999, 42, 50-59; (b) H. Liu,
X. Jiang, Chem. Asian J. 2013, 8, 2546-2563.
[4] (a) Y. Yuan, Y. Cao, J. Qiao, Y. Lin, X. Jiang, Y. Weng, S.
Tang, A. Lei, Chin. J. Chem. 2019, 37, 49-52; (b) H. Iida, R.
Demizu, R. Ohkado, J. Org. Chem. 2018, 83, 12291-12296;
(c) R. Rahaman, S. Das, P. Barman, Green Chem. 2018, 20,
141-147; (d) C. Ravi, D. Chandra Mohan, S. Adimurthy, Org.
Lett. 2014, 16, 2978-2981; (e) Y. Siddaraju, K. R. Prabhu, J.
Org. Chem. 2016, 81, 7838-7846; (f) C. Hamdouchi, C.
Sanchez, J. Ezquerra, Synthesis 1998, 1998, 867-872; (g) Z.
Zheng, D. Qi, L. Shi, Catal. Commun. 2015, 66, 83-86.
[5] (a) J. Rafique, S. Saba, A. R. Rosário, A. L. Braga, Chem.
Eur. J. 2016, 22, 11854-11862; (b) X.-M. Ji, S.-J. Zhou, F.
Chen, X.-G. Zhang, R.-Y. Tang, Synthesis 2015, 47, 659-671;
(c) Z. Gao, X. Zhu, R. Zhang, RSC Adv. 2014, 4, 19891-
19895; (d) Z. Li, J. Hong, X. Zhou, Tetrahedron 2011, 67,
3690-3697; (e) J. Rafique, S. Saba, M. S. Franco, L. Bettanin,
A. R. Schneider, L. T. Silva, A. L. Braga, Chem. Eur. J. 2018
24, 4173-4180.
[6] A. K. Bagdi, S. Mitra, M. Ghosh, A. Hajra, Org. Biomol. Chem.
2015, 13, 3314-3320.
[7] (a) M. A. E. Al-Saedy, J. P. A. Harrity, Synlett 2020, 31, 1182-
,
1184; (b) M. Wang, Y. Li, X. Jiang, Aldrichimica Acta 2020
,
53, 19-25.
[21] (a) K. Pandey, P. Kaswan, A. Kumar, ChemistrySelect 2016
,
[8] (a) C. Ravi, D. Chandra Mohan, S. Adimurthy, Org. Biomol.
Chem. 2016, 14, 2282-2290; (b) D. Wang, S. Guo, R. Zhang,
S. Lin, Z. Yan, RSC Adv. 2016, 6, 54377-54381.
[9] (a) Y.-J. Guo, S. Lu, L.-L. Tian, E.-L. Huang, X.-Q. Hao, X.
Zhu, T. Shao, M.-P. Song, J. Org. Chem. 2018, 83, 338-349;
(b) Y. Ding, W. Wu, W. Zhao, Y. Li, P. Xie, Y. Huang, Y. Liu,
A. Zhou, Org. Biomol. Chem. 2016, 14, 1428-1431; (c) X.
1, 6669-6672; (b) K. Pandey, V. N. Shinde, K. Rangan, A.
Kumar, Tetrahedron 2020, 76, 131499; (c) Saroj, O. P. S.
Patel, K. Rangan, A. Kumar, Tetrahedron Lett. 2019, 60,
150939.
[22] C. D. Prasad, M. Sattar, S. Kumar, Org. Lett. 2017, 19, 774-
777.
[23] (a) Y.-m. Lin, G.-p. Lu, C. Cai, W.-b. Yi, Org. Lett. 2015, 17,
3310-3313; (b) Y. Gao, Y. Gao, X. Tang, J. Peng, M. Hu, W.
Wu, H. Jiang, Org. Lett. 2016, 18, 1158-1161.
Huang, S. Wang, B. Li, X. Wang, Z. Ge, R. Li, RSC Adv. 2015
,
5, 22654-22657.
[10] P. Sun, D. Yang, W. Wei, M. Jiang, Z. Wang, L. Zhang, H.
Zhang, Z. Zhang, Y. Wang, H. Wang, Green Chem. 2017, 19,
4785-4791.
[11] J. Jiao, L. Wei, X. M. Ji, M. L. Hu, R. Y. Tang, Adv. Synth.
Catal. 2016, 358, 268-275.
[24] L. K. Liu, Y. Chi, K.-Y. Jen, J. Org. Chem. 1980, 45, 406-410.
[25] (a) G. Yong, X. Zhang, Y. Zhao, W. She, Chem. Asian J.
2013, 8, 2182-2188; (b) R. A. Abramovitch, D. H. Hey, J.
Chem. Soc. C 1966, 1095-1095.
[12] R. J. Bochis, L. E. Olen, M. H. Fisher, R. A. Reamer, G. Wilks,
J. E. Taylor, G. Olson, J. Med. Chem. 1981, 24, 1483-1487.
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000996
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
Key Topic: Sulfenylation
Synthesis of 3-(arylthio)imidazo[1,2-a]pyridin-2-ols has been achieved via a catalyst-free, one-pot reaction of 2-aminopyridinium
bromides with sodium arenesulfinates. The tandem reaction involved intramolecular amidation followed by sulfenylation and afforded
a wide range of 3-(arylthio)imidazo[1,2-a]pyridin-2-ols in moderate to excellent (33-85%) yields. The method exhibited broad substrate
scope with a wide range of functional group tolerance, and is amenable for gram‐scale synthesis.
8
This article is protected by copyright. All rights reserved.