Temperature-Controlled Chalcogenation and Chalcogenocyanation of Imidazopyridines in Water under Transition Metal-Free Conditions

Article abstract of DOI:10.1021/acs.joc.0c01035

A sustainable and transition metal-free approach for C3 chalcogenation and chalcogenocyanation of imidazopyridines with KXCN (X = S or Se) has been developed under mild conditions. Importantly, this reaction was performed in the presence of catalytic iodi

Full text of DOI:10.1021/acs.joc.0c01035

Subscriber access provided by Uppsala universitetsbibliotek
Article
Temperature-controlled chalcogenation and chalcogenocyanation
of imidazopyridines in water under transition-metal-free conditions
Yu-Shen Zhu, Yuting Xue, Wannian Liu, Xinju Zhu, Xin-Qi Hao, and Mao-Ping Song
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01035 • Publication Date (Web): 16 Jun 2020
Downloaded from pubs.acs.org on June 16, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 13
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Temperature-controlled chalcogenation and chalcogenocyanation
of imidazopyridines in water under transition-metal-free
conditions
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Yu-Shen Zhu, Yuting Xue, Wannian Liu, Xinju Zhu, Xin-Qi Hao* and Mao-Ping Song*
College of Chemistry, Zhengzhou University, No. 100 of Science Road, Zhengzhou, Henan 450001, P. R. China
Email: xqhao@zzu.edu.cn (X.Z); mpsong@zzu.edu.cn (M.P.S)
N
N
KX CN
X
110°C
N
N
I2, PIDA
N
N
H2O
N
H
KXCN
rt
N
X=Se, S
XCN
transition-metal-free
organic solvent-free
temperature control



operational convenience
broad substrate scope
gram-sacle production



ABSTRACT: A sustainable and transition-metal-free approach for C3 chalcogenation and chalcogenocyanation of
imidazopyridines with KXCN (X = S or Se) has been developed under mild conditions. Importantly, this reaction was
performed in the presence of catalytic iodine in aqueous medium, which afforded either chalcogenated or
chalcogenocyanated imidazopyridines under temperature control. The current protocol featured broad substrate scope,
transition-metal- and organic solvent-free, operational convenience, and gram-scale production.
preparation and functionalization of imidazopyridines
INTRODUCTION
have received much attention.12 Meanwhile, C-H
Organochalcogenides have been recognized as essential
structural moieties prevalence in various natural products,
pharmaceuticals, and materials science.1 Meanwhile,
chalcogen functionalities play an important role in
chalcogenation of imidazopyridines with elemental
chalcogen, dichalcogenides, chalcogenosulfonates, and
other reagents has also been investigated (Scheme 1a).13
Recently, thiocyanation of imidazopyridines with KSCN,
NH4SCN, and NaSCN has
organic
synthesis
and
catalytic
applications.2
Consequently, considerable efforts have been made to
efficient access organochalcogen compounds in the
presence of various chalcogen sources.3,4 Among these
regents, chalcogenocyanate salts stand out due to their
commercial availability, odorless, and stability, which has
been proved to be efficient and versatile reagents for the
preparation of pharmaceutically important and bioactive
organic chalcogenocyanates enabled for further
transformations.5 Until now, thiocyanation of alkenes,6
alkynes,7 (hetero)aromatics,8 and ketones9 has been
successfully achieved. Nevertheless, protocols for efficient
synthesis of organoselenocyanates remain to be
developed.10
Scheme 1. C–S/Se bond formation of imidazopyridines
Imidazo[1,2-a]pyridine moiety is an important class of
N-heterocycles with wide applications in medicinal
chemistry, materials science, and catalysis.11 Considering
the importance of imidazopyridine derivatives,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
were investigated, which all gave inferior results (Table 1,
N
Page 2 of 13
Previous work
X = S, Se
N
X, RXXR, RSO2XR', RSH, RSO2H
1
2
3
4
5
6
7
8
entries 2-5). Next, a series of oxidants were screened
(Table 1, entries 6-9), indicating addition of PIDA (1.0
equiv) was beneficial to provide 2a in 74% yield (Table 1,
entry 6). To further improve reaction efficiency, the molar
ratio of reactants and amount of oxidant was examined,
which gave 2a in up to 97% yield (Table 1, entry 11).
Moreover, product 2a could still be isolated in 99% yield
when the reaction time was shortened to 3 h (Table 1,
entry 12). However, reaction between 1a and KSeCN using
1.5 equiv of PIDA without catalytic amount of I2 or 1.5
equiv of I2 without PIDA both gave lower results (Table 1,
entries 13-14). Finally, the contents of Co, Cr, Cu, Fe, Ru,
Rh, Mn, Pd, Ni, Ir, Pt, and Zn in the reaction mixture were
all < 0.01 ppm (ICP-MS), indicating a transition-metal-
free environment (see the supporting information). The
structure of 2a was further confirmed by X-ray
crystallography analysis (see the supporting information).
(a)
N
N
RSO2NHNH2, RSO2Cl, RSO2Na, etc.
H
XR
N
N
KSCN, NH4SCN, NaSCN
organic solvent
(b)
(c)
N
N
N
H
SCN
N
N
SeO2, malononitrile
N
DMSO
H
SeCN
N
N
9
N
N
N
PhNCS
DMF
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(d)
S
N
H
This work
X = S, Se
N
N
N
N
N
N
KXCN, 110 o
C
KXCN, r.t.
X
(e)
N
N
H2O
H2O
XCN
H
been developed under transition-metal-free or photo
irradiation conditions (Scheme However,
1b).14
Table 1. Optimization of reaction conditionsa
selenocyanated imidazopyridines was only prepared by
Vanelle and co-workers using combination of SeO2 and
malononitrile as the selenocyano source (Scheme 1c).15 To
the best of our knowledge, employment of
chalcogenocyanate salts as both chalcogenating and
chalcogenocyanating reagents via C-H activation has not
been realized. Meanwhile, challenges still remain for
development of green and sustainable preparation of
functionalized imidazopyridines.
N
I2 (20 mol%)
oxidant
solvent, 110 oC, 12 h
N
N
N
+
KSeCN
Se
N
H
N
1a
2a
(0.2 mmol)
Entry
oxidant (eq)
solvent
H2O
yield (%)
40
23
1
-
Facing the challenge of environmental issues and
depletion of non-renewable resources, water has become
an alternative reaction medium compared with
traditional organic solvents due to its nature abundance,
easy acquisition, low cost, and environmentally benignity
properties.16 Meanwhile, compared with transition-
metals, molecular iodine has also emerged as a powerful
catalyst in organic synthesis.17 In accordance with
principles of green chemistry, we have recently developed
C-H sufonylmethylation of imidazopyridines and indoles
in nontoxic media.18a We also have reported iodine-
mediated C-H sulfonylation and sulfenylation of
imidazopyridines and indolines.18b,c Very recently, copper-
catalyzed synthesis of sulfur-bridged imidazopyridines
has also been successfully achieved (Scheme 1d).18d As the
continuation of our experience in C-H functionalization
of imidazopyridines,18,19 we herein develop temperature-
dependent chalcogenation and chalcogenocyanation of
imidazopyridines with KSCN and KSeCN (Scheme 1e).
Specially, this methodology was performed in water
under transition-metal-free conditions, which is more
operationally convenient and environmentally friendly.
2
3
4
5
6
7
8
9
-
DMF
DMSO
CH3CN
DCE
H2O
-
32
-
27
-
28
PIDA (1.0)
K2S2O8 (1.0)
DTBP (1.0)
TBHP (1.0)
PIDA (1.0)
PIDA (1.5)
PIDA (1.5)
PIDA (1.5)
-
74
H2O
11
H2O
36
H2O
48
78
10b
11b
H2O
H2O
97
12b,c
13b,c,d
14b,c,e
H2O
99
65
H2O
H2O
21
RESULTS AND DISCUSSION
aReaction Conditions: 1a (0.2 mmol), KSeCN (0.3 mmol), I2 (20 mol
%), oxidant (equiv), solvent (1 mL), under air, 110 oC, 12 h. Isolated
yields. KSeCN (0.2 mmol). 3 h. Without I2. I2 (1.5 equiv). PIDA =
(Diacetoxyiodo)benzene.
We initiated our studies with 2-phenylimidazo[1,2-
α]pyridine 1a (0.2 mmol) and KSeCN (0.3 mmol) in the
presence of I2 (20 mol%) in water (1 mL). To our delight,
selenium-bridged product 2a was obtained in 40% yield
at 110 °C for 12 h under air (Table 1, entry 1). Subsequently,
various solvents, such as DMF, DMSO, CH3CN, and DCE,
b
c
d
e
With the optimized conditions in hand (Table 1, entry
12), the substrate scope of imidazopyridines was
investigated using KSeCN as the seleno source (Table 2).
2
ACS Paragon Plus Environment

Page 3 of 13
1
The Journal of Organic Chemistry
N
N
Initially, para, meta, and ortho- substituted 2-
phenylimidazo[1,2-α]pyridines were employed, affording
I2 (20 mol %)
PIDA (1.5 equiv)
H2O (1 mL), 110 o
R1
R1
N
N
N
R2
R2
R1
KXCN
+
X
N
R2
C
2
3
4
5
6
7
8
9
the corresponding products 2a-i in 32-99% yields. When
Br substituent was introduced at the ortho position, only
selenium-bridged product 2i was obtained instead of
benzo[b]selenophene-fused derivative.20 Subsequently,
both electron-donating (OCH3 and CH3) and electron-
withdrawing groups (Cl, Br, and COOCH3) on the various
positions of pyridine ring were also examined, which
provided products 2j-s in 59-93% yields. Meanwhile,
H
1
2 or 3
R2
R2
X = Se, 3 h
N
N
N
N
N
N
R2
R2
N
Se
Se
Se
N
N
N
N
N
R2
R2
imidazoheterocycle
substrates
phenylimidazo[2,1-b]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
, R2 = H, 99%
, R2 = CH3, 45%
, R2 = Cl, 98%b
, R2 = OCH3, 61%
2a
2e
2f
2g
2h
2i
, R2 = OCH3, 45%
2
, R2 = F, 97%
thiazole and 2,3-dihydroimidazo[2,1-b]thiazole were also
well tolerated to give products 2t and 2u in 76% and 86%
yield. Next, imidazo[1,2-a]pyridine bearing various
substituents, including furanyl, thienyl, Me, H, and
COOEt, on the C2 position of imidazole ring were
evaluated, furnishing the desired products 2v-z in 31-84%
yields. Finally, other electron-rich aromatics were also
explored to test the generality of current protocol.
2b
2c
2d
tBu, 96%
, R2 = Br, 32%
R1
, R
=
, R2 = Cl, 54%
N
R1
Ph
N
N
S
N
N
N
Ph
Ph
Ph
Ph
Ph
N
N
Se
N
N
N
N
R1
Se
Se
Se
R1
Ph
N
Ph
R1
R1
S
N
N
N
, R1 = OCH3, 87%
, R1 = Cl, 77%
, R1 = Br, 93%
, R1 = CH3, 70%b
, R1 = OCH3, 59%b
, R1 = CH3, 78%
b
2j
2m
2n
2p
2q
2r
2t
, 76%
, R1 = Cl, 73%b
, R1 = Br, 87%
2k
2l
, R1 = Cl, 86%
2o
, R1 = COOCH3, 72%
2s
Table 2. Substrate scope of imidazopyridinesa
S
S
N
N
N
N
N
Ph
Ph
CH3
N
N
N
N
Y
Se
Se
Se
Se
Y
N
N
N
N
CH3
N
N
N
b
b
b
2x
, 70%
2u
2v
2y
, 84%
, 86%
, Y = O, 45%
b
2w
, Y = S, 68%
N(CH3)2
O
N
Se
OCH3
N
N
OEt
OEt
O
SeCN
Se
H3CO
OCH3
N
N(CH3)2
2aa
N
SeCN
c
2z
2ab
2ac
, 31%
, 44%
, 53%
, 41%
F
Cl
X = S, 12 h
N
N
N
N
N
N
N
N
N
R2
R2
S
S
S
N
N
N
Cl
Cl
F
, R2 = H, 86%, 94%d, 95%e
2
3c
3d
, 96%
, 97%
3a
3b
, R
=
tBu, 97%
N
Ph
Br
N
N
N
S
N
N
N
Ph
Ph
Ph
Ph
S
N
N
N
R1
R1
S
S
N
S
Ph
N
N
N
N
Ph
Ph
N
Cl
3h
S
Br
, R1 = F, 77%
, R1 = OMe, 79%
, 87%, 98%
e
e
3i
, 84%
3e
3f
3g
, 77%, 92%
aReaction Conditions: 1 (0.2 mmol), KXCN (0.2 mmol), I2 (20 mol %),
o
b
c
PIDA (1.5 equiv), H2O (1 mL), 110 C, under air. 12 h. Determined by
1H NMR analysis. dNaSCN, 3 h. eNH4SCN, 12 h.
N,N-dimethylaniline was examined to generate mixture of
selenocyanated (19%) and selenium-bridged21 product
(2aa, 44%), which could not be isolated. For 1,3,5-
trimethoxybenzene
and
N-methyl
indole,
only
selenocyanated products 2ab and 2ac were obtained.
According to previous reports, KSCN, NH4SCN, and
NaSCN were independently utilized as thiocyanating
reagents.14 Surprisingly, reaction between 1a and KSCN at
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 13
o
110 C for 12 h led to formation of sulfur-bridged product
3a in 86% yield.18d In light of this result, various
imidazo[1,2-a]pyridines were test using KSCN as the
sulfur source, which delivered the corresponding
products 3b-i in 77-97% yields. It is also noteworthy that
replacement of KSCN with NH4SCN could further
improve the production of 3a, 3g, and 3h in up to 98%
yield.
which delivered the corresponding products 2a, 3a, 4a,
1
2
3
4
5
6
7
8
and 5a in 80%, 82%, 91%, and 90% yields (Scheme 2).
Scheme 2. Gram-scale production.
N
KXCN (1.5 equiv)
I2 (20 mol %)
PIDA (1.5 equiv)
KXCN (1.0 equiv)
I2 (20 mol %)
PIDA (1.5 equiv)
N
N
N
X
1a
H2O (25 mL), 110 o
C
N
H2O (25 mL), r.t.
XCN
(5 mmol, 0.97 g)
N
d
b
4a
5a
2a
3a
, X = Se, 91%
, X = Se, 80%
As mentioned above, selenocyanated products were
e
c
, X = S, 90%
, X = S, 82%
9
aReaction conditions: 1a (5 mmol), KXCN, I2 (20 mol %), PIDA (1.5
equiv), H2O (25 mL), under air. bKSeCN (5 mmol), 3 h. cKSCN (5
mmol), 12 h. dKSeCN (7.5 mmol), 30 min. eKSCN (7.5 mmol), 12 h.
formed
for
electron-rich
aromatics
such
as
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
trimethoxybenzene and indole. Pleasingly, when reaction
between 1a (0.2 mmol) and KSeCN (0.3 mmol) was
carried out in water at room temperature for 30 min, the
desired selenocyanated imidazopyridine 4a could be
isolated in 92% yield (Table 3). Subsequently, a series of
imidazopyridines bearing either electron-donating groups
or electron-withdrawing groups on both imidazole and
pyridine rings were examined, which provided products
4b-j in 48-97% yields. Next, other electron-rich arenes
were also employed, which gave the corresponding
products 4k-l in 46-88% yields. Finally, KSCN was also
utilized as the thiocy anating reagents to provide the
thiocyanated imidazopyridines 5a-g in 46-92% yields.
To explore the reaction mechanism, a set of control
experiments were conducted (Scheme 3). Firstly, reaction
between 1a and KSeCN was terminated after 10 min,
which produced 2a, 4a, and iodo-substituted
imidazopyridine 6 (Scheme 3, eq 1). When stirred at 110 oC
for 3 h or at room temperature for 30 min, 1a itself could
also give iodide product 6 in 46% or 47% yield (Scheme 3,
eq 2). Meanwhile, reaction of 6 with KSeCN at room
temperature for 30 min would generate 4a in 78% yield,
which could further converted into 2a and 1a in 45% and
o
22% yields, respectively, after heated at 110 C for 3 h.
However, no desired products 4a and 2a could be
detected without I2 and PIDA (Scheme 3, eq 3), which is
Table 3. Substrate scope of imidazopyridinesa
I2 (20 mol %)
accordance
with
previous
sulfenylation
of
N
N
PIDA (1.5 equiv)
H2O (1 mL), r.t.
imidazopyridines with disulfides.21 These results suggest
that selenocyanated product 4a is the intermediate to
selenium-bridged product 2a. Meanwhile, iodide product
6 might not be the intermediate, which could undergo
deiodination back to imidazopyridine 1a. Next, the radical
scavenger reactions were performed (Scheme 3, eq 3 and
4). In eq 3, coupling between 6 and KSeCN in the
+
R1
R1
KXCN
N
R2
N
R2
XCN
H
1
4 or 5
X = Se, 30 min
N
N
N
N
R2
N
N
O
SeCN
SeCN
SeCN
Cl
, R2 = H, 92%
4a
4d,
4e
48%
, 79%
, R2 = Cl, 58%
presence of
1
equiv TEMPO could still give
4b
4c
, R2 = CF3, 79%
selenocyanated product 4a in 69% yield. On the contrary,
only 5% yield of 2a was isolated when 4a itself was heated
under the optimized conditions in the presence of 1 equiv
TEMPO. In eq 4, when 1 equiv TEMPO, BHT, or BQ was
added, formation of 2a was inhibited, indicating that this
reaction might undergo a radical pathway. To further
clarify the proposed mechanism, a crossover experiment
in the presence of two different starting materials 1a and
1z was conducted, which only gave homocoupling
products 2a and 2z in 81% and 34% yields, respectively.
Nevertheless, reaction between 4a and 1z under the
optimized conditions could afford product 7 in 20% yield
(Scheme 3, eq 5). Finally, KOCN was also proved to be
potential potassium salt to furnish oxygen-bridge
imidazopyridine 8 in 19% yield (Scheme 3, eq 6).
OCH3
H3C
N
N
N
S
N
Ph
Ph
Ph
Ph
SeCN
N
N
N
N
R1
SeCN
SeCN
, 95%
SeCN
, R1 = CH3, 97%
, 81%
85%
4f
4h
4i
4j:
, R1 = Br, 49%
4g
OCH3
H3C
SeCN
H3CO
SeCN
, 88%
SeCN
N
H2N
OCH3
, 63%
4k
4l
2ab
, 46%
N
X = S, 12 h
Cl
H3C
N
N
N
R2
N
N
SCN
SCN
SCN
, R2 = H, 88%
2
5c
5d
, 60%
, 59%
5a
5b
, R
=
tBu, 81%
OCH3
Cl
N
N
N
N
N
N
S
On the basis of above discussion and relevant
literatures,10b,14,22,23 a plausible reaction mechanism was
proposed (Scheme 4). Initially, I2 reacts with KXCN in the
SCN
SCN
SCN
5e
5f
5g
, 46%
, 92%
, 53%
aReaction conditions: 1 (0.2 mmol), KXCN (0.3 mmol), I2 (20 mol %),
PIDA (1.5 equiv), H2O (1 mL), room temperature, under air.
presence
of
PIDA
to
generate
electrophilic
iodochalcogenocyanate IXCN.23a Subsequently, Friedel–
Crafts reaction of 1a with IXCN affords intermediate A,
followed by dehydrogenation to give chalcogenocyanated
To highlight the synthetic potential for current
methodology, a gram-scale production was performed,
4
ACS Paragon Plus Environment

Page 5 of 13
The Journal of Organic Chemistry
product 4a and HI.22 However, the direct reaction of
CONCLUSION
1
2
3
4
5
6
7
8
iodide product and KSeCN could not be ruled out to give
selenocyanated product 4a. Next, homolytical cleavage of
4a provides nitrile and selenium radical, which attacks 1a
In conclusion, a novel and practival methodology of
constructing C-S and C-Se bonds at C3-postion of
imidazopyridines via C-H functionalization has been
successfully realized in water. With this green and
sustainable strategy, various chalcogenated and
chalcogenocyanated imidazopyridines were prepared in
good yields by employing catalytic iodine and readily
available KSCN/KSeCN. Moreover, this protocol is
suitable for gram-scale production. Preliminary
mechanistic investigation revealed a radical process might
be involved in this reaction. Compared with previous
reported methods, this is a representative example of
to
form
intermediate
C.10b
Oxidation
and
dehydrogenation of C will yield the selenium-bridged
product 2a and HI, which is oxidized by PIDA to
regenerate I2 to fulfill the catalytic cycle.
Scheme 3. Control experiments
9
I2 (20 mol %)
PIDA (1.5 equiv)
H2O (1 mL), 110 oC,
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(1)
(2)
1a
1a
+
2a
+
4a
+
Ph
KSeCN
N
10 min
I
6
, trace
62%
34%
I2 (20 mol %)
PIDA (1.5 equiv)
6
H2O (1 mL)
110 oC for 3 h
r.t. for 30 min
temperature-controlled
chalcogenation
and
46%
47%
chalcogenocyanation of imidazopyridines in water.
Further application of this methodology is underway in
our laboratory.
I2 (20 mol %)
PIDA (1.5 equiv)
I2 (20 mol %)
PIDA (1.5 equiv)
H2O (1 mL), 110 oC, 3 h
2a
1a
6
+
4a
KSeCN
+
(3)
H2O (1 mL), r.t, 30 min
78%
NR
45%
NR
22%
EXPERIMENTAL SECTION
w/o I2 and PIDA
w/ TEMPO (1 equiv) 69%
w/ TEMPO (1 equiv)
5%
General Information Unless otherwise mentioned, all
materials were commercially obtained and used without
further purification. All procedures were performed under
air. Imidazo[1,2-a]pyridines12a,24 was synthesized according
I2 (20 mol %)
PIDA (1.5 equiv)
H2O (1 mL), 110 oC, 3 h
(4)
(5)
1a
+
KSeCN
2a
, 99%
w/ TEMPO (1 equiv)
w/ BHT (3 equiv)
w/ BQ (2 equiv)
8%
0%
0%
to previously described methods. H NMR, 13C NMR, and
1
N
19F NMR spectra were recorded at 400 MHz or 600 MHz,
101 MHz or 151 MHz, and 565 MHz respectively on a
Bruker DPX instrument using Me4Si as an internal
standard. Chemical shift multiplicities are represented as
follows: (s = singlet, d = doublet, t = triple, m = multiplet,
dd = double doublet, td = triple doublet). Melting points
were measured on a WC-1 instrument and uncorrected.
New compounds for HRMS were tested on a Waters Q-
Tof Micro MS/MS System ESI spectrometer. The structure
of product 2a (CCDC file number 1992870) was further
I2 (20 mol %)
N
PIDA (1.5 equiv)
H2O (1 mL), 110 oC, 3 h
Se
2a
2z
+
+
1a
1z
+
+
KSeCN
N
COOEt
, trace
N
7
81%
34%
I2 (20 mol %)
PIDA (1.5 equiv)
H2O (1 mL), 110 oC, 3 h
4a
1a
1z
+
7
, 20%
N
I2 (20 mol %)
PIDA (1.5 equiv)
H2O (1 mL), 110 oC, 3 h
N
N
(6)
+
KOCN
O
N
8
, 19%
confirmed by X-ray diffraction collected on
a
diffractometer with graphite-monochromated Cu Kα
radiation. ICP-MS analysis was conducted on Agilent
7700S.
Procedure for bis(2-phenylimidazo[1,2-a]pyridin-3-
yl)selane (2a) synthesis. To a 35 mL sealed tube was
added 2-phenylimidazo[1,2-a]pyridine 1 (0.2 mmol),
KSeCN (28.82 mg, 0.2 mmol), I2 (10.15 mg, 20 mol %), and
PIDA (96.6 mg, 1.5 equiv) in H2O (1 mL) under air. The
Scheme 4. The possible reaction mechanism
N
Ph
KXCN + PIDA
N
PIDA
I2
X
6
N
I2
PIDA
Ph
HI
N
HOAc + PhI
IXCN
o
KOAc + PhI
2a
reaction was stirred in a preheated oil bath at 110 C for 3
I2
1a
h, and then cooled down to room temperature. Ethyl
acetate (20 mL) was added and the mixture was extracted
with water (2 × 10 mL). The organic layer was dried over
anhydrous sodium sulfate and concentrated. The residue
was purified by preparative TLC on silica gel plates to give
the corresponding product 2a.
Procedure for bis(2-phenylimidazo[1,2-a]pyridin-3-
yl)sulfan (3a) synthesis. To a 35 mL sealed tube was
added 2-phenylimidazo[1,2-a]pyridine 1 (0.2 mmol), KSCN
(19.44 mg, 0.2 mmol), I2 (10.15 mg, 20 mol %), and PIDA
(96.6 mg, 1.5 equiv) in H2O (1 mL) under air. The reaction
N
N
N
H
Ph
N
Ph
XCN
N
X
N
I
A
Ph
HI
C
1a
N
CN
N
Ph
Ph
N
N
110 o
C
XCN
4a
X
B
o
was stirred in a preheated oil bath at 110 C for 12 h, and
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 13
then cooled down to room temperature. Ethyl acetate (20
HRMS (ESI) m/z: [M + H]+ Calcd for C28H23N4O2Se+:
527.0981, Found: 527.0988.
1
2
3
4
5
6
7
8
mL) was added and the mixture was extracted with water
(2 × 10 mL). The organic layer was dried over anhydrous
sodium sulfate and concentrated. The residue was
purified by preparative TLC on silica gel plates to give the
corresponding product 3a.
Bis(2-(4-(tert-butyl)phenyl)imidazo[1,2-a]pyridin-3-
yl)selane (2c). Yellow solid (55.45 mg, 96% yield); mp 255
– 256 oC. 1H NMR (400 MHz, CDCl3) δ 7.97 – 7.90 (m, 4H),
7.62 – 7.56 (m, 4H), 7.53 (t, J = 6.8 Hz, 2H), 7.46 (d, J = 9.0
Hz, 2H), 7.07-7.03 (m, 2H), 6.26 (td, J = 6.8, 1.1 Hz, 2H),
Procedure for 2-phenyl-3-selenocyanatoimidazo[1,2-
a]pyridine (4a) synthesis. To a 35 mL sealed tube was
13
1.49 – 1.39 (s, 18H). C{1H} NMR (101 MHz, CDCl3) δ 151.9,
added 2-phenylimidazo[1,2-a]pyridine
1
(0.2 mmol),
151.4, 147.2, 131.2, 129.4, 126.2, 126.1, 125.3, 117.1, 112.2, 103.9,
34.9, 31.5. 77Se NMR (76 MHz, CDCl3) δ 19.8. HRMS (ESI)
m/z: [M + H]+ Calcd for C34H35N4Se+: 579.2022, Found:
579.2029.
KSeCN (43.22 mg, 0.3 mmol), I2 (10.15 mg, 20 mol %), and
PIDA (96.6 mg, 1.5 equiv) in H2O (1 mL) under air. The
reaction was stirred at room temperature for 30 min.
Ethyl acetate (20 mL) was added and the mixture was
extracted with water (2 × 10 mL). The organic layer was
dried over anhydrous sodium sulfate and concentrated.
The residue was purified by preparative TLC on silica gel
plates to give the corresponding product 4a.
Procedure for 2-phenyl-3-thiocyanatoimidazo[1,2-
a]pyridine (5a) synthesis. To a 35 mL sealed tube was
added 2-phenylimidazo[1,2-a]pyridine 1a (0.2 mmol),
KSCN (29.15 mg, 0.3 mmol), I2 (10.15 mg, 20 mol %), and
PIDA (96.6 mg, 1.5 equiv) in H2O (1 mL) under air. The
reaction was stirred at room temperature for 12 h. Ethyl
acetate (20 mL) was added and the mixture was extracted
with water (2 × 10 mL). The organic layer was dried over
anhydrous sodium sulfate and concentrated. The residue
was purified by preparative TLC on silica gel plates to give
the corresponding product 5a.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Bis(2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)selane
(2d). Light yellow solid (28.85 mg, 54% yield); mp 291 –
o
1
292 C. H NMR (400 MHz, CDCl3) δ 8.01 – 7.91 (m, 4H),
7.62 (dd, J = 6.9, 1.0 Hz, 2H), 7.59 – 7.51 (m, 4H), 7.49 (d, J
= 9.0 Hz, 2H), 7.15-7.11 (m, 2H), 6.45 (td, J = 6.9, 1.1 Hz,
2H). 13C{1H} NMR (101 MHz, CDCl3) δ 150.3, 147.3, 134.9,
132.5, 130.8, 128.7, 126.6, 125.8, 117.5, 112.9, 103.5. 77Se NMR
(76 MHz, CDCl3) δ 23.7. HRMS (ESI) m/z: [M + H]+ Calcd
for C26H17Cl2N4Se+: 534.9990, Found: 534.9991.
Bis(2-(m-tolyl)imidazo[1,2-a]pyridin-3-yl)selane
(2e).
o
1
Yellow solid (22.10 mg, 45% yield); mp 185 – 186 C. H
NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.6 Hz, 2H), 7.79 (s,
2H), 7.64 – 7.52 (m, 2H), 7.53 – 7.43 (m, 4H), 7.35 (d, J =
7.6 Hz, 2H), 7.11-7.07 (m, 2H), 6.35 (td, J = 6.8, 1.1 Hz, 2H),
2.51 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 151.6, 147.2,
138.1, 133.9, 130.3, 129.5, 128.3, 126.8, 126.23, 126.21, 117.2,
112.4, 103.7, 21.6. 77Se NMR (76 MHz, CDCl3) δ 23.9. HRMS
(ESI) m/z: [M + H]+ Calcd for C28H23N4Se+: 495.1083,
Found: 495.1089.
Procedure for the Gram-Scale Production of 2a To a
100 mL sealed tube was added 2-phenylimidazo[1,2-
a]pyridine 1 (0.97g, 5 mmol), KSeCN (0.72g, 5 mmol), I2
(253.81 mg, 20 mol %), and PIDA (2.42g, 1.5 equiv) in H2O
(25 mL) under air. The reaction was stirred in a preheated
Bis(2-(3-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)selane (2f).
Light yellow solid (52.36 mg, 98% yield); mp 254 – 256 oC.
1H NMR (400 MHz, CDCl3) δ 8.00 (t, J = 4.9 Hz, 2H), 7.95
– 7.86 (m, 2H), 7.62 (d, J = 6.9 Hz, 2H), 7.55 – 7.45 (m, 6H),
7.17-7.13 (m, 2H), 6.46 (td, J = 6.9, 1.1 Hz, 2H). 13C{1H} NMR
(101 MHz, CDCl3) δ 150.1, 147.3, 135.9, 134.5, 129.7, 129.6,
128.8, 127.7, 126.7, 125.9, 117.5, 112.9, 103.8. HRMS (ESI) m/z:
[M + H]+ Calcd for C26H17Cl2N4Se+: 534.9990, Found:
534.9996.
o
oil bath at 110 C for 3 h, and then cooled down to room
temperature. Ethyl acetate (50 mL) was added and the
mixture was extracted with water (2 × 50 mL). The
organic layer was dried over anhydrous sodium sulfate
and concentrated. The residue was purified by silica gel
column chromatography (EA/PE = 1:3) to afford 2a in 80%
yield (0.93 g).
Bis(2-phenylimidazo[1,2-a]pyridin-3-yl)selane (2a). Light
Bis(2-(2-methoxyphenyl)imidazo[1,2-a]pyridin-3-yl)selane
(2g). Light yellow solid (32.06 mg, 61% yield); mp 214 – 216
o
1
yellow solid (46.07 mg, 99% yield); mp 244 - 245 C. H
NMR (400 MHz, CDCl3) δ 8.02 – 7.98 (m, 4H), 7.60-7.56
(m, 4H), 7.55 – 7.50 (m, 4H), 7.47 (d, J = 9.0 Hz, 2H), 7.09-
7.04 (m, 2H), 6.31 (td, J = 6.8, 1.1 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 151.5, 147.2, 134.1, 129.7, 128.7, 128.4, 126.2,
126.0, 117.2, 112.5, 103.7. 77Se NMR (76 MHz, CDCl3) δ 20.8.
HRMS (ESI) m/z: [M + K]+ Calcd for C26H18N4SeK+:
505.0329, Found: 505.0335.
1
oC. H NMR (400 MHz, CDCl3) δ 7.57 – 7.47 (m, 8H), 7.17
(td, J = 7.5, 0.9 Hz, 2H), 7.14 – 7.06 (m, 4H), 6.46 (td, J =
6.8, 1.1 Hz, 2H), 3.88 – 3.80 (m, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 157.3, 148.8, 147.2, 132.4, 130.3, 125.6, 125.4,
123.5, 120.7, 117.3, 112.3, 111.2, 105.7, 55.5. 77Se NMR (76 MHz,
CDCl3) δ 44.8. HRMS (ESI) m/z: [M + H]+ Calcd for
C28H23N4O2Se+: 527.0981, Found: 527.0985.
Bis(2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-3-yl)selane
(2b). Yellow solid (23.65 mg, 45% yield); mp 198 – 200 oC.
1H NMR (400 MHz, CDCl3) δ 8.02 – 7.92 (m, 4H), 7.62 (t, J
= 7.8 Hz, 2H), 7.49 – 7.42 (m, 2H), 7.14 – 7.04 (m, 6H),
6.43 – 6.32 (m, 2H), 3.95 (s, 6H). 13C{1H} NMR (101 MHz,
CDCl3) δ 160.2, 151.2, 147.1, 130.9, 126.5, 126.2, 126.1, 117.0,
113.9, 112.5, 102.9, 55.4. 77Se NMR (76 MHz, CDCl3) δ 23.8.
Bis(2-(2-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)selane
(2h). Light yellow solid (48.64 mg, 97% yield); mp 216 –
o
1
221 C. H NMR (400 MHz, CDCl3) δ 7.64 (td, J = 7.4, 1.7
Hz, 2H), 7.58 – 7.48 (m, 6H), 7.41 – 7.29 (m, 4H), 7.16 –
7.09 (m, 2H), 6.47 (td, J = 6.8, 1.2 Hz, 2H). 13C{1H} NMR
(101 MHz, CDCl3) δ 160.1 (JC-F = 250.1 Hz), 147.4, 146.8, 132.6,
(JC-F = 2.6 Hz), 130.8 (JC-F = 8.1 Hz), 126.1, 125.4, 124.3, (JC-F
=
3.6 Hz), 122.4 (JC-F = 14.1 Hz), 117.5, 116.2 (JC-F = 22.0 Hz),
6
ACS Paragon Plus Environment

Page 7 of 13
The Journal of Organic Chemistry
Bis(7-bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)selane (2o).
112.7, 105.6. 19F NMR (376 MHz, CDCl3) δ -113.08. 77Se NMR
o
1
(76 MHz, CDCl3) δ 33.5. HRMS (ESI) m/z: [M + H]+ Calcd
Yellow solid (54.22 mg, 87% yield); mp 242 – 243 C. H
NMR (400 MHz, CDCl3) δ 8.00 – 7.92 (m, 4H), 7.65 (dd, J
= 1.9, 0.6 Hz, 2H), 7.63 – 7.48 (m, 6H), 7.30 (dd, J = 7.3, 0.6
Hz, 2H), 6.40 (dd, J = 7.3, 1.9 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 152.2, 147.3, 133.5, 129.6, 129.1, 128.6, 126.2,
120.5, 119.6, 116.4, 103.9. 77Se NMR (76 MHz, CDCl3) δ 22.9.
HRMS (ESI) m/z: [M + H]+ Calcd for C26H17Br2N4Se+:
622.8980, Found: 622.8989.
1
2
3
4
C26H17F2N4Se+: 503.0581, Found: 503.0583.
Bis(2-(2-bromophenyl)imidazo[1,2-a]pyridin-3-yl)selane
(2i). Light yellow solid (19.34 mg, 32% yield); mp 215 – 217
oC. H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.9 Hz, 2H),
1
5
6
7
7.59 – 7.52 (m, 4H), 7.47 (t, J = 3.6 Hz, 4H), 7.44 – 7.36 (m,
2H), 7.23 – 7.15 (m, 2H), 6.61 – 6.54 (m, 2H). C{1H} NMR
13
(101 MHz, CDCl3) δ 151.2, 146.9, 135.6, 133.2, 132.9, 130.3,
127.2, 126.1, 125.6, 124.6, 117.6, 113.0, 105.5. 77Se NMR (76
MHz, CDCl3) δ 35.2. HRMS (ESI) m/z: [M + H]+ Calcd for
C26H17Br2N4Se+: 622.8980, Found: 622.8985.
Bis(6-methoxy-2-phenylimidazo[1,2-a]pyridin-3-yl)selane
(2j). Light yellow solid (45.72 mg, 87% yield); mp 262 –
8
9
Bis(8-methoxy-2-phenylimidazo[1,2-a]pyridin-3-yl)selane
(2p). Yellow solid (30.80 mg, 59% yield); mp 248 – 254 oC.
1H NMR (400 MHz, CDCl3) δ 7.98 (dd, J = 5.2, 3.2 Hz, 4H),
7.60 – 7.54 (m, 4H), 7.54 – 7.48 (m, 2H), 7.31 (d, J = 7.5 Hz,
2H), 6.75 (d, J = 2.4 Hz, 2H), 6.02 (dd, J = 7.5, 2.5 Hz, 2H),
3.80 – 3.70 (m, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 159.1,
151.2, 148.6, 134.2, 129.5, 128.6, 128.4, 126.4, 107.2, 102.6, 94.7,
55.5. 77Se NMR (76 MHz, CDCl3) δ 21.1. HRMS (ESI) m/z:
[M + H]+ Calcd for C28H23N4O2Se+: 527.0981, Found:
527.0987.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
1
263 C. H NMR (400 MHz, CDCl3) δ 8.40 (dd, J = 8.2, 1.1
Hz, 4H), 7.65 – 7.48 (m, 4H), 7.50 – 7.34 (m, 6H), 6.87 (dd,
J = 9.6, 2.4 Hz, 2H), 2.92 – 2.83 (s, 6H). C{1H} NMR (101
13
MHz, CDCl3) δ 149.8, 149.7, 144.2, 134.2, 129.0, 128.8, 128.6,
122.0, 117.5, 107.4, 102.2, 55.0. HRMS (ESI) m/z: [M + H]+
Calcd for C28H23N4O2Se+: 527.0981, Found: 527.1003.
Bis(8-methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)selane
(2q). Yellow solid (38.49 mg, 78% yield); mp 219 – 220 oC.
1H NMR (400 MHz, CDCl3) δ 8.02 – 7.93 (m, 4H), 7.65 –
7.44 (m, 6H), 7.38 (dd, J = 19.5, 6.8 Hz, 2H), 6.92 – 6.76 (m,
2H), 6.24 (t, J = 6.9 Hz, 2H), 2.56 – 2.42 (s, 6H). 13C{1H}
NMR (101 MHz, CDCl3) δ 151.1, 147.5, 134.4, 129.9, 128.5,
128.4, 127.2, 124.9, 124.0, 112.4, 104.3, 16.7. 77Se NMR (76
MHz, CDCl3) δ 27.1. HRMS (ESI) m/z: [M + H]+ Calcd for
C28H23N4Se+: 495.1083, Found: 495.1088.
Bis(8-chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)selane (2r).
Light yellow solid (45.95 mg, 86% yield); mp 237 – 238 oC.
1H NMR (400 MHz, CDCl3) δ 8.03 – 7.94 (m, 4H), 7.64 –
7.49 (m, 6H), 7.42 (dt, J = 9.9, 4.9 Hz, 2H), 7.16 (dt, J = 7.4,
3.6 Hz, 2H), 6.26 (t, J = 7.1 Hz, 2H). 13C{1H} NMR (101 MHz,
CDCl3) δ 152.1, 144.6, 133.5, 129.9, 129.0, 128.4, 125.2, 124.8,
123.0, 112.1, 105.4. 77Se NMR (76 MHz, CDCl3) δ 40.3. HRMS
(ESI) m/z: [M + H]+ Calcd for C26H17Cl2N4Se+: 534.9990,
Found: 534.9998.
Bis(6-chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)selane (2k).
Light yellow solid (41.14 mg, 77% yield); mp 288 – 289 C.
o
1H NMR (400 MHz, CDCl3) δ 8.03 – 7.96 (m, 4H), 7.66 –
7.60 (m, 4H), 7.60 – 7.53 (m, 4H), 7.44 (dd, J = 9.4, 0.7 Hz,
2H), 7.07 (dd, J = 9.4, 2.0 Hz, 2H). 13C{1H} NMR (101 MHz,
CDCl3) δ 152.5, 145.7, 133.2, 129.4, 129.3, 128.9, 127.9, 124.3,
121.2, 117.6, 103.9. 77Se NMR (76 MHz, CDCl3) δ 24.8.
HRMS (ESI) m/z: [M + H]+ Calcd for C26H17Cl2N4Se+:
534.9990, Found: 534.9993.
Bis(6-bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)selane (2l).
Light yellow solid (57.96 mg, 93% yield); mp 295 – 296 oC.
1H NMR (400 MHz, CDCl3) δ 8.07 – 7.98 (m, 4H), 7.74 (dd,
J = 1.8, 0.7 Hz, 2H), 7.67 – 7.59 (m, 4H), 7.57-7.54 (m, 2H),
7.39 (dd, J = 9.4, 0.6 Hz, 2H), 7.17 (dd, J = 9.4, 1.9 Hz, 2H).
13C{1H} NMR (101 MHz, CDCl3) δ 152.2, 145.8, 133.1, 130.1,
129.4, 129.4, 129.0, 126.5, 117.9, 107.7, 103.5. HRMS (ESI)
m/z: [M + H]+ Calcd for C26H17Br2N4Se+: 622.8980, Found:
622.8998.
Dimethyl 3,3'-selenobis(2-phenylimidazo[1,2-a]pyridine-8-
carboxylate (2s). Light yellow solid (41.87 mg, 72% yield);
Bis(7-methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)selane
(2m). Light yellow solid (34.54 mg, 70% yield); mp 188 –
o
1
mp 248 – 249 C. H NMR (400 MHz, CDCl3) δ 8.10 – 8.01
(m, 4H), 7.84 (dt, J = 13.9, 6.9 Hz, 2H), 7.74 (dd, J = 6.8, 1.2
Hz, 2H), 7.66 – 7.49 (m, 6H), 6.45 – 6.34 (m, 2H), 4.02 –
o
1
189 C. H NMR (400 MHz, CDCl3) δ 8.07 – 7.94 (m, 4H),
7.61 – 7.55 (m, 4H), 7.55 – 7.48 (m, 2H), 7.39 (d, J = 7.1 Hz,
2H), 7.24 – 7.20 (m, 2H), 6.16 (dd, J = 7.0, 1.6 Hz, 2H), 2.25
13
3.91 (m, 6H). C{1H} NMR (101 MHz, CDCl3) δ 152.2, 147.3,
(t, J = 7.3 Hz, 6H). C{1H} NMR (101 MHz, CDCl3) δ 151.2,
133.5, 129.6, 129.1, 128.6, 126.2, 120.5, 119.6, 103.9. 77Se NMR
(76 MHz, CDCl3) δ 30.0. HRMS (ESI) m/z: [M + H]+ Calcd
for C30H23N4O4Se+: 583.0879, Found: 583.0888.
13
147.6, 137.5, 134.2, 129.6, 128.6, 128.4, 125.2, 115.7, 115.1, 102.9,
21.2. 77Se NMR (76 MHz, CDCl3) δ 22.5. HRMS (ESI) m/z:
[M + H]+ Calcd for C28H23N4Se+: 495.1083, Found: 495.1089.
Bis(7-chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)selane (2n).
Bis(6-phenylimidazo[2,1-b]thiazol-5-yl)selane (2t). Yellow
solid (36.29 mg, 76% yield); mp 201 – 202 oC. 1H NMR (400
MHz, CDCl3) δ 7.97 (dd, J = 5.2, 3.3 Hz, 4H), 7.55 – 7.47 (m,
4H), 7.47 – 7.38 (m, 2H), 6.59 (d, J = 4.5 Hz, 2H), 6.49 (d, J
= 4.5 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 152.1, 151.5,
133.9, 128.7, 128.5, 128.3, 118.8, 112.3, 103.9. 77Se NMR (76
MHz, CDCl3) δ 79.9. HRMS (ESI) m/z: [M + H]+ Calcd for
C22H15N4S2Se+: 478.9898, Found: 478.9907.
o
Light yellow solid (39.01 mg, 73% yield); mp 251 – 252 C.
1H NMR (400 MHz, CDCl3) δ 8.01 – 7.92 (m, 4H), 7.66 –
7.52 (m, 6H), 7.50 – 7.45 (m, 2H), 7.37 (dt, J = 11.6, 5.8 Hz,
13
2H), 6.29 (dd, J = 7.3, 2.1 Hz, 2H). C{1H} NMR (101 MHz,
CDCl3) δ 152.4, 147.0, 133.5, 133.1, 129.6, 129.1, 128.6, 126.2,
116.2, 114.1, 104.0. 77Se NMR (76 MHz, CDCl3) δ 22.8. HRMS
(ESI) m/z: [M + H]+ Calcd for C26H17Cl2N4Se+: 534.9990,
Found: 534.9992.
Bis(6-phenyl-2,3-dihydroimidazo[2,1-b]thiazol-5-yl)selane
o
(2u). Yellow solid (41.41 mg, 86% yield); mp 251 – 252 C.
1H NMR (400 MHz, CDCl3) δ 7.89 (dd, J = 5.2, 3.3 Hz, 4H),
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 13
7.43 (dd, J = 10.3, 4.7 Hz, 4H), 7.37 – 7.30 (m, 2H), 3.54 –
δ 7.76 – 7.70 (m, 1H), 7.38 (s, 1H), 7.37 – 7.27 (m, 3H), 3.81
13
3.34 (m, 8H). C{1H} NMR (101 MHz, CDCl3) δ 151.9, 151.1,
(s, 3H).
1
2
3
4
5
6
7
8
134.0, 128.3, 127.9, 127.8, 108.9, 46.0, 34.0. 77Se NMR (76
MHz, CDCl3) δ 101.9. HRMS (ESI) m/z: [M + H]+ Calcd for
C22H19N4S2Se+: 483.0211, Found: 483.0219.
Bis(2-phenylimidazo[1,2-a]pyridin-3-yl)sulfane
(3a)18d
.
Light yellow solid (35.99 mg, 86% yield); mp 251 – 252 oC.
1H NMR (400 MHz, CDCl3) δ 8.15 – 8.05 (m, 4H), 7.65 –
7.58 (m, 4H), 7.58 – 7.52 (m, 4H), 7.52 – 7.46 (m, 2H), 7.11-
7.07 (m, 2H), 6.34 (td, J = 6.9, 1.1 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 150.9, 146.5, 133.8, 129.6, 128.9, 128.6, 126.4,
125.3, 117.4, 112.6, 107.5.
Bis(2-(furan-2-yl)imidazo[1,2-a]pyridin-3-yl)selane
(2v).
o
1
Brown solid (20.04 mg, 45% yield); mp 230 – 235 C. H
NMR (400 MHz, CDCl3) δ 8.23 (d, J = 6.9 Hz, 2H), 7.71 (dd,
J = 1.6, 0.6 Hz, 2H), 7.53 (d, J = 9.0 Hz, 2H), 7.32 (dd, J =
3.4, 0.5 Hz, 2H), 7.21 – 7.07 (m, 2H), 6.68 (dd, J = 3.4, 1.8
Hz, 2H), 6.63 (td, J = 6.9, 1.1 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 148.8, 147.6, 143.2, 142.4, 126.7, 125.8, 117.4,
113.2, 111.8, 110.3, 100.6. 77Se NMR (76 MHz, CDCl3) δ 60.5.
HRMS (ESI) m/z: [M + H]+ Calcd for C22H15N4O2Se+:
447.0355, Found: 447.0362.
Bis(2-(4-(tert-butyl)phenyl)imidazo[1,2-a]pyridin-3-
yl)sulfane (3b)18d. Yellow solid (51.44 mg, 97% yield); mp
267 – 268 oC. 1H NMR (400 MHz, CDCl3) δ 8.06 – 7.96 (m,
4H), 7.64 – 7.58 (m, 4H), 7.57 – 7.50 (m, 2H), 7.48 (t, J =
7.4 Hz, 2H), 7.08-7.04 (m, 2H), 6.26 (td, J = 6.8, 1.1 Hz, 2H),
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
1.52 – 1.38 (s, 18H). C{1H} NMR (101 MHz, CDCl3) δ 152.1,
Bis(2-(thiophen-2-yl)imidazo[1,2-a]pyridin-3-yl)selane
150.9, 146.5, 130.9, 129.3, 126.2, 125.5, 125.4, 117.2, 112.3, 107.7,
34.9, 31.5.
o
(2w). Yellow solid (32.47 mg, 68% yield); mp 212 – 214 C.
1H NMR (600 MHz, CDCl3) δ 8.07 (d, J = 3.5 Hz, 1H), 7.94
(d, J = 6.9 Hz, 1H), 7.53 (d, J = 5.0 Hz, 1H), 7.50 (d, J = 8.9
Hz, 1H), 7.29 – 7.24 (m, 1H), 7.14 – 7.07 (m, 1H), 6.52 (t, J =
Bis(2-(3-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)sulfane
(3c). Light yellow solid (46.66 mg, 96% yield); mp 262 –
266 oC. 1H NMR (400 MHz, CDCl3) δ 8.12 (t, J = 1.7 Hz, 2H),
8.05-8.03 (m, 2H), 7.64 – 7.58 (m, 2H), 7.58 – 7.49 (m, 6H),
7.19-7.14 (m, 2H), 6.48 (td, J = 6.9, 1.1 Hz, 2H). 13C{1H} NMR
(101 MHz, CDCl3) δ 149.5, 146.6, 135.5, 134.7, 129.9, 129.4,
129.0, 127.6, 126.8, 125.1, 117.7, 113.0, 107.4. HRMS (ESI) m/z:
[M + H]+ Calcd for C26H17Cl2N4S+: 487.0546, Found:
487.0549.
Bis(2-(2-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)sulfane
(3d)18d. Light yellow solid (44.95 mg, 97% yield); mp 243 –
244 oC.1H NMR (400 MHz, CDCl3) δ 7.70 (td, J = 7.3, 1.6 Hz,
2H), 7.61 – 7.46 (m, 6H), 7.42 – 7.30 (m, 4H), 7.18 – 7.09
(m, 2H), 6.45 (td, J = 6.8, 0.9 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 160.2 (JC-F = 251.3 Hz), 146.7, 146.2, 132.6,
13
6.8 Hz, 1H). C{1H} NMR (151 MHz, CDCl3) δ 147.5, 145.8,
136.8, 127.8, 127.2, 126.6, 126.2, 125.9, 117.2, 113.1, 101.0. 77Se
NMR (76 MHz, CDCl3) δ 42.5. HRMS (ESI) m/z: [M + H]+
Calcd for C22H15N4S2Se+: 478.9898, Found: 478.9903.
Bis(2-methylimidazo[1,2-a]pyridin-3-yl)selane (2x). Yellow
solid (23.89 mg, 70% yield); mp 195 – 198 oC. 1H NMR (400
MHz, CDCl3) δ 8.33 (d, J = 6.8 Hz, 2H), 7.46 (t, J = 17.2 Hz,
2H), 7.22 – 7.13 (m, 2H), 6.89 – 6.77 (m, 2H), 2.71 (s, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 149.8, 147.1, 125.6, 125.1,
117.0, 112.6, 103.8, 15.1. 77Se NMR (76 MHz, CDCl3) δ 16.4.
HRMS (ESI) m/z: [M + H]+ Calcd for C16H15N4Se+: 343.0457,
Found: 343.0466.
Bis(imidazo[1,2-a]pyridin-3-yl)selane (2y). Light yellow
solid (26.31 mg, 84% yield); mp 275 – 280 oC. 1H NMR (400
MHz, CDCl3) δ 8.52 (d, J = 6.9 Hz, 2H), 7.97 (s, 2H), 7.60
(d, J = 9.0 Hz, 2H), 7.29 – 7.19 (m, 2H), 6.93 (td, J = 6.8, 0.9
Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 147.9, 141.5, 125.8,
124.9, 118.0, 113.3, 104.6. 77Se NMR (76 MHz, CDCl3) δ 35.8.
HRMS (ESI) m/z: [M + H]+ Calcd for C14H11N4Se+: 315.0144,
Found: 315.0146.
Diethyl 3,3'-selenobis(imidazo[1,2-a]pyridine-2-carboxylate)
(2z). White solid (14.78 mg, 31% yield); mp 158 – 160 oC. 1H
NMR (400 MHz, CDCl3) δ 9.06 (dt, J = 7.0, 1.0 Hz, 2H),
7.72 – 7.57 (m, 2H), 7.33-7.29 (m, 2H), 6.92 (td, J = 6.9, 1.1
Hz, 2H), 4.61 (q, J = 7.1 Hz, 4H), 1.54 (t, J = 7.1 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 163.6, 147.1, 140.1, 127.8,
127.4, 118.8, 114.6, 109.0, 61.8, 14.5. 77Se NMR (76 MHz,
CDCl3) δ 105.8. HRMS (ESI) m/z: [M + H]+ Calcd for
C20H19N4O4Se+: 459.0566, Found: 459.0573.
(JC-F = 2.3 Hz), 131.0 (JC-F = 8.2 Hz), 126.3, 124.6, 124.3, (JC-F =
3.6 Hz), 122.0 (JC-F = 14.1 Hz), 117.7, 116.3 (JC-F = 22.1 Hz),
112.8, 109.6. 19F NMR (376 MHz, CDCl3) δ -113.00.
Bis(6-fluoro-2-phenylimidazo[1,2-a]pyridin-3-yl)sulfane
(3e). Light yellow solid (34.97 mg, 77% yield); mp 292 –
o
1
293 C. H NMR (400 MHz, CDCl3) δ 8.06 – 7.98 (m, 4H),
7.68 – 7.54 (m, 6H), 7.49-7.45 (m, 2H), 7.40 – 7.34 (m, 2H),
7.05-7.00 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 153.4
(JC-F = 206.0 Hz), 152.2 (JC-F = 31.9 Hz), 144.1, 133.2, 129.4 (JC-
F = 4.6 Hz), 128.8, 118.4 (JC-F = 25.4 Hz), 117.8 (JC-F = 8.6 Hz),
112.7, 112.3, 108.9. 19F NMR (376 MHz, CDCl3) δ -137.73.
HRMS (ESI) m/z: [M + H]+ Calcd for C26H17F2N4S+: 455.1137,
Found: 455.1146.
Bis(6-methoxy-2-phenylimidazo[1,2-a]pyridin-3-yl)sulfane
(3f). Light yellow solid (37.78 mg, 79% yield); mp 264 –
o
1
266 C. H NMR (400 MHz, CDCl3) δ 8.55 – 8.47 (m, 4H),
7.59 (dd, J = 10.6, 4.8 Hz, 4H), 7.49 – 7.41 (m, 6H), 6.90
(dd, J = 9.5, 2.4 Hz, 2H), 2.88 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 149.9, 149.1, 143.5, 134.0, 128.89, 128.86,
128.8, 122.1, 117.6, 106.6, 106.0, 54.9. HRMS (ESI) m/z: [M +
H]+ Calcd for C28H23N4O2S+: 479.1536, Found: 479.1540.
Bis(7-bromo-2-phenylimidazo[1,2-a]pyridin-3-yl)sulfane
(3g). Light yellow solid (44.47 mg, 77% yield); mp 270 –
1,3,5-Trimethoxy-2-selenocyanatobenzene (2ab)15. Brown
solid (28.70 mg, 53% yield); mp 148 – 150 oC. 1H NMR (400
MHz, CDCl3) δ 6.17 (s, 2H), 3.91 (s, 6H), 3.84 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 164.2, 160.8, 101.9, 91.4,
89.8, 56.4, 55.6.
1-Methyl-3-selenocyanato-1H-indole (2ac)25. Yellow solid
(19.3 mg, 41%); mp 106-107 °C. 1H NMR (400 MHz, CDCl3)
o
1
272 C. H NMR (400 MHz, CDCl3) δ 8.10 – 8.01 (m, 4H),
7.72 – 7.53 (m, 8H), 7.32 (d, J = 7.2 Hz, 2H), 6.42 (dd, J =
8
ACS Paragon Plus Environment

Page 9 of 13
The Journal of Organic Chemistry
7.3, 1.9 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 151.6,
146.7, 133.2, 129.5, 129.3, 128.8, 125.5, 120.7, 119.8, 116.6, 107.7.
HRMS (ESI) m/z: [M + H]+ Calcd for C26H17Br2N4S+:
574.9535, Found: 574.9542.
CDCl3) δ 148.6, 147.5, 144.6, 143.9, 128.0, 125.2, 118.0, 114.4,
111.8, 111.2, 98.5, 91.8.
1
2
3
4
5
6
7
8
6-Methyl-2-phenyl-3-selenocyanatoimidazo[1,2-a]pyridine
(4f)15. Yellow solid (60.6 mg, 97% yield); mp 142-145 oC. 1H
NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.94 (dt, J = 8.5, 1.5
Hz, 2H), 7.60 (d, J = 9.1, 1H), 7.50 – 7.47 (m, 2H), 7.45 -
7.40 (m, 1H), δ 7.26 (s, 1H), δ 2.43 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 153.1, 147.4, 132.6, 130.8, 129.1, 129.0, 128.6,
124.3, 123.3, 117.3, 99.3, 93.1, 18.5.
Bis(8-chloro-2-phenylimidazo[1,2-a]pyridin-3-yl)sulfane
(3h). Light yellow solid (42.29 mg, 87% yield); mp 286 –
o
1
290 C. H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 6.9 Hz,
4H), 7.67 – 7.51 (m, 6H), 7.42 (t, J = 11.4 Hz, 2H), 7.17 (d, J =
7.3 Hz, 2H), 6.28 (t, J = 7.1 Hz, 2H). 13C{1H} NMR (101 MHz,
CDCl3) δ 151.6, 143.9, 133.2, 129.8, 129.3, 128.7, 125.4, 124.0,
123.2, 112.3, 109.2. HRMS (ESI) m/z: [M + H]+ Calcd for
C26H17Cl2N4S+: 487.0546, Found: 487.0552.
6-Bromo-2-phenyl-3-selenocyanatoimidazo[1,2-a]pyridine
(4g)15. Yellow solid (36.9 mg, 49% yield); mp 167-168 oC. 1H
NMR (400 MHz, CDCl3) δ 8.57 (dd, J = 1.8, 0.8 Hz, 1H),
8.00 – 7.92 (m, 2H), 7.64 (dd, J = 9.4, 0.6 Hz, 1H), 7.57 –
7.43 (m, 4H). 13C{1H} NMR (101 MHz, CDCl3) δ 154.1, 147.0,
132.0, 131.4, 129.5, 129.1, 128.7, 125.7, 118.7, 109.2, 98.5, 94.1.
8-Methoxy-2-phenyl-3-selenocyanatoimidazo[1,2-a]pyridine
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Bis(6-phenyl-2,3-dihydroimidazo[2,1-b]thiazol-5-yl)sulfane
(3i). Light yellow solid (36.46 mg, 84% yield); mp 288 –
o
1
290 C. H NMR (400 MHz, CDCl3) δ 7.99 – 7.93 (m, 4H),
7.45 (dd, J = 10.4, 4.7 Hz, 4H), 7.38 – 7.31 (m, 2H), 3.54 –
3.40 (m, 8H). 13C{1H} NMR (101 MHz, CDCl3) δ 151.8, 150.3,
133.6, 128.4, 127.9, 127.7, 114.2, 45.3, 34.3. HRMS (ESI) m/z:
[M + H]+ Calcd for C22H19N4S3+: 435.0767, Found: 435.0770.
o
(4h). Yellow solid (62.1 mg, 95% yield); mp 121-122 C. 1H
NMR (400 MHz, CDCl3) δ 8.20 (d, J = 7.5 Hz, 1H), 7.96 –
7.93 (m, 2H), 7.51 – 7.47 (m, 2H), 7.45 – 7.40 (m, 1H), 6.96
(d, J = 2.4, 1H), 7.65 (dd, J = 7.4, 4.6 Hz, 1H), 3.89 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 160.1, 153.6, 150.0, 132.6,
129.1, 128.9, 128.6, 125.7, 108.9, 99.4, 95.5, 91.8, 55.9. 77Se
NMR (76 MHz, CDCl3) δ 177.7. HRMS (ESI) m/z: [M + H]+
Calcd for: C15H12N3OSe+: 330.0140, Found: 330.0141.
2-Phenyl-3-selenocyanatoimidazo[1,2-a]pyridine
(4a)15.
Yellow solid (55.1 mg, 92% yield); mp 166-168 C.1H NMR
(400 MHz, CDCl3) δ 8.45 (d, J = 6.8 Hz, 1H), 8.01 – 7.94 (m,
2H), 7.76 (d, J = 9.0 Hz, 1H), 7.55 – 7.49 (m, 2H), 7.49 –
7.39 (m, 2H), 7.11 (td, J = 6.8, 1.0 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 153.6, 148.5, 132.5, 129.3, 129.2, 128.6, 127.8,
125.5, 118.2, 114.3, 98.8, 93.5.
o
7-Methyl-2-phenyl-3-selenocyanatoimidazo[1,2-a]pyridine
o
(4i). Yellow solid (50.4 mg, 81% yield); mp 153-154 C.1H
2-(4-Chlorophenyl)-3-selenocyanatoimidazo[1,2-a]pyridine
NMR (400 MHz, CDCl3) δ 8.29 (d, J = 7.0 Hz, 1H), 7.98 –
7.92 (m, 2H), 7.54 – 7.40 (m, 4H), 6.91 (dd, J = 7.0, 1.6 Hz,
1H), 2.48 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 153.5,
148.8, 139.3, 132.6, 129.1, 129.0, 128.6, 127.6, 116.8, 116.6, 99.1,
92.6, 21.4. 77Se NMR (76 MHz, CDCl3) δ 175.7. HRMS (ESI)
m/z: [M + H]+ Calcd for: C15H12N3Se+: 314.0191, Found:
314.0192.
o
(4b)15. Yellow solid (38.9 mg, 58% yield); mp 155-157 C.1H
NMR (400 MHz, CDCl3) δ 8.45 (dd, J = 5.8, 1.0 Hz, 1H),
7.98 – 7.90 (m, 2H), 7.75 (d, J = 9.0 Hz, 1H), 7.53 – 7.46 (m,
3H), 7.13 (td, J = 6.9, 1.1 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 152.4, 148.5, 135.5, 130.9, 130.3, 128.9, 128.0, 125.5,
118.2, 114.5, 98.5, 93.5.
3-Selenocyanato-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-
6-Phenyl-5-selenocyanato-2,3-dihydroimidazo[2,1-
b]thiazole (4j). Yellow solid (52.06 mg, 85% yield); mp
a]pyridine (4c)15. Yellow solid (57.2 mg, 79% yield); mp
o
o
1
223-225 C.1H NMR (400 MHz, CDCl3) δ 8.45 (dt, J = 8.0,
192-193 C. H NMR (400 MHz, CDCl3) δ 7.84 – 7.77 (m,
2H), 7.49 – 7.41 (m, 2H), 7.38 (dt, J = 9.6, 4.3 Hz, 1H), 4.37
(t, J = 7.4 Hz, 2H), 3.92 (t, J = 7.4 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 154.7, 154.6, 132.5, 128.6, 128.5, 127.8, 99.5,
97.5, 46.7, 33.8. HRMS (ESI) m/z: [M + H]+ Calcd for
C12H10N3SSe +: 307.9755, Found: 307.9754.
1.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 2H),7.77 – 7.75 (m, 3H), 7.50
– 7.46 (m, 1H), 7.14 (td, J = 6.8, 1.0 Hz, 1H). 13C{1H} NMR
(101 MHz, CDCl3) δ 151.8, 148.5, 135.9, 131.1 (JC-F = 32.8 Hz),
129.3, 128.2, 125.6, 125.5, 124.0 (JC-F = 273.3 Hz), 118.3, 114.7,
98.6, 94.3. 19F NMR (376 MHz, CDCl3) δ -62.61.
2-(3-Chlorophenyl)-3-selenocyanatoimidazo[1,2-a]pyridine
N,N-dimethyl-4-selenocyanatoaniline (4k)25. Yellow solid
(4d). Yellow solid (32.5 mg, 48% yield); mp 174-175 C. H
NMR (600 MHz, CDCl3) δ 8.45 (d, J = 6.8 Hz, 1H), 8.00 (s,
1H), 7.89 (dd, J = 7.0, 1.6 Hz, 1H), 7.76 (d, J = 9.0 Hz, 1H),
7.51 – 7.40 (m, 3H), 7.14 (t, J = 6.8 Hz, 1H). 13C{1H} NMR
(151 MHz, CDCl3) δ 152.0, 148.5, 134.7, 134.2, 129.9, 129.3,
129.1, 128.1, 127.2, 125.5, 118.3, 114.6, 98.5, 93.8. 77Se NMR (76
MHz, CDCl3) δ 172.5. HRMS (ESI) m/z: [M + H]+ Calcd for:
C14H9ClN3Se+: 333.9645, Found: 333.9644.
(39.4 mg, 88% yield); mp 101-102 C.1H NMR (400 MHz,
o
1
o
CDCl3) δ 7.53-7.49 (m, 2H), 6.64 (dt, J = 10.2, 3.2 Hz, 2H),
13
2.99 (s, 6H). C{1H} NMR (101 MHz, CDCl3) δ 151.7, 136.4,
113.3, 104.5, 102.8, 40.1.
2-Methyl-4-selenocyanatoaniline (4l)26. Yellow solid (19.6
o
1
mg, 46% yield); mp 87-88 C. H NMR (400 MHz, CDCl3)
δ 7.37 (d, J = 1.4 Hz, 1H), 7.33 (dd, J = 8.2, 1.9 Hz, 1H), 6.63
13
(d, J = 8.2 Hz, 1H), 3.87 (s, 2H), 2.15 (s, 3H). C{1H} NMR
2-(Furan-2-yl)-3-selenocyanatoimidazo[1,2-a]pyridine (4e)15.
Brown solid (44.9 mg, 79% yield); mp 178-179 oC. 1H NMR
(400 MHz, CDCl3) δ 8.39 (dt, J = 6.8, 1.0 Hz, 1H), 7.71 (d, J
= 9.0 Hz, 1H), 7.63 (dd, J = 1.7, 0.6 Hz, 1H), 7.45-7.40 (m,
1H), 7.18 (dd, J = 3.4, 0.6 Hz, 1H), 7.09 (td, J = 6.9, 1.1 Hz,
1H), 6.59 (dd, J = 3.4, 1.8 Hz, 1H). 13C{1H} NMR (101 MHz,
(101 MHz, CDCl3) δ 147.0, 137.1, 134.1, 124.0, 115.9, 107.1,
102.8, 17.2. HRMS (ESI) m/z: [M + H]+ Calcd for C8H9NSe+:
212.9926, Found: 212.9929.
2-Phenyl-3-thiocyanatoimidazo[1,2-a]pyridine
(5a)14a
.
o
Yellow solid (44.3 mg, 88% yield); mp 111-113 C.1H NMR
(400 MHz, CDCl3) δ 8.47 (dt, J = 6.8, 1.1 Hz, 1H), 8.18 –
8.00 (m, 2H), 7.78 (d, J = 9.0 Hz, 1H), 7.59 – 7.51 (m, 2H),
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 13
7.51 – 7.43 (m, 2H), 7.15 (td, J = 6.9, 1.1 Hz, 1H). 13C{1H} 3-iodo-2-phenylimidazo[1,2-a]pyridine (6)27. Yellow solid
(29.5 mg, 46% yield). 1H NMR (400 MHz, CDCl3) δ 8.18 (dt,
J = 6.9, 1.1 Hz, 1H), 8.10 – 8.03 (m, 2H), 7.60 (dt, J = 9.0, 1.0
Hz, 1H), 7.52 – 7.44 (m, 2H), 7.42 – 7.35 (m, 1H), 7.24 –
7.20 (m, 1H), 6.88 (td, J = 6.8, 1.1 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 148.1, 148.0, 133.6, 128.6, 128.38, 128.37, 126.5,
125.6, 117.6, 113.2, 59.6.
1
2
3
4
5
6
7
8
NMR (101 MHz, CDCl3) δ 153.1, 148.0, 132.0, 129.5, 128.84,
128.77, 128.0, 124.4, 118.3, 114.4, 108.1, 94.7.
2-(4-(tert-Butyl)phenyl)-3-thiocyanatoimidazo[1,2-
a]pyridine (5b). Yellow solid (49.4 mg, 81% yield); mp 129
o
– 130 C. 1H NMR (600 MHz, CDCl3) δ 8.44 (d, J = 6.8 Hz,
1H), 8.02 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 9.0 Hz, 1H), 7.56
(d, J = 8.4 Hz, 2H), 7.48 – 7.42 (m, 1H), 7.10 (t, J = 6.8 Hz,
1H), 1.39 (s, 9H). 13C{1H} NMR (151 MHz, CDCl3) δ 153.1,
152.7, 147.9, 129.1, 128.5, 127.9, 125.8, 124.4, 118.2, 114.3, 108.2,
94.3, 34.9, 31.3. HRMS (ESI) m/z: [M + H]+ Calcd for
C18H18N3S +: 308.1216, Found: 308.1217.
2-(3-Chlorophenyl)-3-thiocyanatoimidazo[1,2-a]pyridine
(5c). Yellow solid (33.7 mg, 59% yield); mp 152 – 153 oC. 1H
NMR (600 MHz, CDCl3) δ 8.46 (d, J = 6.8 Hz, 1H), 8.08 (s,
1H), 7.97 (dd, J = 7.1, 1.5 Hz, 1H), 7.77 (d, J = 9.0 Hz, 1H),
7.52 – 7.44 (m, 3H), 7.20 – 7.12 (m, 1H). 13C{1H} NMR (151
MHz, CDCl3) δ 151.5, 147.9, 134.9, 133.8, 130.0, 129.5, 128.8,
128.3, 126.8, 124.4, 118.4, 114.7, 107.7, 95.2. HRMS (ESI) m/z:
[M + H]+ Calcd for C14H9ClN3S +: 286.0200, Found:
286.0201.
Ethyl
3-((2-phenylimidazo[1,2-a]pyridin-3-
yl)selanyl)imidazo[1,2-a]pyridine-2-carboxylate (7). Light
o
1
yellow solid (9.0 mg, 20% yield); mp 151 - 152 C. H NMR
(600 MHz, CDCl3) δ 9.02 (d, J = 6.9 Hz, 1H), 8.05 (d, J = 7.3
Hz, 2H), 7.60 (dd, J = 13.1, 5.6 Hz, 3H), 7.55 (t, J = 8.5 Hz,
2H), 7.51 (d, J = 7.0 Hz, 1H), 7.30 – 7.21 (m, 2H), 7.17 – 7.07
(m, 1H), 6.88 (t, J = 6.8 Hz, 1H), 6.36 (t, J = 6.8 Hz, 1H),
4.60 (q, J = 7.1 Hz, 2H), 1.53 (t, J = 7.1 Hz, 3H). 13C{1H} NMR
(151 MHz, CDCl3) δ 163.5, 152.2, 147.6, 146.8, 139.4, 134.0,
129.8, 128.9, 128.6, 127.4, 127.2, 126.8, 126.4, 118.7, 117.4,
113.9, 113.2, 110.4, 102.2, 61.7, 14.5. 77Se NMR (76 MHz,
CDCl3) δ 21.1. HRMS (ESI) m/z: [M + H]+ Calcd for
C23H19N4O2Se+: 463.0668, Found: 463.0672.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3,3'-oxybis(2-phenylimidazo[1,2-a]pyridine) (8). Light
yellow solid (7.8 mg, 19% yield); mp 241 - 242 oC. 1H NMR
(600 MHz, CDCl3) δ 8.01 (d, J = 7.5 Hz, 4H), 7.59 (t, J = 7.4
Hz, 4H), 7.55 (dd, J = 14.3, 7.1 Hz, 4H), 7.49 (d, J = 8.9 Hz,
2H), 7.09 (t, J = 7.8 Hz, 2H), 6.34 (t, J = 6.8 Hz, 2H).
13C{1H} NMR (151 MHz, CDCl3) δ 151.6, 147.3, 134.1, 129.7,
128.7, 128.4, 126.3, 126.1, 117.3, 112.5, 103.8. HRMS (ESI) m/z:
[M + Na]+ Calcd for C26H18N4ONa+: 525.1373, Found:
425.1364.
3-Thiocyanato-2-(o-tolyl)imidazo[1,2-a]pyridine
(5d).
Yellow solid (31.3 mg, 60% yield); mp 141 – 142 oC. 1H NMR
(400 MHz, CDCl3) δ 8.45 (dt, J = 6.8, 1.0 Hz, 1H), 7.77 (dt, J
= 9.0, 1.0 Hz, 1H), 7.52 - 7.48 (m, 1H), 7.42 - 7.30 (m, 4H),
13
7.17 (td, J = 6.8, 1.0 Hz, 1H), 2.38 (s, 3H). C{1H} NMR (101
MHz, CDCl3) δ 154.9, 147.8, 137.6, 131.4, 130.72, 130.67, 129.4,
127.8, 125.7, 124.5, 118.4, 114.4, 108.1, 96.8, 20.2. HRMS (ESI)
+
m/z: [M + H]+ Calcd for C15H12N3S : 266.0746, Found:
266.0747.
ASSOCIATED CONTENT
Supporting Information
3-Thiocyanato-2-(thiophen-2-yl)imidazo[1,2-a]pyridine (5e).
o
1
Yellow solid (47.2 mg, 92% yield); mp 158 – 159 C. H
NMR (400 MHz, CDCl3) δ 8.39 (dt, J = 6.8, 1.1 Hz, 1H), 7.96
(dd, J = 3.7, 1.1 Hz, 1H), 7.72 (dt, J = 9.0, 1.0 Hz, 1H), 7.50
(dd, J = 5.1, 1.1 Hz, 1H), 7.47 – 7.43 (m, 1H), 7.20 (dd, J = 5.1,
The Supporting Information is available free of charge on the
ACS Publications website.
Experimental procedures and spectra data for 2-8 (PDF)
Singly-crystal X-ray diffraction data for compounds 2a (CIF)
3.7 Hz, 1H), 7.10 (td, J = 6.9, 1.1 Hz, 1H). C{1H} NMR (101
13
MHz, CDCl3) δ 148.0, 147.9, 134.7, 128.3, 128.2, 128.1, 127.7,
124.3, 118.0, 114.5, 107.5, 93.2. HRMS (ESI) m/z: [M + H]+
AUTHOR INFORMATION
Corresponding Author
+
Calcd for C12H8N3S2 : 258.0154, Found: 258.0155.
7-Chloro-2-phenyl-3-thiocyanatoimidazo[1,2-a]pyridine (5f).
Yellow solid (30.1 mg, 53% yield); mp 183 – 184 oC. 1H NMR
(400 MHz, CDCl3) δ 8.36 (dd, J = 7.2, 0.7 Hz, 1H), 8.09 –
7.96 (m, 2H), 7.76 (dd, J = 2.0, 0.7 Hz, 1H), 7.59 – 7.43 (m,
Email: zhuxinju@zzu.edu.cn (X.Z)
Email: mpsong@zzu.edu.cn (M.P.S)
3H), 7.12 (dd, J = 7.2, 2.0 Hz, 1H). C{1H} NMR (101 MHz,
13
Notes
The authors declare no competing financial interest.
CDCl3) δ 153.9, 147.7, 134.9, 131.5, 129.84, 128.79, 128.8, 124.7,
117.2, 116.0, 107.7, 95.3. HRMS (ESI) m/z: [M + H]+ Calcd
for C14H9ClN3S +: 286.0200, Found: 286.0199.
ACKNOWLEDGMENT
8-Methoxy-2-phenyl-3-thiocyanatoimidazo[1,2-a]pyridine
(5g). Yellow solid (25.9 mg, 46% yield); mp 198 – 199 oC.1H
NMR (400 MHz, CDCl3) δ 8.25 (dd, J = 7.5, 0.4 Hz, 1H),
8.09 – 7.96 (m, 2H), 7.57 – 7.49 (m, 2H), 7.47 (dt, J = 9.7,
4.4 Hz, 1H), 7.02 (d, J = 2.4 Hz, 1H), 6.81 (dd, J = 7.5, 2.5 Hz,
1H), 3.92 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 160.3,
153.3, 149.7, 132.1, 129.3, 128.7, 128.6, 124.7, 109.1, 108.5, 95.8,
92.9, 55.9. HRMS (ESI) m/z: [M + H]+ Calcd for
C15H12N3OS +: 282.0696, Found: 282.0699.
Financial support from the National Natural Science
Foundation of China (Grant Nos. 21672192, 21803059,
U1904212 and 21929101) is gratefully appreciated.
REFERENCES
(1) (a) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T.
Organoselenium and Organotellurium Compounds:
Toxicology and Pharmacology. Chem. Rev. 2004, 104, 6255.
(b) Weekley, C. M., Harris, H. H. Which form is that? The
importance of selenium speciation and metabolism in the
10
ACS Paragon Plus Environment

Page 11 of 13
The Journal of Organic Chemistry
prevention and treatment of disease. Chem. Soc. Rev, 2013, (5) (a) Castanheiro, T.; Suffert, J.; Donnard, M.; Gulea,
1
2
3
4
5
6
42, 8870. (c) Feng, M.; Tang, B.; Liang, S. H.; Jiang, X.
Sulfur Containing Scaffolds in Drugs: Synthesis and
Application in Medicinal Chemistry. Curr. Top. Med.
Chem. 2016, 16, 1200. (d) Zhang, C.; Zhu, X. Thieno[3,4-
b]thiophene-Based Novel Small-Molecule Optoelectronic
Materials. Acc. Chem. Res. 2017, 50, 1342.
M. Recent advances in the chemistry of organic
thiocyanates. Chem. Soc. Rev. 2016, 45, 494. (b) Pawliczek,
M.; Garve, L. K. B.; Werz, D. B. Activation of Aryl
Thiocyanates Followed by Aryne Insertion: Access to 1,2-
Thiobenzonitriles. Org. Lett. 2015, 17, 1716. (c)
Bayarmagnai, B.; Matheis, C.; Jouvin, K.; Goosen, L. J.
(2) (a) Pan, F.; Shi, Z.-J. Recent Advances in Transition-
Metal-Catalyzed C–S Activation: From Thioester to
(Hetero)aryl Thioether. ACS Catal. 2014, 4, 280. (b)
Modha, S. G.; Mehta, V. P.; Van der Eycken, E. V.
Transition metal-catalyzed C–C bond formation via C–S
bond cleavage: an overview. Chem. Soc. Rev. 2013, 42, 5042.
(c) Rathore, V.; Jose, C.; Kumar, S. Organoselenium small
molecules as catalysts for the oxidative functionalization
of organic molecules. New. J. Chem. 2019, 43, 8852. (d)
Verma, A.; Jana, S.; Prasad, C. D.; Yadav, A.; Kumar, S.
Organoselenium and DMAP co-catalysis: regioselective
Synthesis
of
Difluoromethyl
Thioethers
from
7
8
9
Difluoromethyl Trimethylsilane and Organothiocyanates
Generated In Situ. Angew. Chem. Int. Ed., 2015, 54, 5753.
(d) Jiang, H.; Yu, W.; Tang, X.; Li, J.; Wu, W. Copper-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Catalyzed
Aerobic
Oxidative
Regioselective
Thiocyanation of Aromatics and Heteroaromatics. J. Org.
Chem. 2017, 82, 9312. (e) Mukherjee, N.; Kundu, D.; Ranu,
B. C. Copper-Silver Dual Catalyzed Decyanative C-Se
Cross-Coupling. Adv. Synth. Catal. 2017, 359, 329.
(6) (a) Yang, H.; Duan, X.-H.; Zhao, J.-F.; Guo, L.-N.
Transition-Metal-Free
Thiocyanooxygenation of Olefinic Amides: A New Route
to SCN-Containing Heterocycles. Org. Lett. 2015, 17, 1998.
(b) Lin, Q.; Yang, W.; Yao, Y.; Chen, S.; Tan, Y.; Chen, D.;
Yang, D. Copper-Catalyzed Diastereoselective 1,2-
Difunctionalization of Oxabenzonorbornadienes Leading
to β-Thiocyanato Thioethers. Org. Lett. 2019, 21, 7244. (c)
Yang, S.-M.; He, T.-J.; Lin, D.-Z.; Huang, J.-M.
Electrosynthesis of (E)-Vinyl Thiocyanates from Cinnamic
Acids via Decarboxylative Coupling Reaction. Org. Lett.
2019, 21, 1958. (d) Meng, F.; Zhang, H.; He, H.; Xu, N.;
Fang, Q.; Guo, K.; Cao, S.; Shi, Y.; Zhu, Y. Copper-
Tandem
Radical
synthesis
of
medium-sized
halolactones
and
bromooxepanes from unactivated alkenes. Chem.
Commun. 2016, 52, 4179.
(3) (a) Shen, C.; Zhang, P.; Sun, Q.; Bai, S.; Hor, T. S. A.;
Liu, X. Recent advances in C–S bond formation via C–H
bond functionalization and decarboxylation. Chem. Soc.
Rev. 2015, 44, 291. (b) Ivanova, A.; Arsenyan, P. Rise of
diselenides: Recent advances in the synthesis of
Heteroarylselenides. Coord. Chem. Rev. 2018, 370, 55. (c)
Martins, G. M.; Meirinho, A. G.; Ahmed, N.; Braga, A. L.;
Mendes, S. R. Recent Advances in Electrochemical
Chalcogen
(S/Se)-Functionalization
of
Organic
Catalyzed
Domino
Cyclization/Thiocyanation
of
Molecules. ChemElectroChem 2019, 6, 5928. (d)
Mampuys, P.; McElroy, G. R.; Clark, J. H.; Orru, R. V. A.;
Maes, B. U. W. Thiosulfonates as Emerging Reactants:
Synthesis and Applications. Adv. Synth. Catal. 2020, 362,
3. (e) Guin, S.; Deb, A.; Dolui, P.; Chakraborty, S.; Singh, V.
K.; Maiti, D. Promoting Highly Diastereoselective γ-C−H
Chalcogenation of α-Amino Acids and Aliphatic
Carboxylic Acids. ACS Catal. 2018, 8, 2664.
(4) (a) Gandeepan, P.; Koeller, J.; Ackermann, L.
Expedient C–H Chalcogenation of Indolines and Indoles
by Positional-Selective Copper Catalysis. ACS Catal. 2017,
7, 1030. (b) Prasad, C. D.; Sattar, M.; Kumar, S. Transition-
Metal-Free Selective Oxidative C(sp3)−S/Se Coupling of
Oxindoles, Tetralone, and Arylacetamides: Synthesis of
Unsymmetrical Organochalcogenides. Org. Lett. 2017, 19,
774. (c) Wang, H.; Li, Y.; Lu, Q.; Yu, M.; Bai, X.; Wang, S.;
Cong, H.; Zhang, H.; Lei, A. Oxidation-Induced β-
Selective C–H Bond Functionalization: Thiolation and
Selenation of N-Heterocycles. ACS Catal. 2019, 9, 1888.
(d) Rathore, V.; Kumar, S. Visible-light-induced metal and
reagent-free oxidative coupling of sp2 C–H bonds with
organodichalcogenides: synthesis of 3-organochalcogenyl
indoles. Green Chem. 2019, 21, 2670. (e) Jana, S.; Verma,
A.; Rathore, V.; Kumar, S. Synthesis of Novel C2-
Symmetric Sulfur-Based Catalysts: Asymmetric Formation
of Halo- and Seleno-Functionalized Normal- and
MediumSized Rings. Synlett. 2019, 30, 1667.
Unactivated Olefins: Access to SCN-Containing
Pyrazolines. Adv. Synth. Catal. 2020, 362, 248.
(7) (a) Jiang, G.; Zhu, C.; Li, J.; Wu, W.; Jiang, H. Silver-
Catalyzed Regio- and Stereoselective Thiocyanation of
Haloalkynes: Access to (Z)-Vinyl Thiocyanates. Adv. Synth.
Catal. 2017, 359, 1208. (b) Dwivedi, V.; Rajesh, M.; Kumar,
R.; Kant, R.; Reddy, M. S. A stereoselective thiocyanate
conjugate addition to electron deficient alkynes and
concomitant cyclization to N,S-heterocycles. Chem.
Commun. 2017, 53, 11060. (c) Wu, C.; Lu, L.-H.; Peng, A.-Z.;
Jia, G.-K.; Peng, C.; Cao, Z.; Tang, Z.; He, W.-M.; Xu, X.
Ultrasound-promoted Brønsted acid ionic liquid-
catalyzed hydrothiocyanation of activated alkynes under
minimal solvent conditions. Green Chem. 2018, 20, 3683.
(d) Lu, L.-H.; Zhou, S.-J.; Sun, M.; Chen, J.-L.; Xia, W.; Yu,
X.; Xu, X.; He, W.-M. Metal- and Solvent-Free Ultrasonic
Multicomponent
Vinylthiocyanates. ACS Sustainable Chem. Eng. 2019, 7,
1574. (e) Zeng, X.; Chen, B.; Lu, Z.; Hammond, G. B.; Xu, B.
Homogeneous
Hydrothiocyanation of Haloalkynes. Org. Lett. 2019, 21,
2772.
Synthesis
of
(Z)-β-Iodo
and
Nanoparticle
Gold-Catalyzed
(8) (a) Fan, W.; Yang, Q.; Xu, F.; Li, P. A Visible-Light-
Promoted Aerobic Metal-Free C-3 Thiocyanation of
Indoles. J. Org. Chem. 2014, 79, 10588. (b) Dey, A.; Hajra,
A. Potassium Persulfate-Mediated Thiocyanation of 2H-
Indazole under Iron-Catalysis. Adv. Synth. Catal. 2019, 361,
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 13
842; (c) Li, G.; Yan, Q.; Gong, X.; Dou, X.; Yang, D. Functionalizations. Chem. Rec. 2019, 19, 2105. (c) Tashrifi,
1
2
3
4
5
6
7
8
Photocatalyst-Free Regioselective C–H Thiocyanation of
4-Anilinocoumarins under Visible Light. ACS Sustainable
Chem. Eng. 2019, 7, 14009.
Z.; Mohammadi-Khanaposhtani, M.; Larijani, B.; Mahdavi,
M. C3-Functionalization of Imidazo[1,2-a]pyridines. Eur. J.
Org. Chem. 2020, 2020, 269. For recent papers, please see:
(d) Jin, S.; Xie, B.; Lin, S.; Min, C.; Deng, R.; Yan, Z. Metal-
Free Site-Specific Hydroxyalkylation of Imidazo[1,2-
a]pyridines with Alcohols through Radical Reaction. Org.
Lett. 2019, 21, 3436. (e) Singsardar, M.; Mondal, S.; Laru, S.;
(9) (a) Yuan, P.-F.; Zhang, Q.-B.; Jin, X.-L.; Lei, W.-L.;
Wu, L.-Z.; Liu, Q. Visible-light-promoted aerobic metal-
free aminothiocyanation of activated ketones. Green
Chem. 2018, 20, 5464. (b) Liang, S.; Zeng, C.-C.; Tian, H.-
Y.; Sun, B.-G.; Luo, X.-G.; Ren, F.-Z. Redox Active Sodium
Iodide/Recyclable Heterogeneous Solid Acid: An Efficient
Dual Catalytic System for Electrochemically Oxidative α-
C−H Thiocyanation and Sulfenylation of Ketones. Adv.
Synth. Catal. 2018, 360, 1444. (c) Mao, X.; Ni, J.; Xu, B.;
Ding, C. K2S2O8-promoted direct thiocyanation of
pyrazolin-5-ones with ammonium thiocyanate at room
temperature. Org. Chem. Front. 2020, 7, 350.
Hajra,
A.
Organophotoredox-Catalyzed
C(sp2)–H
Difluoromethylenephosphonation of Imidazoheterocycles.
Org. Lett. 2019, 21, 5606. (f) Li, B.; Shen, N.; Yang, Y.;
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Zhang,
X.;
Fan,
X.
Synthesis
via
of
Rh(iii)-
naphtho[1’,2’:4,5]imidazo[1,2-a]pyridines
catalyzed C-H functionalization of 2-arylimidazo[1,2-
a]pyridines with cyclic 2-diazo-1,3-diketones featuring
with a ring opening and reannulation. Org. Chem. Front.
2020, 7, 919.
(10) (a) Sun, K.; Lv, Y.; Chen, Y.; Zhou, T.; Xing, Y.; Wang,
X. A novel metal-free method for the selenocyanation of
aromatic ketones to afford α-carbonyl selenocyanates.
Org. Biomol. Chem. 2017, 15, 4464. (b) Maity, P.; Paroi, B.;
Ranu, B. C. Transition-Metal-Free Iodine Catalyzed
Selenocayanation of Styrenyl Bromides and an Easy
Access to Benzoselenophenes via Intermediacy of Styrenyl
Selenocyanate. Org. Lett. 2017, 19, 5748. (c) Chen, J.;
Wang, T.; Wang, T.; Lin, A.; Yao, H.; Xu, J. Copper-
catalyzed C5-selective thio/selenocyanation of 8-
aminoquinolines. Org. Chem. Front. 2017, 4, 130. (d) Wu,
C.; Xiao, H.-J.; Wang, S.-W.; Tang, M.-S.; Tang, Z.-L.; Xia,
W.; Li, W.-F.; Cao, Z.; W.-M. Natural Deep Eutectic
Solvent-Catalyzed Selenocyanation of Activated Alkynes
via an Intermolecular H-Bonding Activation Process. ACS
Sustainable Chem. Eng. 2019, 7, 2169. (e) Ghosh, P.;
Chhetri, G.; Nandi, A. K.; Sarkar, S.; Saha, T.; Das, S.
Creation of thio and selenocyanate derivatives of 4-
quinolone via regioselective C–H bond functionalization
under ambient conditions. New J. Chem. 2019, 43, 10959.
(f) He, D.; Yao, J.; Ma, B.; Wei, J.; . Hao, G; Tuo, X.; Guo, S.;
Fu, Z.; Cai, H. An electrochemical method for
deborylative seleno/thiocyanation of arylboronic acids
under catalyst- and oxidant-free conditions. Green Chem.
2020, 22, 1559.
(11) (a) Enguehard-Gueiffier, C.; Gueiffier, A. Recent
Progress in the Pharmacology of Imidazo[1,2-a]pyridines.
Mini-Rev. Med. Chem. 2007, 7, 888. (b) Stasyuk, A. J.;
Banasiewicz, M.; Cyrański, M. K.; Gryko, D. T.
Imidazo[1,2-a]pyridines Susceptible to Excited State
Intramolecular Proton Transfer: One-Pot Synthesis via an
Ortoleva–King Reaction. J. Org. Chem. 2012, 77, 5552. (c)
Cao, X.-N.; Wan, X.-M.; Yang, F.-L.; Li, K.; Hao, X.-Q.;
Shao, T.; Zhu, X.; Song. M.-P, NNN Pincer Ru(II)-
Complex-Catalyzed α-Alkylation of Ketones with Alcohols.
J. Org. Chem. 2018, 83, 3657.
(13) (a) Sun, P.; Yang, D.; Wei, W.; Jiang, M.; Wang, Z.;
Zhang, L.; Zhang, H.; Zhang, Z.; Wang, Y.; Wang, H.
Visible light-induced C–H sulfenylation using sulfinic
acids. Green Chem. 2017, 19, 4785. (b) Zhang, J.-R.; Liao,
Y.-Y.; Deng, J.-C.; Feng, K.-Y.; Zhang, M.; Ning, Y.-Y.; Lin,
Z.-W.; Tang, R.-Y. Oxidative dual C–H thiolation of
imidazopyridines with ethers or alkanes using elemental
sulphur. Chem. Commun. 2017, 53, 7784. (c) Rahaman, R.;
Das, S.; Barman, P. Visible-light-induced regioselective
sulfenylation of imidazopyridines with thiols under
transition metal-free conditions. Green Chem. 2018, 20, 141.
(d) Rafique, J.; Saba, S.; Franco, M. S.; Bettanin, L.;
Schneider, A. R.; Silva, L. T.; Braga, A. L. Direct, Metal-
free C(sp2)−H Chalcogenation of Indoles and
Imidazopyridines with Dichalcogenides Catalysed by KIO3.
Chem. Eur. J. 2018, 24, 4173. (e) Jiang, N.; Fang, Y.; Fang, Y.;
Wang, S.-Y.; Ji, S.-J. Iodine-promoted one pot reaction of
pyridin-2-amine
selenosulfonate:
with
synthesis
arylmethyl
of
ketone
3-(alkylselanyl)-2-
and
arylimidazo[1,2-a]pyridine under transition-metal free
conditions. Org. Chem. Front. 2019, 6, 654. (f) Wen, J.;
Niu, C.; Yan, K.; Cheng, X.; Gong, R.; Li, M.; Guo, Y.; Yang,
J.; Wang, H. Electrochemical-induced regioselective C-3
thiomethylation of imidazopyridines via
a
three-
component cross-coupling strategy. Green Chem. 2020, 22,
1129.
(14) (a) Yang, D.; Yan, K.; Wei, W.; Li, G.; Lu, S.; Zhao, C.;
Tian, L.; Wang, H. Catalyst-Free Regioselective C-3
Thiocyanation of Imidazopyridines. J. Org. Chem. 2015, 80,
11073. (b) Mitra, S.; Ghosh, M.; Mishra, S.; Hajra, A. Metal-
Free Thiocyanation of Imidazoheterocycles through
Visible Light Photoredox Catalysis. J. Org. Chem. 2015, 80,
8275. (c) Zhang, H.; Wei, Q.; Wei, S.; Qu, J.; Wang, B.
Highly Efficient and Practical Thiocyanation of
Imidazopyridines Using an N-Chlorosuccinimide/NaSCN
Combination. Eur. J. Org. Chem. 2016, 2016, 3373.
(12) For reviews, please see: (a) Bagdi, A. K.; Santra, S.;
Monir, K.; Hajra, A. Synthesis of imidazo[1,2-a]pyridines: a
decade update. Chem. Commun. 2015, 51, 1555. (b) Yu, Y.;
Su, Z.; Cao, H. Strategies for Synthesis of Imidazo[1,2-
a]pyridine Derivatives: Carbene Transformations or C−H
(15) Redon, S.; Kosso, A. R. O.; Broggi, J.; Vanelle, P. Easy
and efficient selenocyanation of imidazoheterocycles
using Triselenodicyanide. Tetrahedron Lett. 2017, 58, 2771.
(16) (a) Simon, M.-O.; Li, C.-J. Green chemistry oriented
12
ACS Paragon Plus Environment

Page 13 of 13
The Journal of Organic Chemistry
organic synthesis in water. Chem. Soc. Rev. 2012, 41, 1415.
57, 4138.
1
2
3
4
5
6
7
8
(b) Zeng, H.; Wang, Z.; Li, C.-J. Two-in-One Strategy for
Palladium-Catalyzed C−H Functionalization in Water.
Angew. Chem. Int. Ed. 2019, 58, 2859. (c) Li, J.; Tang, W.;
Ren, D.; Xu, J.; Yang, Z. Iridium-catalysed highly selective
reduction–elimination of steroidal 4-en-3-ones to 3,5-
dienes in water. Green Chem. 2019, 21, 2088. (d) Liu, X-C.;
Chen, X.-L.; Liu, Y.; Sun, K.; Peng, Y.-Y.; Qu, L.-B.; Yu, B.
Visible-Light-Induced Metal-Free Synthesis of 2-
Phosphorylated Thioflavones in Water. ChemSusChem
2020, 13, 298.
(17) (a) Yang, F.-L.; Tian, S.-K. Iodine-Catalyzed
Regioselective Sulfenylation of Indoles with Sulfonyl
Hydrazides. Angew. Chem. Int. Ed. 2013, 52, 4929. (b)
Geng, X.; Wang, C.; Zhao, P.; Zhou, Y.; Wu, Y.-D.; Wu, A.-
X. Iodine-Promoted N–H/α,β-C(sp3)-Trifunctionalization
(22) Ji, X.-M.; Zhou, S.-J.; Chen, F.; Zhang, X.-G.; Tang, R.-
Y. Direct Sulfenylation of Imidazoheterocycles with
Disulfides in an Iodine–Hydrogen Peroxide System.
Synthesis 2015, 47, 659.
(23) (a) Muniraj, N.; Dhineshkumar, J.; Prabhu, K. R. N-
Iodosuccinimide Catalyzed Oxidative Selenocyanation
and
Thiocyanation
of
Electron
Rich
Arenes.
ChemistrySelect 2016, 5, 1033. (b) Zhao, P.; Wu, X.; Geng,
X.; Wang, C.; Zhou, Y.; Wu, Y.-D.; Wu, A.-X. I2/PhI(OAc)2
Copromoted Amination Reaction: Synthesis of α-
Dicarbonylsulfoximine Derivatives by Incorporating an
Intact Dimethyl Sulfoxide. J. Org. Chem. 2019, 84, 8322.
(24) (a) Rodríguez, J. C.; Maldonado, R. A.; G, R. -G.;
Cervantes, E. D.; de la Cruz, F. N. Microwave-assisted
synthesis and luminescent activity of imidazo[1,2-
a]pyridine derivatives. J Heterocyclic Chem. 2020, 57, 2279.
(b) Pericherla, K.; Kaswan, P.; Pandey, K.; Kumar, A.
Recent Developments in the Synthesis of Imidazo[1,2-
a]pyridines. Synthesis 2015, 47, 887.
(25) Zhang, X.; Wang, C.; Jiang, H.; Sun, L. A low-cost
electrochemical thio- and selenocyanation strategy for
electron-rich arenes under catalyst- and oxidant-free
conditions. RSC Adv. 2018, 8, 22042.
(26) Kachanov, A.; Slabko, O. Y.; Baranova, O. V.; Shilova,
E. V.; Kaminskii, V. A. Triselenium dicyanide from
malononitrile and selenium dioxide. One-pot synthesis of
selenocyanates. Tetrahedron Lett. 2004, 45, 4461.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
of
l-Proline:
Access
to
3,4-
Dihydrobenzo[b][1,7]naphthyridines via Consecutive
Decarboxylation/Ring Opening/Dicyclization. Org. Lett.
2019, 21, 4939. (c) Gui, Q.-W.; He, X.; Wang, W.; Zhou, H.;
Dong, Y.; Wang, N.; Tang, J.-X.; Cao, Z.; He, W.-M. The
clean preparation of multisubstituted pyrroles under
metal- and solvent-free conditions. Green Chem. 2020, 22,
118.
(18) (a) Lu, S.; Zhu, X.; Li, K.; Guo, Y-J.; Wang, M-D.;
Zhao, X-M.; Hao, X-Q.; Song, M-P. Reactivity of p-
Toluenesulfonylmethyl Isocyanide: Iron-Involved C–H
Tosylmethylation of Imidazopyridines in Nontoxic Media.
J. Org. Chem. 2016, 81, 8370. (b) Guo, Y.-J.; Lu, S.; Tian, L.-
L.; Huang, E.-L.; Hao, X.-Q.; Zhu, X.; Shao, T.; Song, M.-P.
Iodine-Mediated Difunctionalization of Imidazopyridines
with Sodium Sulfinates: Synthesis of Sulfones and Sulfides.
J. Org. Chem. 2018, 83, 338. (c) Zhi, C.; Wang, Q.; Liu, S.;
Xue, Y.; Shi, L.; Zhu, X.; Hao, X.-Q.; Song, M.-P. Cu-
Catalyzed Direct C7 Sulfonylation of Indolines with
Arylsulfonyl Chlorides. J. Org. Chem. 2020, 85, 1022. (d)
Tian, L.-L.; Lu, S.; Zhang, Z.-H.; Huang, E.-L.; Yan, H.-T.;
Zhu, X.; Hao, X.-Q.; Song, M.-P. Copper-Catalyzed
(27) Mondal, S.; Samanta, S.; Mukta Singsardar, M.;
Mishra, S.; Mitra, S.; Hajra, A. Zwitterionic-Type Molten
Salt Catalyzed Iodination in Water: Synthesis of
Iodoimidazoheterocycles. Synthesis. 2016, 48, 4009.
Double
Thiolation
to
Access
Sulfur-Bridged
Imidazopyridines with Isothiocyanate. J. Org. Chem. 2019,
84, 5213.
(19) (a) Lu, S.; Tian, L-L.; Cui, T.-W.; Zhu, Y.-S.; Zhu, X.;
Hao, X.-Q.; Song, M.-P. Copper-Mediated C–H Amination
of Imidazopyridines with N-Fluorobenzenesulfonimide. J.
Org. Chem. 2018, 83, 13991. (b) Zhao, X-M.; Huang, E.-L.;
Zhu, Y.-S.; Li, J.; Song, B.; Zhu, X.; Hao, X.-Q. Oxidative
sulfonamidomethylation of imidazopyridines utilizing
methanol as the main C1 source. Org. Biomol. Chem. 2019,
17, 4869.
(20) Wang, T.; Chen, J.; Wang, J.; Xu, S.; Lin, A.; Yao, H.;
Jiang, S.; Xu, J. Cobalt-catalyzed carbon–sulfur/selenium
bond formation: synthesis of benzo[b]thio/selenophene-
fused imidazo[1,2-a]pyridines. Org. Biomol. Chem. 2018,
16, 3721.
(21) Kumar, R. U.; Reddy, K. H. V.; Satish, G.; Swapna, K.;
Nageswar, Y. V. D. Metal free synthesis of diaryl selenides
using SeO2 as a selenium Source. Tetrahedron Lett. 2016,
13
ACS Paragon Plus Environment