Iodine-Mediated Sulfenylation of Imidazo[1,2- a ]pyridines with Ethyl Arylsulfinates

Article abstract of DOI:10.1055/a-1396-5933

A simple iodine-mediated approach is reported for the synthesis of sulfenylated imidazo[1,2- a ]pyridines through the reaction of imidazo[1,2- a ]pyridines with ethyl arylsulfinates under mild conditions. The reaction scope was investigated, and a plausible mechanism is proposed to elucidate the reaction process and activation mode. The results indicate that ethyl sulfinates are efficient sulfur sources for the construction of C-S bonds.

Full text of DOI:10.1055/a-1396-5933

SYNLETT
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 32, A–E
letter
A
en
J. Sun et al.
Letter
Synlett
Iodine-Mediated Sulfenylation of Imidazo[1,2-a]pyridines with
Ethyl Arylsulfinates
Jian Suna
Yangxiu Mua
Zafar Iqbala
N
N
I2 (0.75 equiv)
Ar2
Ar1 SO2Et
+
Ar2
N
N
R
MeCN, 120 °C, 8 h
R
H
SAr1
Jing Houa
23 examples
moderate to high yield
Minghua Yangb
Zhixiang Yanga
Dong Tang*a,b
a Ningxia Center of Agricultural Organic Synthesis, Agricultural
Resource and Environment Institute of Ningxia Academy of
Agriculture and Forestry Science, Yinchuan, 750002,
P. R. of China
tangdongabcd@126.com
b Department of Chemistry, Lishui University, Lishui, 323000,
P. R. of China
Corresponding Author
Received: 19.12.2020
Accepted after revision: 20.02.2021
Published online: 20.02.2021
azo[1,2-a]pyridines (Table 1). Alternatively, Guo et al. re-
ported a synthesis of sulfone-substituted imidazo[1,2-
a]pyridines by treatment with sodium sulfinates13 and 1,4-
diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DAB-
DOI: 10.1055/a-1396-5933; Art ID: st-2020-l0635-l
Abstract A simple iodine-mediated approach is reported for the syn-
thesis of sulfenylated imidazo[1,2-a]pyridines through the reaction of
imidazo[1,2-a]pyridines with ethyl arylsulfinates under mild conditions.
The reaction scope was investigated, and a plausible mechanism is pro-
posed to elucidate the reaction process and activation mode. The re-
sults indicate that ethyl sulfinates are efficient sulfur sources for the
construction of C–S bonds.
Table 1 Sulfur Sources for Sulfenylation of Imidazo[1,2-a]pyridines
N
N
reagents and conditions
R1
R2
R1
R2
N
N
SR3/SO2R3
H
Key words iodine, ethyl arylsulfinates, sulfenylation, imidazopyri-
dines, arylsulfenylation
Substitu- Reagent
ents
Conditions
[Ref.]
4
5
6
SR3
R3SO2Na
I2 (1.0 equiv), PPh3(2 equiv), 80 °C, DMF
H2O,140 °C, N2
R3SO2NHNH2
R3SO2Cl
Sulfur-containing aromatics and heteroaromatics form
a considerable proportion of active compounds among ex-
isting natural products; they are also widely used in phar-
maceutical formulations and materials science applica-
tions,1 and as precursors of diverse architectures.2 General-
ly, the bioactivities and properties of organic molecules
depend on the types of substituent groups as well as the
core skeleton. The sulfenylation of heteroarenes through
substitution reactions is an efficient method for the con-
struction of C–S bonds. Imidazo[1,2-a]pyridines are im-
portant scaffolds found in natural products3 and in pharma-
ceuticals such as zolimidine, alpindem, necopidem, and
miroprofen.4 Consequently, the synthesis of sulfenylated
imidazo[1,2-a]pyridine molecules has attracted much at-
tention. Over the years, many sulfenylating agents such as
sodium sulfinates,5 sulfonyl hydrazides,6 sulfenyl chlo-
rides,7 sulfinic acids,8 thiols,9 disulfides,10 S-phenyl sul-
fonothioates,11 and sulfur,12 have been employed for sulfe-
nylation of imidazo[1,2-a]pyridines by C–H bond-activation
strategies, and these transformations provide efficient syn-
thetic tools for the formation of C-3 substituted imid-
CuI (10 mol%), PPh3(3.0 equiv), 130 °C,
toluene
7
8
R3SO2H
R3SH
eosin B (1 mol%), TBHP (0.8 equiv), 3 W
LED, DCE
rose bengal (5 mol%), blue LED, 4Å MS,
DMSO
graphene oxide, H2O, 40 °C
NCS (1.5 equiv), CH2Cl2
5a·TfO (2 mol%), I2 (4 mol%), MeCN
I2 (5 mol%), DMSO, 90 °C
9
R3SSR3
NBS (2 equiv), –10 °C, DMF
NH4I (10 mol%), AcOH (1 equiv), 110 °C,
DMSO–H2O
10
11
R3S–SO2R4
H2O, 120 °C
R3X [X=I, Br,
IPh, I(OAc)2]
S8 (3 equiv), CuI (20 mol%), Na2CO3 (4
equiv), 130 °C, DMF
12
13
SO2R3
R3SO2Na
I2 (1.5 equiv), Na2CO3 (1.5 equiv), 100 °C,
Et2O
R3I
DABSO (1.5 equiv), Cu2O (10 mol%), 130
°C, DMF
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
J. Sun et al.
Letter
Synlett
SO) as the sulfur sources.14 Although these protocols repre-
sent considerable advances in the preparation of C3-sulfe-
nylated imidazo[1,2-a]pyridines, opportunities remain for
the design of methods involving more accessible materials
and routines.
[1a (1 mmol), 2a (1 mmol), I2 (0.75 mmol), MeCN (2 mL),
120 °C], we found that 2a was not completely consumed,
despite prolonging the reaction time to 24 hours. Increasing
the amount of 1a to 2.0 equivalents raised the yield of the
desired product 3aa to 72% (entry 15), with complete con-
sumption of 2a, as observed by liquid chromatogra-
phy/mass spectrometry (LC/MS) analysis.
Sulfenylation of imidazo[1,2-a]pyridines by using the
sulfenylating agents discussed above is performed by using
a variety of additives, catalysts, and reaction conditions.
Despite these significant advances, the development of
more useful building blocks in organic transformations to
construct C–S bonds is still attractive, and sulfinic esters are
also alternative reagents for the introduction of sulfur func-
tional groups in organic synthesis. For instance, a series of
sulfonamides15 and sulfoxides16 have been prepared by us-
ing sulfinic esters; however, alkyl sulfinates have not been
explored for the C3-sulfenylation of imidazo[1,2-a]pyri-
dines. Here, we report an iodine-mediated selective sulfe-
nylation of imidazo[1,2-a]pyridines with ethyl arylsulfi-
nates.
Table 2 Optimization of the Reaction Conditionsa
N
catalyst
SO2Et
N
solvent
N
+
N
S
1a
2a
3aa
Entry Catalyst
Solvent
Temp (°C) Yieldb (%)
1
2
–
EtOH
DMSO
DCE
90
rt
0
NH2NH2.H2O
PPA
0
3
rt
0
To identify the best reaction conditions, ethyl 4-methyl-
benzenesulfinate (1a) and 2-phenylimidazo[1,2-a]pyridine
(2a) were initially used as the model reactants (Table 2).
The reported method for catalyst-free sulfenylation of in-
doles in ethanol with sulfinic esters17 was unsuccessful in
our case, and the use of hydrazine hydrate18 as a reducing
agent did not improve the situation (Table 2, entries 1 and
2). A further survey of the literature revealed that anhy-
drides are efficient reagents19 for the deoxygenation of aryl
sulfoxides to the corresponding sulfides. We therefore test-
ed various anhydrides, including trifluoromethanesulfonic
anhydride (Tf2O), polyphosphoric acid (PPA), trifluoroacetic
anhydride (TFAA), and acetic anhydride (Ac2O), in dichlo-
roethane (DCE) at room temperature for eight hours (en-
tries 3–6). Whereas the other anhydrides failed to initiate
the reaction, Tf2O gave the desired product 3aa in 27% yield.
Increasing the temperature to 60 °C (entry 7) reduced the
yield to 19%, indicating degradation of reaction compo-
nents. We therefore discarded the idea of using an anhy-
dride and began to explore other reagents. A combination
of iodine and an oxidizing agent has been successfully em-
ployed for sulfenylation reactions with sulfinic esters as
sulfur sources.20 When we heated reactants 1a and 2a to
120 °C in acetonitrile in the presence of I2 and di-tert-butyl
peroxide (DTBP), 3aa was obtained in 34% yield (entry 8).
We later observed that an oxidizing agent is not necessary
for this conversion, and a higher yield of 41% was obtained
by increasing the molar ratio of I2 from 10 mol% to 0.5
equivalents (entry 9). With this combination of reaction
conditions, we screened various solvents [DMSO, dichlo-
roethane (DCE), 1,4-dioxane, and toluene] and found that
that MeCN was the best one (entries 10–13). In an attempt
at further improvement, the molar ratio of iodine was in-
creased to 0.75 equivalents, and 51% of the desired product
3a was isolated (entry 14). Under these reaction conditions
4
Ac2O
DCE
rt
0
5
TFFA
DCE
rt
trace
27
19
34
41
27
35
trace
trace
51
72
6
Tf2O
DCE
rt
7
Tf2O
DCE
60
8
I2 (10 mol%) + DTBP (3 equiv) MeCN
120
120
120
120
120
120
120
120
9
I2 (0.5 equiv)
I2 (0.5 equiv)
I2 (0.5 equiv)
I2 (0.5 equiv)
I2 (0.5 equiv)
I2 (0.75 equiv)
I2 (0.75 equiv)
MeCN
10
11
12
13
14
15c
toluene
DCE
1,4-dioxane
DMSO
MeCN
MeCN
a Reaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), solvent (2 mL), 8 h.
b Isolated yield based on 2a.
c 1a (2 equiv).
With the optimized reaction conditions in hand (Table
2, entry 15), we investigated the substrate scope and limita-
tions of ethyl arylsulfinates for arylsulfenylation of imidaz-
opyridines. As shown in Table 3, a variety of sulfinic esters
with various substituents, such as halo, methyl (Me), me-
thoxy (OMe), trifluoromethyl (CF3), or tert-butyl (t-Bu)
groups were tested and gave the desired products 3ab−am
in yields of 59–88%. Sulfinates with electron-donating
groups, such as Me and t-Bu, or electron-withdrawing
groups, such as CF3 and Cl, both performed well in this
transformation (Table 3, entries 1, 5, 7, and 12). Moreover,
sulfinic esters with electron-withdrawing substituents in
the ortho-position gave better results than those with a
similar substituent in the meta- or para-position (entries
7–9), suggesting the reaction is not affected by steric hin-
drance. The electronic nature of the aryl group showed an
obvious influence on the outcome. As expected, reactants
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E

C
J. Sun et al.
Letter
Synlett
with bulky groups, such as naphthyl or isobutyl, were well
tolerated affording the desired products 3ae and 3am in
yields of 72 and 59%, respectively (entries 4 and 12).
Table 4 Substrate Scope of Imidazo[1,2-a]pyridines a
N
3
2
Ar
R
4
5
N
SO2Et
I2 0.75 equiv)
N
Ar
R
N
+
S
MeCN, 120 °C, 8 h
Table 3 Substrate Scope of Ethyl Sulfonesa
6
1a
2
3
N
N
I2 (0.75 equiv)
Ph
Ar1 SO2Et
Ph
Entry R1
R2
Ar
Product
Yieldb (%)
+
N
N
MeCN, 120 °C, 8 h
SAr1
1
3
2a
1
2
3-Me
H
Ph
3ba
3ca
3da
3ea
3fa
71
57
64
49
65
73
57
49
66
68
5,6-CH=CH–CH=CH
Ph
Entry
Ar1
Product
Yieldb (%)
3
3-Cl
4-Me
4-Cl
H
H
Ph
1
2
2-MeC6H4
3-MeC6H4
4-MeOC6H4
2-naphthyl
4-F3CC6H4
4-FC6H4
3ab
3ac
3ad
3ae
3af
73
62
84
72
85
70
88
73
65
60
77
59
4
6-Me
H
Ph
5
Ph
3
6
H
4-MeC6H4
4-FC6H4
4-NCC6H4
4-MeOC6H4
4-ClC6H4
3ga
3ha
3ia
4
7
H
H
5
8
H
H
6
3ag
3ah
3ai
9
H
H
3ja
7
2-ClC6H4
3-ClC6H4
4-ClC6H4
4-BrC6H4
4-IC6H4
10
H
H
3ka
8
a Reaction conditions 1a (2.0 equiv), 2 (0.2 mmol), I2 (0.75 equiv), MeCN,
120 °C, 8 h.
9
3aj
b Isolated yield based on 2.
10
11
12
3ak
3al
therefore treated commercially available diphenyl disulfide
(4b) with 2a under optimized reaction conditions and ob-
tained the corresponding product 3an in 56% yield (Scheme
1b).
4-t-BuC6H4
3am
a Reaction conditions: 1 (2.0 equiv), 2a (0.2 mmol), I2 (0.75 equiv), MeCN,
120 °C, 8 h.
b Isolated yield based on 2a.
(a) 1a under the optimized conditions
To further investigate the scope and limitations of this
reaction system, a small range of imidazo[1,2-a]pyridines
were examined under the optimized reaction conditions
(Table 4). Generally, substances with substituents such as
Me, OMe, CN, F, or Cl gave the corresponding products in
moderate to good yields. The electronic nature of substitu-
ents on the pyridine ring had no significant effect in the
transformation (Table 4, entries 1 and 3). An effect of steric
hindrance was obvious in this reaction, and the 4,6-dimeth-
ylated reactant gave the corresponding product 3ea in 49%,
probably due to steric hindrance by the group at the C6-po-
sition (entries 2 and 4). Imidazo[1,2-a]pyridines with sub-
stituents such as Me, F, Cl, CN, or OMe on the Ar2 group re-
acted smoothly under the optimal reaction conditions, pro-
viding the corresponding products in moderate to good
yields (entries 6–7 and 9–10), and only the substrate with a
cyano group gave 3ia in a comparatively lower yield (entry
8). Therefore, electronic and steric effects of substituents on
the imidazo[1,2-a]pyridine are negligible in this protocol.
Next, we performed control experiments to understand
the probable reaction mechanism of this sulfenylation reac-
tion (Scheme 2). When ethyl 4-methylbenzenesulfinate
(1a) reacted with 2a under the optimized reaction condi-
tions (Scheme 1a), the possible intermediate disulfide 4
was observed by LC/MS. This indicates that the disulfide is a
stable key intermediate formed during this process. We
SO2Et
S
S
1a
4a
observed by LC-MS
(b) Disulfide 4b reacted with 2a under the optimized conditions
N
N
Ph
Ph
Ph
PhSSPh
+
N
N
S
4b
2a
3an
56%
Scheme 1 Primary mechanistic studies
Based on this experimental evidence and previous re-
ports on similar transformations,16b,19 a plausible mecha-
nism is proposed in Scheme 2. Initially ethyl sulfinate 1 re-
acts with iodine to generate a radical complex A, where io-
dine might act as a Lewis acid.16a,20,21 Complex A dimerizes
to form intermediate B through a free-radical reaction, fol-
lowed by reductive elimination of acetaldehyde and hydro-
gen peroxide to give disulfide C.18 The byproducts are fur-
ther transformed into acetic acid and water. Subsequent ox-
idation of intermediate C in the presence of iodine
generates intermediate D,13 which is converted into inter-
mediate E through regioselective electrophilic attack by
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E

D
J. Sun et al.
Letter
Synlett
(2) (a) Wang, L.; He, W.; Yu, Z. Chem. Soc. Rev. 2013, 42, 599.
(b) Modha, S. G.; Mehta, V. P.; Van der Eycken, E. V. Chem. Soc.
Rev. 2013, 42, 5042.
(3) (a) DiMauro, E. F.; Kennedy, J. M. J. Org. Chem. 2007, 72, 1013.
(b) Enguehard-Gueiffier, C.; Gueiffier, A. Mini-Rev. Med. Chem.
2007, 7, 888.
[I]
[I]
O
S
O
S
O
S
O
S
I2
Ar1S SAr1
Ar1
Ar1
Ar1
OEt
Ar1
OEt
OEt OEt
C
MeCHO, H2O2
I2
1
A
B
Ar1S
I
D
MeCOOH, H2O
(4) (a) Okubo, T.; Yoshikawa, R.; Chaki, S.; Okuyama, S.; Nakazato,
A. Bioorg. Med. Chem. 2004, 12, 423. (b) Ilardi, E. A.; Vitaku, E.;
Njardarson, J. T. J. Med. Chem. 2014, 57, 2832. (c) Ritchie, T. J.;
Macdonald, S. J. J. Med. Chem. 2014, 57, 7206. (d) Kucher, O. V.;
Kolodyazhnaya, A. O.; Smolii, O. B.; Nazarenko, N. K.; Kubyshkin,
V. P.; Mykhailiuk, K.; Tolmachev, A. A. Tetrahedron: Asymmetry
2016, 27, 341.
N
Ar2
N
R
2
HI
N
Ar2
N
Ar2
N
N
I
R
SAr1
H
R
SAr1
(5) Huang, X.; Wang, S.; Li, B.; Wang, X.; Ge, Z.; Li, R. RSC Adv. 2015,
5, 22654.
3
E
Scheme 2 Proposed mechanism
(6) Chowdhury, S. R.; Fadikar, P.; Ul Hoque, I.; Maity, S. Asian J. Org.
Chem. 2018, 7, 332.
(7) Ravi, C.; Mohan, D. C.; Adimurthy, S. Org. Biomol. Chem. 2016,
14, 2282.
substrate 2. The desired product 3 is formed by elimination
of HI from intermediate E.
(8) Sun, P.; Yang, D.; Wei, W.; Jiang, M.; Wang, Z.; Zhang, L.; Zhang,
H.; Zhang, Z.; Wang, Y.; Wang, H. Green Chem. 2017, 19, 4785.
(9) (a) Ravi, C.; Chandra Mohan, D.; Adimurthy, S. Org. Lett. 2014,
16, 2978. (b) Rahaman, R.; Das, S.; Barman, P. Green Chem. 2018,
20, 141. (c) Iida, H.; Demizu, R.; Ohkado, R. J. Org. Chem. 2018,
83, 12291.
(10) (a) Ge, W.; Zhu, X.; Wei, Y. Eur. J. Org. Chem. 2013, 2013, 6015.
(b) Rafique, J.; Saba, S.; Rosário, A. R.; Braga, A. L. Chem. Eur. J.
2016, 22, 11854. (c) Maddi, R. R.; Shirsat, P. K.; Kumar, S.;
Meshram, H. M. ChemistrySelect 2017, 2, 1544. (d) Bettanin, L.;
Saba, S.; Doerner, C. V.; Franco, M. S.; Godoi, M.; Rafique, J.;
Braga, A. L. Tetrahedron 2018, 74, 3971.
In summary, we have developed an efficient iodine-me-
diated sulfenylation of imidazo[1,2-a]pyridines in which an
ethyl sulfinate is used as an alternative sulfur source for the
construction of a C–S bond.22 This protocol provides a con-
venient method for accessing sulfenylated compounds in
generally moderate to good yields.
Conflict of Interest
(11) (a) Ravi, C.; Joshi, A.; Adimurthy, S. Eur. J. Org. Chem. 2017, 2017,
3646. (b) Reddy, R. J.; Shankar, A.; Kumari, A. H. Asian J. Org.
Chem. 2019, 8, 2269.
The authors declare no conflict of interest.
(12) (a) Zhu, W.; Ding, Y.; Bian, Z.; Xie, P.; Xu, B.; Tang, Q.; Wu, W.;
Zhou, A. Adv. Synth. Catal. 2017, 359, 2215. (b) Ravi, C.; Reddy, N.
N. K.; Pappula, V.; Samanta, S.; Adimurthy, S. J. Org. Chem. 2017,
81, 9964.
(13) Guo, Y.-J.; Lu, S.; Tian, L.-L.; Huang, E.-L.; Hao, X.-Q.; Zhu, X.;
Shao, T.; Song, M.-P. J. Org. Chem. 2018, 83, 338.
Funding Information
We gratefully acknowledge financial support from the Ningxia Key
Research and Development Program (2018BEB04034) and the Natural
Science Foundation of Zhejiang Province, P. R. of China
(LY18B020004).Natural
S
cienceFo
u
n
dati
o
n
o
f
Z
hejia
n
g
Pro
v
ince(LY
1
8
B
0
2
0
0
0
4)K
e
y
Researchan
d
D
e
velo
p
me
n
t
Program
o
f
Nin
g
x
ia(2
0
1
8
B
E
B
0
4
0
3
4)
(14) Yang, D.; Sun, P.; Wei, W.; Liu, F.; Zhang, H.; Wang, H. Chem. Eur.
J. 2018, 24, 4423.
Supporting Information
(15) (a) Li, G.-J.; Pan, Y.-L.; Liu, Y.-L.; Xu, H.-F.; Chen, J.-Z. Tetrahedron
Lett. 2019, 60, 151260. (b) Ruano, J. L. G.; Parra, A.; Yuste, F.;
Mastranzo, V. M. Synthesis 2008, 2008, 311. (c) Ruano, J. L. G.;
Parra, A.; Marzo, L.; Yuste, F.; Mastranzo, V. M. Tetrahedron
2011, 67, 2905.
Supporting information for this article is available online at
https://doi.org/10.1055/a-1396-5933. Su
p
p
ortingInformatio
n
Su
p
p
ortingInformatio
n
(16) (a) Yuste, F.; Hernández Linares, A.; Mastranzo, V. M.; Ortiz, B.;
Sánchez-Obregón, R.; Fraile, A.; Garcia Ruano, J. L. J. Org. Chem.
2011, 76, 4635. (b) Ni, C.; Zhang, L.; Hu, J. J. Org. Chem. 2009, 74,
3767.
(17) (a) Li, J.; Chen, Y.; Zhong, R.; Zhang, Y.; Yang, J.; Ding, H.; Wang,
Z. Org. Lett. 2020, 22, 1164. (b) Bahrami, K.; Khodaei, M. M.;
Karimi, A. Synthesis 2008, 2008, 2543. (c) Meng, X.; Chen, D.;
Cao, X.; Luo, J.; Wang, F.; Huang, S. Chem. Commun. 2019, 55,
12495.
References and Notes
(1) (a) Zhao, Z.; Pissarnitski, D. A.; Josien, H. B.; Wu, W.-L.; Xu, R.; Li,
H.; Clader, J. W.; Burnett, D. A.; Terracina, G.; Hyde, L.; Lee, J.;
Song, L.; Zhang, L.; Parker, E. M. J. Med. Chem. 2015, 58, 8806.
(b) Feng, M.; Tang, B.; Liang, S. H.; Jiang, X. Curr. Top. Med. Chem.
(Sharjah, United Arab Emirates) 2016, 16, 1200. (c) Kang, D.;
Fang, Z.; Huang, B.; Lu, X.; Zhang, H.; Xu, H.; Huo, Z.; Zhou, Z.;
Yu, Z.; Meng, Q.; Wu, G.; Ding, X.; Tian, Y.; Daelemans, D.; De
Clercq, E.; Pannecouque, C.; Zhan, P.; Liu, X. J. Med. Chem. 2017,
60, 4424. (d) Mao, Z.; Yang, Z.; Mu, Y.; Zhang, Y.; Wang, Y.-F.;
Chi, Z.; Lo, C.-C.; Liu, S.; Lien, A.; Xu, J. Angew. Chem. Int. Ed.
2015, 54, 6270. (e) Zhang, C.; Zhu, X. Acc. Chem. Res. 2017, 50,
1342.
(18) Yang, X.; Bao, Y.; Dai, Z.; Zhou, Q.; Yang, F. Green Chem. 2018, 20,
3727.
(19) Zhu, R.-H.; Shi, X.-X. Synth. Commun. 2012, 42, 1108.
(20) Li, Y.; Zhu, F.; Wang, Z.; Wu, X.-F. Chem. Asian J. 2016, 11, 3503.
(21) (a) Ji, Y.-Z.; Li, H.-J.; Wang, Y.-R.; Zhang, Z.-Y.; Wu, Y.-C. Adv.
Synth. Catal. 2020, 362, 1039. (b) Nguyen, N.-L. T.; Vo, H.-T.;
Duus, F.; Luu, T. X. T. Molecules 2017, 22, 1458.
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(22) 3-(Arylsulfanyl)imidazo[1,2-a]pyridines 3aa–am and 3ba–
ka; General Procedure
3-[(4-Methylphenyl)sulfanyl]-2-phenylimidazo[1,2-a]pyri-
dine (3aa)
A sealed tube was charged with the appropriate ethyl arylsulfi-
nate (0.4 mmol), imidazo[1,2-a]pyridine (0.2 mmol), I2 (0.75
equiv), and MeCN (2 mL), and the mixture was stirred at 120 °C
for 6 h. When the reaction was complete, the mixture was
allowed to cool to r.t. and concentrated under reduced pressure.
The residue was purified by chromatography (silica gel, 10%
EtOAc–PE).
Yellow solid; yield: 45 mg (72%); mp 131–133 °C. 1H NMR (400
MHz, CDCl3):  = 8.30 – 8.14 (m, 3 H), 7.72 (d, J = 9.0 Hz, 1 H),
7.49–7.25 (m, 4 H), 7.01 (d, J = 8.0 Hz, 2 H), 6.95–6.78 (m, 3 H),
2.24 (s, 3 H). 13C NMR (101 MHz, CDCl3):  = 151.21, 147.04,
136.05, 133.42, 131.51, 130.23, 128.58, 128.43, 128.41, 126.61,
125.84, 124.55, 117.64, 113.04, 106.89, 20.91. HRMS (ESI): m/z
[M + H]+ calcd for C20H17N2S: 317.1107; found: 317.1105.
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E