PhI(OAc) 2 -Mediated Regioselective Synthesis of 5-Guanidino-1,2,4-thiadiazoles and 1,2,4-Triazolo[1,5- a ]pyridines via Oxidative N-S and N-N Bond Formation

Article abstract of DOI:10.1055/s-0037-1611854

An effective and expeditious approach for the construction of biologically important 5-guanidino-1,2,4-thiadiazole and 1,2,4-triazolo[1,5- a ]pyridine derivatives has been developed. This new protocol involves the phenyliodine(III) diacetate [PhI(OAc)

Full text of DOI:10.1055/s-0037-1611854

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–K
paper
A
en
T. Nagaraju et al.
Paper
Synthesis
PhI(OAc)2-Mediated Regioselective Synthesis of 5-Guanidino-
1,2,4-thiadiazoles and 1,2,4-Triazolo[1,5-a]pyridines via Oxidative
N–S and N–N Bond Formation
Tumula Nagarajua,b
S
NH2
R2
Palakodety Radha Krishna*a
Balasubramanian Sridharc
Nakka Mangarao*a
0
0
0
0-0
0
0
2-3
2
8
7-3
4
7
7
R3
R2
N
N
NH
R1
N
NH2
N
S
N
N
R1
R3
H
R1
N
EtO
N
PhI(OAc)2
AcOH, MeCN, rt
H2N
N
PhI(OAc)2
MeCN, rt
R2
N–N and C–N bond
7–10 h, 20 examples
78–94% yield
N–S and C–N bond
3–5 h, 18 examples
78–92% yield
a Organic Synthesis and Process Chemistry Division, CSIR-Indian
Institute of Chemical Technology, Hyderabad 500007, India
mangarao@csiriict.in
metal-free, regioselectivity, high efficiency,
wide substrate scope, insensitive to air and moisture,
gram-scale
b Academy of Scientific and Innovative Research (AcSIR), New
Delhi 110025, India
c Center for X-ray Crystallography, CSIR-Indian Institute of
Chemical Technology, Hyderabad 500007, India
Received: 15.02.2019
O
N
Accepted after revision: 24.04.2019
Published online: 08.07.2019
DOI: 10.1055/s-0037-1611854; Art ID: ss-2019-t0101-op
N
H
S
N
S
N
O
N
H2N
N
N
N
Abstract An effective and expeditious approach for the construction
of biologically important 5-guanidino-1,2,4-thiadiazole and 1,2,4-tri-
azolo[1,5-a]pyridine derivatives has been developed. This new protocol
involves the phenyliodine(III) diacetate [PhI(OAc)2]-mediated oxidative
cyclization of thioureas/2-aminopyridines and imidates via N–S and N–
N bond formation at ambient temperature. This method furnishes the
versatile 5-guanidino-1,2,4-thiadiazoles and 1,2,4-triazolo[1,5-a]pyri-
dines in a scalable manner with high efficiency and excellent regioselec-
tivity.
O
F
F
F
O
O
F
N
Cefozopran (antibiotic activity)
N
N
N
NH2
O
F
F
Me
OH
Sitagliptin (antidiabetic activity)
N
N
N
CN
Key words metal-free, regioselectivity, high efficiency, wide sub-
strate scope, insensitivity to air and moisture, 5-guanidino-1,2,4-thiadi-
azoles, 1,2,4-triazolo[1,5-a]pyridines, gram scale
F
N
S
N
N
N
Me
NC
Me
F
Ravuconazole (antifungal activity)
Heterocyclic chemistry is the most demanding and am-
ply rewarding field, and by far heterocyclic scaffolds are the
largest class in organic chemistry. Synthetic organic chem-
ists made significant progresses in discovering and develop-
ing wide range of heterocyclic compounds for the benefit of
mankind. Among these, nitrogen-rich heterocycles are the
most important class of compounds with wide applications
and biological activities.1 Due to their importance and suc-
cess, N-containing heterocycles are key targets for the syn-
thesis, and there is a demand for the construction of new
approaches that provide access to novel and underdevel-
oped nitrogen-rich compounds.
1,2,4-Thiadiazoles and 1,2,4-triazoles are considered as
very significant nitrogen-based heterocyclic scaffolds due
to their important biological activities which can be used as
key skeletons in many pharmaceuticals with anticancer,2
antifungal,3 antibacterial,4 and anti-inflammatory activi-
ties.5 In addition, they are also available in biologically ac-
tive drugs such as Cefozopran,6 Sitagliptin,7 Ravuconazole,8
and Anastrozole9 (Figure 1).
Me
Me
CN
Anastrozole (prevents breast cancer)
Figure 1 Selected biologically active 1,2,4-thiadiazole and 1,2,4-tri-
azole derivatives
Due to their broad applications in medicinal and phar-
maceutical areas, the syntheses of 1,2,4-thiadiazoles and
1,2,4-triazoles have attracted great attention. The most
common pathways for the synthesis of 1,2,4-thiadiazoles
and 1,2,4-triazoles mainly involves the simple oxidative di-
merization of primary thioamides using various oxidants10
and coupling of carboxylic acids or their derivatives with
amidrazones, followed by cyclodehydration,11 respectively.
On the other hand, hypervalent iodine(III) reagents are
highly dominant non-metal oxidants due to their low toxic-
ity, easy accessibility, high reactivity, and environmentally
benign nature.12 In particular, hypervalent iodine(III) re-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
T. Nagaraju et al.
Paper
Synthesis
agents of phenyliodine(III) diacetate (PIDA) and phenylio-
dine(III) bis(trifluoroacetate) (PIFA) have been employed in
the construction of C–C, C–X, and N–X (X = N,O,S) bond for-
mation protocols.13–15 Among these methods, carbon–car-
bon and carbon–heteroatom bond constructions have been
intensively explored. A careful literature survey reveals that
there are only a few reports providing the formation of het-
erocyclic compounds through the heteroatom–heteroatom
bond formation approach. In particular, the construction of
heterocycles through the hypervalent iodine(III)-mediated
N–N and N–S bond forming reactions were very limited, as
shown in Scheme 1.16
improved yields of product 3a (entries 11, 12), and the use
of 2 equivalents of oxidant gave the best result (entry 12).
However, with a further increase of PhI(OAc)2 from 2 to 2.5
equivalents, the yield of 3a did not increase (entry 13).
Thus, the established conditions are: 1 equivalent of 1a and
2 equivalents of 2a with 2 equivalents of PhI(OAc)2 in the
presence of acetonitrile (entry 12).
Table 1 Optimization of Reaction Conditionsa
Ph
S
N
S
NH
N
oxidant
Ph
Ph
N
NH2
EtO
Ph
N
solvent, rt
H2N
N
H
Ph
Lee:
2a
1a
3a
N
R
N
N
PhI(OAc)2
N
N
R
R
R
Entry
Oxidant (equiv)
Solvent
Yield (%)b
NHTs
1
2
PhI(OAc)2 (1)
PhI(OAc)2 (1)
PhI(OAc)2 (1)
PhI(OAc)2 (1)
PhI(OAc)2 (1)
PhI(OAc)2 (1)
CH2Cl2
CHCl3
DMF
18
10
15
28
40
trace
25
20
15
NR
72
90
90
Muthusubramanian:
NH
S
N
S
3
PhI(OCOCF3)2
R
R
R
N
R
N
N
N
4
DMSO
MeCN
PhCl
H
H
H
5
Our previous work:
6
R
R
N
NH
S
N
S
7
PhI(OCOCF3)2 (1)
PhIO (1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
CN
PhI(OAc)2
R
R
N
R
N
NH
R
R
N
8
R
9
I2 (1)
Scheme 1 Previous methods for the construction of heterocycles
through iodine(III)-mediated N–S and N–N bond formation
10
11
12
13
TBAI (1)
PhI(OAc)2 (1.5)
PhI(OAc)2 (2)
PhI(OAc)2 (2.5)
In a continuation of our previous efforts for the con-
struction of biologically important heterocyclic com-
pounds,17 we present here efficient and regioselective N–S
and N–N bond formations from imidates18 for the synthesis
of 5-guanidino-1,2,4-thiadiazoles and 1,2,4-triazolo[1,5-
a]pyridines using PhI(OAc)2.
a Reaction conditions: 1a (2 mmol, 1 equiv), 2a (4 mmol, 2 equiv), catalyst
(1–2.5 equiv), and solvent (1 mL) at rt for 3 to 5 h.
b Isolated yield. NR: No reaction.
Under the optimal reaction conditions (Table 1, entry
12), we explored the generality and functional group com-
patibility of this transformation for the synthesis of 5-guan-
idino-1,2,4-thiadiazoles and the results are summarized in
Scheme 2. A wide variety of imidates with various substitu-
ents were explored. As anticipated, all the imidates gave the
corresponding 5-guanidino-1,2,4-thiadiazoles in good to
high yields. Phenylimidates with electron-donating groups
like methyl and methoxy at para- and meta-positions af-
forded the corresponding products 3b, 3c, and 3f in good to
excellent isolated yields. Conversely, the reaction progress
with halogen substituent on phenylimidates such as F and
Cl at para, meta, and ortho positions afforded the products
3d, 3e, 3g, and 3h in moderate to good yields. The structure
of product 3e was unambiguously secured by the X-ray dif-
fraction analysis (Figure 2). Gratifyingly, ortho-substituted
electron-withdrawing phenylimidate afforded the yield
similar to that of para-subsitituted phenylimidate. In addi-
tion, the heteroimidate like thiophene-2-carbimidate gave
3i in 86% yield. Notably, an alicyclic imidate such as cyclo-
Initially the phenylimidate, ethyl benzenecarboximidate
(1a; 1.0 equiv), N-phenylthiourea (2a; 2.0 equiv), and
PhI(OAc)2 (1.0 equiv) in CH2Cl2 at room temperature were
selected as a model reaction to explore and screening the
reaction conditions. At first, the desired product 5-guanidi-
no-1,2,4-thiadiazole 3a was formed in very low yield (Table
1, entry 1). To enhance the yield of the product, we have
studied several solvents such as CHCl3, DMF, DMSO, MeCN,
and PhCl and the results revealed that MeCN was superior
to other solvents (entries 2–6). Next, we extended our in-
vestigation by studying various oxidants like PhI(OCOCF3)2,
PhIO, I2, and TBAI (entries 7–10). The stronger oxidant
PhI(OCOCF3)2 could not provide a better yield of the product
3a (entry 7) and PhIO was found to be less potent under the
studied conditions (entry 8). Oxidants like I2 and TBAI were
also inefficient to provide the desired product (entries 9,
10). Having acceptable oxidant for the synthesis of guanidi-
no thiadiazoles, we further focused on the quantity of
PhI(OAc)2. Raising the equivalance of PhI(OAc)2 resulted in
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

C
T. Nagaraju et al.
Paper
Synthesis
hexyl imidate could also be compatible with the reaction to
deliver the corresponding product 3j in 82% yield. In the
case of aliphatic propylimidate, the corresponding product
3k was obtained in moderate yield. To extend the scope of
the substrates and limitations of the reaction, we further
studied various N-phenylthioureas with phenylimidate,
which proceeded proficiently to afford the corresponding
5-guanidino-1,2,4-thiadiazoles in good to excellent yields.
As mentioned in Scheme 2, all N-phenylthiourea substrates
bearing electron-donating substituents such as Me and
OMe at para, meta, and ortho positions of the phenyl ring
gave the corresponding products 3l, 3o, and 3p in good to
high yields. Electron-withdrawing substrate like Cl on the
aryl ring gave the desired product in very good yield
(Scheme 2, → 3m). N-Phenylthiourea with strong electron-
withdrawing group like NO2 generated the corresponding
thiadiazole 3n in 80% yield. It should be observed that the
oxidative cyclization was satisfyingly conducted in gram
scale without any complication (Scheme 2, → 3a).
Figure 2 X-ray crystal structures of 3e, 3q, and 5b (see Supporting In-
formation for details)
ture of products 3q in 40% yield along with 3a and 3p in
25% and 15% yield, respectively, were obtained. This indi-
cates that a cross-dimerization of N-phenylthioureas takes
place to furnish the corresponding product 3q (confirmed
by X-ray crystal structure analysis, Figure 2) along with
homo-dimerized products 3a and 3p (Scheme 3a). The re-
gioisomeric 3q, namely 3q′ was not observed mainly due
the electronic factors of electron-donating ortho-methoxy
group on the phenyl, which prefers to stay substituted to
nitrogen atom of the 1,2,4-thiadiazole ring as it facilitates
its formation, which is not the case with 3q′. To substanti-
ate this, another experiment was conducted with a sub-
strate possessing an electron-withdrawing substrate like
2m (1 equiv) and 2p (1 equiv) with 1a (1 equiv) under the
same reaction conditions (Scheme 3b). We isolated similar
set of products, 3r in 35% yield along with 3m and 3p in 20%
Further, we wanted to check if this protocol works
equally well when a mixture of thioureas were used. Thus,
when the reaction was conducted between 1 equivalent of
2a and 1 equivalent of 2p with 1 equivalent of phenylimi-
date 1a under the established reaction conditions, a mix-
R2
N
NH
N
S
S
PhI(OAc)2
MeCN, rt
R1
R2
EtO
R1
H2N
N
R2
N
N
NH2
H
1
2
3
N
N
Ph
N
S
S
Ph
N
N
N
Ph
N
S
X
N
N
N
H2N
N
H2N
N
H2N
X
Ph
F
Ph
Ph
3h, 83%
3a, X = H, 90% (85%)
3b, X = Me, 92%
3c, X = OMe, 91%
3d, X = F, 87%
3f, X = Me, 85%
3g, X = Cl, 87%
3e, X = Cl, 90%
N
Ph
N
S
N
S
S
Ph
Ph
N
S
N
N
N
N
N
N
N
H2N
N
H2N
H2N
Ph
Ph
Ph
3i, 86%
3j, 82%
3k, 83%
X
N
OMe
N
N
S
N
S
N
Ph
Ph
Me
N
N
N
N
S
H2N
N
N
H2N
Ph
N
H2N
MeO
Me
X
3l, X = OMe, 88%
3m, X = Cl, 90%
3n, X = NO2, 80%
3o, 85%
3p, 78%
Scheme 2 Synthesis of 5-guanidino-1,2,4-thiadiazoles. Reagents and conditions: 1 (2 mmol, 1 equiv), 2 (4 mmol, 2 equiv), PIDA (2 equiv), and MeCN
(1 mL) at rt for 3 to 5 h. Isolated yields are shown. The yield shown in parentheses for 3a is for the reaction conducted on a gram scale.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

D
T. Nagaraju et al.
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Synthesis
Ph
OMe
N
S
N
Ph
NH
S
S
PhI(OAc)2
MeCN, rt
N
N
S
H2N
N
N
N
3a
3p
Ph
Ph
EtO
Ph
MeO
N
NH2
a)
N
NH2
N
H2N
H
H
OMe
Ph
2p
1a
15%
2a
25%
3q, 40%
3q', 0%
OMe
Cl
N
S
N
N
N
S
N
Ph
Ph
Cl
b)
NH
Ph
N
H2N
S
S
N
H2N
N
PhI(OAc)2
MeCN, rt
3m
3p
MeO
EtO
N
H
NH2
N
NH2
H
OMe
Cl
2p
15%
1a
20%
3r, 35%
2m
3r', 0%
Scheme 3 Synthesis of cross-dimerization products of 5-guanidino-1,2,4-thiadiazoles
and 15%, respectively. This clearly states that the donating-
group containing aryl moiety prefers to remain as N-sub-
stituent of 1,2,4-thiadiazole ring, while the withdrawing-
group-bearing aryl group decorates the guanidino nitrogen.
The aforementioned results prompted us to further ex-
tend the scope of this practical approach by replacing N-
phenylthioureas 2 with 2-aminopyridines 4 under the stan-
dard conditions to prepare 1,2,4-triazolo[1,5-a]pyridines.
For this the equivalents of PhI(OAc)2 used were varied and
AcOH was used as an additive to enhance the reaction rate.
Finally, we arrived at the optimum reaction conditions as: 1
equivalent of 1, 1 equivalent of 4 with 1 equivalent of
PhI(OAc)2 in the presence of 1 equivalent of the additive
AcOH in acetonitrile at room temperature. As shown in
Scheme 4, this protocol tolerates a variety of phenylimi-
dates with 2-aminopyridines. No significant substituent ef-
fect was observed, and excellent yields were obtained for
phenylimidates having both electron-donating and elec-
NH2
NH
N
PhI(OAc)2
R1
R3
R3
N
N
AcOH
MeCN, rt
EtO
R1
N
4
1
5
X
N
N
N
5a, X = H, 92% (87%)
5b, X = Me, 94%
5c, X = OMe, 90%
5d, X = F, 85%
5e, X = Cl, 91%
5f, X = CF3, 90%
X
N
N
N
5g, X = Me, 91%
5h, X = Cl, 89%
5i, X = Br, 82%
5j, X = NO2, 78%
F
N
N
N
N
S
N
N
N
N
N
5k, 78%
5l, 80%
5m, 86%
N
N
N
N
N
N
N
N
N
5n, 80%
5o, 82%
5p, 81%
X
Me
Me
N
N
N
Me
Cl
N
N
N
N
N
N
5q, X = Me, 92%
5r, X = Cl, 85%
5s, 92%
5t, 94%
Scheme 4 Synthesis of 1,2,4-triazolo[1,5-a]pyridines. Reagents and conditions: 1 (2 mmol, 1 equiv), 4 (2 mmol, 1 equiv), PIDA (1 equiv), AcOH (1 equiv),
and MeCN (1 mL) at rt for 7 to 10 h. Isolated yields are shown. The yield shown in parentheses for 5a is for the reaction conducted on a gram scale.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

E
T. Nagaraju et al.
Paper
Synthesis
ant of both electron-donating group such as methyl (→ 5q)
and electron-withdrawing group such as halogen (→ 5r).
Reactions of halogen-containing substrates negatively af-
fected the reaction yields compared to the methyl-contain-
ing substrate, which was due to the relatively low nucleo-
philicity of the pyridines affected by the halogens (→ 5q–t).
Here also we synthesized compound 5a in gram scale suc-
cessfully. Compound 5b has been unambiguously deter-
mined by X-ray diffraction analysis (Figure 2).
To gain a better understanding of the reaction mecha-
nism, a series of control experiments were carried out un-
der the standard reaction conditions (Scheme 5). When the
control experiment was carried out with a radical scaven-
ger such as TEMPO (2,2,6,6-tetramethylpiperdine-1-oxide),
it did not influence the reaction rate and outcome of the
product yield, which suggests a favoring of ionic mecha-
nism (Scheme 5a). When the phenylimidate 1a and 2-ami-
nopyridine 4a undergo reaction in the presence of acetic
acid in the absence of PhI(OAc)2, the intermediate N-(pyri-
din-2-yl)imidamide (F) (Scheme 5b) was obtained. This in-
termediate F reacts with PhI(OAc)2 to give our desired prod-
uct 5a in 92% yield (Scheme 5c).
Ph
N
S
S
NH
N
PhI(OAc)2
Ph
Ph
(a)
N
H
NH2
N
EtO
Ph
H2N
N
TEMPO
MeCN, rt
Ph
1a
2a
3a, 85%
H
N
Ph
NH
NH2
AcOH
N
NH
(b)
(c)
EtO
Ph
N
MeCN, rt, 7h
F, 87%
4a
1a
H
N
Ph
N
PhI(OAc)2
Ph
N
N
NH
MeCN, rt, 2h
N
F
5a, 92%
Scheme 5 Control experiments
tron-withdrawing substituents with 2-aminopyridines. It is
worth noting that heterocyclic substituent such as thienyl
ring (→ 5l) could also well survive the process with 80%
yield. This methodology worked equally well with alicyclic
imidates such as cyclohexyl and cyclopropyl, and good
yields were observed (→ 5m and 5n). Fortunately, the reac-
tion worked equally well with aliphatic imidates, including
propyl and isopropyl, which gave corresponding 1,2,4-tri-
azolo[1,5-a]pyridines in good yields (→ 5o and 5p). The
heterocyclic ring of 2-aminopyridine was found to be toler-
On the basis of existing literature reports19,20 and our
experimental results, a plausible reaction mechanism for
the formation of 5-guanidino-1,2,4-thiadiazoles and 1,2,4-
triazolo[1,5-a]pyridines is proposed (Scheme 6). Initially,
2a undergoes reaction with PhI(OAc)2 to afford polyvalent
iodine intermediate A, which undergoes iodobenzene elim-
NH
Ph
I
NH
PhHN
S
S
PhI(OAc)2
NH2
– 2 AcOH
2 AcOH
PhHN
S
S
NHPh
a)
– PhI
NH
– S
– AcOH
2
PhHN
2
B
A
2a
AcO
S
OAc
I
AcO
Ph
NH
Ph
I
NH
S
NH
NH
NH
NH
S
EtO
Ph
1a
PhI(OAc)2
– AcOH
PhHN
N
N
Ph
AcOH
NH2
PhHN
N
N
H
Ph
PhHN
N
– AcOH
EtOH
Ph
Ph
Ph
D
C
E
N
N
N
Ph
S
S
N
HN
Ph
Ph
N
– PhI
N
N
H2N
PhHN
– AcOH
Ph
Ph
3a
Ph
OAc
OAc
Ph
NH
NH2
I
I
N
NH
N
HN
OAc
AcOH
b)
EtO
Ph
N
N
Ph
N
Ph
– AcOH
H
1a
F
4a
G
H
N
N
N
N
Ph
– AcO–
– PhI
N
– H+
N
Ph
H
5a
Scheme 6 Proposed reaction mechanism
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

F
T. Nagaraju et al.
Paper
Synthesis
ination and dimerizes to form 1,6-diphenyldithioformami-
dine B. Then the intermediate B eliminates sulfur and forms
amidinothiourea C. Next, intermediate C reacts with 1a to
give the thiourea intermediate D, which undergoes reaction
with second equivalent of PhI(OAc)2 to form the intermedi-
ate E, which on intramolecular nucleophilic attack of the
NH group on sulfur followed by isomerization affords the
desired guanidinothiadiazole 3a (Scheme 6a). Whereas 1a
condensed with 4a to afford the intermediate N-(pyridin-2-
yl)imidamide F in the presence of acetic acid, the interme-
diate F reacts with PhI(OAc)2 to generate the intermediate G
with the release of acetic acid and then intramolecular
nucleophilic attack of the nitrogen atom of the pyridine
ring takes place to give ammonium ion H, which affords the
required product 5a after rearomatization through the
elimination of a proton (Scheme 6b).
In summary, we could develop a novel and convenient
approach for the construction of 5-guanidino-1,2,4-thiadi-
azoles and 1,2,4-triazolo[1,5-a]pyridines under mild condi-
tions through oxidative N–S and N–N bond formation from
thioureas/2-aminopyridines and imidates for the first time.
The use of environmentally benign PhI(OAc)2 reagent
makes this protocol green and highly practical. Moreover,
the metal-free nature of the protocol, its regioselectivity
and high functional group tolerance, the mild reaction con-
ditions, and the scalability are all attractive features of this
method.
(E)-1,2-Diphenyl-1-(3-phenyl-1,2,4-thiadiazol-5-yl)guanidine (3a)
Eluent: Hexane/EtOAc (92:8); white solid; yield: 672 mg (90%); mp
198–200 °C.
1H NMR (500 MHz, CDCl3):  = 8.04–8.03 (m, 2 H), 7.63–7.51 (m, 5 H),
7.41–7.32 (m, 5 H), 7.14–7.10 (m, 3 H), 4.41 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 177.1, 166.2, 145.7, 137.9, 133.7,
130.2, 129.7, 129.6, 129.4, 129.3, 128.3, 127.7, 123.7, 122.8.
HRMS (ESI): m/z [M + H]+ calcd for C21H18N5S: 372.1277; found:
372.1281.
Scale-Up Reaction for 3a
A mixture of ethyl benzenecarboximidate (1a; 0.894 g, 6 mmol), N-
phenylthiourea (2a; 1.98 g, 13 mmol), and PhI(OAc)2 (4.18 g, 13
mmol) in MeCN (1 mL) was stirred at rt. After completion of the reac-
tion as monitored by TLC, the reaction mixture was quenched with
sat. aq NaHCO3. The organic and aqueous layers were then separated
and the aqueous layer was extracted with EtOAc (2 ×). The combined
organic layers were dried (anhyd Na2SO4) and concentrated under re-
duced pressure. The crude product was purified by silica gel column
chromatography using EtOAc/hexane as eluent to afford 3a; yield:
1.8921g (85%).
(E)-1,2-Diphenyl-1-[3-(p-tolyl)-1,2,4-thiadiazol-5-yl]guanidine
(3b)
Eluent: Hexane/EtOAc (92:8); white solid; yield: 651 mg (92%); mp
205–207 °C.
1H NMR (400 MHz, CDCl3):  = 7.92 (d, J = 8.1 Hz, 2 H), 7.63–7.51 (m, 5
H), 7.41–7.37 (m, 2 H), 7.14–7.09 (m, 5 H), 4.41 (s, 2 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 177.0, 166.3, 145.8, 145.7, 139.4,
137.9, 131.1, 130.2, 129.7, 129.6, 129.3, 128.9, 127.6, 123.7, 122.8,
21.4.
Chemicals and all solvents were obtained from commercial suppliers
and used without further purification. 1H NMR spectra were mea-
sured on Bruker Avance-300, Varian Unity-400 MHz and Avance New-
500 MHz and 13C NMR spectra were measured with Varian Unity-300
MHz (75 MHz), Varian Unity-400 MHz (100 MHz) and Avance New-
500 MHz (125 MHz), as specified and referred to TMS as the internal
standard. Chemical shifts () are given in ppm and J values are given
in hertz (Hz). High-resolution mass spectra (HRMS) were performed
on a high-resolution magnetic sector mass spectrometer. TLC analysis
was performed on Merck silica gel 60 F254 plates. Column chromatog-
raphy was performed on silica gel (100–200 mesh) from Merck. Melt-
ing points were measured using melting point apparatus and are un-
corrected. Evaporation of solvents was performed at reduced pres-
sure, using a rotary vacuum evaporator.
HRMS (ESI): m/z [M + H]+ calcd for C22H20N5S: 386.1433; found:
386.1440.
(E)-1-[3-(4-Methoxyphenyl)-1,2,4-thiadiazol-5-yl]-1,2-diphenyl-
guanidine (3c)
Eluent: Hexane/EtOAc (90:10); white solid; yield: 611 mg (91%); mp
202–204 °C.
1H NMR (400 MHz, CDCl3):  = 7.97 (d, J = 8.7 Hz, 2 H), 7.63–7.49 (m, 5
H), 7.41–7.37 (m, 2 H), 7.13–7.09 (m, 3 H), 6.84 (d, J = 8.7 Hz, 2 H),
4.41 (s, 2 H), 3.79 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 177.0, 166.0, 160.6, 145.8, 145.6,
137.9, 130.2, 129.7, 129.6, 129.3, 129.2, 126.8, 123.6, 122.8, 113.5,
55.3.
HRMS (ESI): m/z [M + H]+ calcd for C22H20N5OS: 402.1383; found:
402.1384.
5-Guanidino-1,2,4-thiadiazoles 3a–r; General Procedure
A mixture of imidate 1 (2 mmol), N-phenylthiourea 2 (4 mmol), and
PhI(OAc)2 (4 mmol) in MeCN (1 mL) was stirred at rt. After completion
of the reaction as monitored by TLC, the reaction mixture was
quenched with sat. aq NaHCO3. The organic and aqueous layers were
then separated and the aqueous layer was extracted with EtOAc (2 ×).
The combined organic layers were dried (anhyd Na2SO4) and concen-
trated under reduced pressure. The crude product was purified by sil-
ica gel column chromatography using EtOAc/hexane as eluent to af-
ford the corresponding product 3a–r.
(E)-1-[3-(4-Fluorophenyl)-1,2,4-thiadiazol-5-yl]-1,2-diphenyl-
guanidine (3d)
Eluent: Hexane/EtOAc (92:8); white solid; yield: 607 mg (87%); mp
199–201 °C.
1H NMR (400 MHz, CDCl3):  = 8.04–7.99 (m, 2 H), 7.64–7.50 (m, 5 H),
7.41–7.37 (m, 2 H), 7.14–7.09 (m, 3 H), 7.03–6.97 (m, 2 H), 4.42 (s, 2
H).
13C NMR (100 MHz, CDCl3):  = 177.2, 165.2, 164.8, 162.4, 145.6,
137.8, 130.3, 130.0, 129.7, 129.6, 129.3, 123.8, 122.8, 115.2 (d, J = 21.6
Hz).
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HRMS (ESI): m/z [M + H]+ calcd for C21H17FN5S: 390.1183; found:
1H NMR (300 MHz, DMSO-d6):  = 7.65–7.54 (m, 6 H), 7.40–7.35 (m, 3
390.1187.
H), 7.10–7.03 (m, 4 H), 5.85 (s, 2 H).
13C NMR (75 MHz, DMSO-d6):  = 176.6, 160.4, 146.4, 145.4, 137.5,
137.4, 129.9, 129.3, 128.2, 127.7, 127.1, 122.8.
(E)-1-[3-(4-Chlorophenyl)-1,2,4-thiadiazol-5-yl]-1,2-diphenyl-
guanidine (3e)
HRMS (ESI): m/z [M + H]+ calcd for C19H16N5S2: 378.0841; found:
378.0851.
Eluent: Hexane/EtOAc (92:8); white solid; yield: 597 mg (90%); mp
220–222 °C.
1H NMR (400 MHz, CDCl3):  = 7.97 (d, J = 8.5 Hz, 2 H), 7.64–7.51 (m, 5
H), 7.42–7.38 (m, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.15–7.09 (m, 3 H),
4.42 (s, 2 H).
(E)-1-(3-Cyclohexyl-1,2,4-thiadiazol-5-yl)-1,2-diphenylguanidine
(3j)
Eluent: Hexane/EtOAc (90:10); white solid; yield: 597 mg (82%); mp
175–177 °C.
13C NMR (125 MHz, CDCl3):  = 177.2, 165.1, 145.6, 137.8, 135.3,
132.2, 130.3, 129.7, 129.2, 129.0, 128.4, 123.8, 122.8;
HRMS (ESI): m/z [M + H]+ calcd for C21H17ClN5S: 406.0887; found:
406.0892.
1H NMR (500 MHz, CDCl3):  = 7.59–7.56 (m, 2 H), 7.54–7.51 (m, 1 H),
7.47–7.44 (m, 2 H), 7.38–7.35 (m, 2 H), 7.11–7.08 (m, 1 H), 7.06–7.04
(m, 2 H), 4.38 (s, 2 H), 2.67 (tt, J = 11.6, 3.5 Hz, 1 H), 1.94–1.91 (m, 2
H), 1.74–1.71 (m, 2 H), 1.64–1.61 (m, 2 H), 1.49–1.41 (m, 2 H), 1.32–
1.26 (m, 2 H).
(E)-1,2-Diphenyl-1-[3-(m-tolyl)-1,2,4-thiadiazol-5-yl]guanidine
(3f)
13C NMR (100 MHz, CDCl3):  = 176.7, 174.4, 146.0, 145.8, 138.1,
130.2, 129.6, 129.5, 129.3, 123.5, 122.7, 41.9, 31.5, 26.1, 26.0.
HRMS (ESI): m/z [M + H]+ calcd for C21H24N5S: 378.1746; found:
Eluent: Hexane/EtOAc (92:8); white solid; yield: 602 mg (85%); mp
181–183 °C.
1H NMR (400 MHz, CDCl3):  = 7.88 (s, 1 H), 7.81 (d, J = 7.7 Hz, 1 H),
7.64–7.52 (m, 5 H), 7.42–7.38 (m, 2 H), 7.23–7.19 (m, 1 H), 7.15–7.10
(m, 4 H), 4.42 (s, 2 H), 2.34 (s, 3 H).
378.1751.
(E)-1,2-Diphenyl-1-(3-propyl-1,2,4-thiadiazol-5-yl)guanidine (3k)
13C NMR (100 MHz, CDCl3):  = 177.1, 166.4, 145.7, 137.9, 133.6,
130.2, 129.7, 129.6, 129.3, 128.2, 128.1, 125.0, 123.7, 122.8, 21.4.
Eluent: Hexane/EtOAc (90:10); white solid; yield: 729 mg (83%); mp
186–188 °C.
HRMS (ESI): m/z [M + H]+ calcd for C22H20N5S: 386.1433; found:
386.1440.
1H NMR (400 MHz, CDCl3):  = 7.60–7.49 (m, 3 H), 7.46–7.43 (m, 2 H),
7.39–7.34 (m, 2 H), 7.12–7.05 (m, 3 H), 4.37 (s, 2 H), 2.65–2.62 (m, 2
H), 1.72–1.62 (m, 2 H), 0.89 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 176.9, 170.5, 145.7, 137.9, 130.3,
(E)-1-[3-(3-Chlorophenyl)-1,2,4-thiadiazol-5-yl]-1,2-diphenyl-
guanidine (3g)
129.7, 129.2, 123.6, 122.8, 35.2, 21.4, 13.8.
HRMS (ESI): m/z [M + H]+ calcd for C18H20N5S: 338.1433; found:
338.1436.
Eluent: Hexane/EtOAc (92:8); white solid; yield: 576 mg (87%); mp
209–211 °C.
1H NMR (500 MHz, CDCl3):  = 8.02 (s, 1 H), 7.92 (d, J = 7.5 Hz, 1 H),
7.64–7.51 (m, 5 H), 7.41–7.38 (m, 2 H), 7.30–7.24 (m, 2 H), 7.15–7.10
(m, 3 H), 4.42 (s, 2 H).
(E)-1,2-Bis(4-methoxyphenyl)-1-(3-phenyl-1,2,4-thiadiazol-5-
yl)guanidine (3l)
13C NMR (100 MHz, CDCl3):  = 177.3, 164.8, 145.7, 137.7, 135.4,
134.2, 130.3, 129.8, 129.7, 129.5, 129.4, 129.2, 127.7, 125.8, 123.8,
122.8.
HRMS (ESI): m/z [M + H]+ calcd for C21H17ClN5S: 406.0887; found:
406.0901.
Eluent: Hexane/EtOAc (88:12); white solid; yield: 763 mg (88%); mp
202–204 °C.
1H NMR (400 MHz, CDCl3):  = 8.07–8.04 (m, 2 H), 7.43–7.40 (m, 2 H),
7.34–7.33 (m, 3 H), 7.10–7.02 (m, 4 H), 6.95–6.93 (m, 2 H), 4.42 (s, 2
H), 3.91 (s, 3 H), 3.81 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 177.3, 166.1, 160.1, 156.1, 146.2,
138.8, 133.8, 130.4, 129.4, 128.2, 127.7, 123.6, 115.3, 115.0, 55.64,
55.60.
(E)-1-[3-(2-Fluorophenyl)-1,2,4-thiadiazol-5-yl]-1,2-diphenyl-
guanidine (3h)
HRMS (ESI): m/z [M + H]+ calcd for C23H22N5O2S: 432.1488; found:
432.1484.
Eluent: Hexane/EtOAc (92:8); white solid; yield: 579 mg (83%); mp
207–209 °C.
1H NMR (500 MHz, CDCl3):  = 7.88–7.85 (m, 1 H), 7.62–7.59 (m, 2 H),
7.55–7.51 (m, 3 H), 7.41–7.38 (m, 2 H), 7.14–7.06 (m, 6 H), 4.43 (s, 2
H).
(E)-1,2-Bis(4-chlorophenyl)-1-(3-phenyl-1,2,4-thiadiazol-5-
yl)guanidine (3m)
13C NMR (100 MHz, CDCl3):  = 176.6, 162.5, 162.0, 159.5, 145.6,
137.8, 131.5, 130.8, 130.7, 130.3, 129.76, 129.72, 129.2, 123.7, 122.8,
118.9, 116.5 (d, J = 22.1 Hz).
HRMS (ESI): m/z [M + H]+ calcd for C21H17FN5S: 390.1183; found:
390.1187.
Eluent: Hexane/EtOAc (88:12); white solid; yield: 797 mg (90%); mp
237–239 °C.
1H NMR (400 MHz, DMSO-d6):  = 7.91–7.89 (m, 2 H), 7.67 (d, J = 8.7
Hz, 2 H), 7.59 (d, J = 8.7 Hz, 2 H), 7.40–7.37 (m, 5 H), 7.06 (d, J = 8.6 Hz,
2 H), 6.19 (s, 2 H).
13C NMR (75 MHz, DMSO-d6):  = 176.8, 164.7, 147.0, 144.7, 136.5,
133.7, 133.1, 131.3, 129.9, 129.6, 129.0, 128.5, 127.0, 126.6, 124.6.
(E)-1,2-Diphenyl-1-[3-(thiophen-2-yl)-1,2,4-thiadiazol-5-yl]guan-
idine (3i)
HRMS (ESI): m/z [M + H]+ calcd for C21H16Cl2N5S: 440.0498; found:
440.0509.
Eluent: Hexane/EtOAc (90:10); white solid; yield: 627 mg (86%); mp
230–232 °C.
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Synthesis
(E)-1,2-Bis(4-nitrophenyl)-1-(3-phenyl-1,2,4-thiadiazol-5-
yl)guanidine (3n)
1H NMR (400 MHz, CDCl3):  = 8.04–8.02 (m, 2 H), 7.56–7.52 (m, 1 H),
7.46 (dd, J = 7.7, 1.6 Hz, 1 H), 7.36–7.31 (m, 5 H), 7.18–7.13 (m, 2 H),
7.05 (d, J = 8.6 Hz, 2 H), 4.43 (s, 2 H), 3.81 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 176.9, 166.3, 155.9, 146.2, 144.6,
133.8, 131.4, 130.8, 129.6, 129.3, 128.7, 128.2, 127.7, 126.3, 124.2,
121.5, 113.0, 56.1.
Eluent: Hexane/EtOAc (85:15); yellow solid; yield: 742 mg (80%); mp
248–250 °C.
1H NMR (300 MHz, DMSO-d6):  = 8.48 (d, J = 8.7 Hz, 2 H), 8.25 (d, J =
8.8 Hz, 2 H), 7.95–7.90 (m, 4 H), 7.45–7.37 (m, 3 H), 7.28 (d, J = 8.8 Hz,
2 H), 6.74 (s, 2 H).
HRMS (ESI): m/z [M + H]+ calcd for C22H19ClN5OS: 436.0993; found:
13C NMR (100 MHz, DMSO-d6):  = 177.2, 165.5, 153.6, 148.2, 148.0,
436.1002.
143.6, 142.6, 133.3, 131.8, 130.3, 129.1, 127.6, 125.6, 124.1.
1,2,4-Triazolo[1,5-a]pyridines 5a–t; General Procedure
HRMS (ESI): m/z [M + H]+ calcd for C21H16N7O4S: 462.0979; found:
A mixture of imidate 1 (2 mmol), 2-aminopyridine 4 (2 mmol),
PhI(OAc)2 (2 mmol), and AcOH (2 mmol) in MeCN (1 mL) was stirred
at rt. After completion of the reaction as monitored by TLC, the reac-
tion mixture was quenched with sat. aq NaHCO3. The organic and
aqueous layers were then separated and the aqueous layer was ex-
tracted with EtOAc (2 ×). The combined organic layers were dried (an-
hyd Na2SO4) and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography using EtO-
Ac/hexane as eluent to afford the corresponding product 5a–t.
462.0987.
(E)-1-(3-Phenyl-1,2,4-thiadiazol-5-yl)-1,2-di-(m-tolyl)guanidine
(3o)
Eluent: Hexane/EtOAc (85:15); white solid; yield: 682 mg (85%); mp
181–183 °C.
1H NMR (400 MHz, CDCl3):  = 8.05–8.02 (m, 2 H), 7.50–7.46 (m, 1 H),
7.38–7.24 (m, 7 H), 6.94–6.88 (m, 3 H), 4.41 (s, 2 H), 2.45 (s, 3 H), 2.37
(s, 3 H).
13C NMR (100 MHz, CDCl3):  = 177.1, 166.1, 145.7, 140.4, 139.6,
137.8, 133.8, 130.4, 129.9, 129.6, 129.5, 129.4, 128.3, 127.7, 126.2,
124.5, 123.5, 119.7, 21.5, 21.4.
HRMS (ESI): m/z [M + H]+ calcd for C23H22N5S: 400.1590; found:
400.1593.
N-(Pyridin-2-yl)benzimidamide (F)20
Eluent: hexane/EtOAc (70:30); white solid; yield: 345 mg (87%); mp
96–98 °C.
1H NMR (400 MHz, CDCl3):  = 8.33 (dd, J = 4.9, 1.4 Hz, 1 H), 7.92–7.91
(m, 2 H), 7.67–7.63 (m, 1 H), 7.49–7.43 (m, 3 H), 7.29 (d, J = 8.2 Hz, 1
H), 6.95–6.92 (m, 1 H).
(E)-1,2-Bis(2-methoxyphenyl)-1-(3-phenyl-1,2,4-thiadiazol-5-
yl)guanidine (3p)
13C NMR (125 MHz, CDCl3):  = 162.7, 159.2, 145.9, 137.5, 137.3,
130.6, 128.6, 126.9, 122.3, 117.9.
HRMS (ESI): m/z [M + H]+ calcd for C12H12N3: 198.1025; found:
198.1031.
Eluent: Hexane/EtOAc (85:15); white solid; yield: 676 mg (78%); mp
195–197 °C.
1H NMR (400 MHz, CDCl3):  = 8.04–8.02 (m, 2 H), 7.52–7.47 (m, 2 H),
7.34–7.30 (m, 3 H), 7.16–7.07 (m, 4 H), 7.02–6.97 (m, 2 H), 4.39 (s, 2
H), 3.84 (s, 3 H), 3.80 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 172.4, 161.3, 151.2, 146.8, 141.2,
130.2, 129.3, 126.4, 126.1, 124.5, 123.4, 123.0, 121.9, 120.2, 119.7,
117.1, 116.7, 108.4, 108.3, 51.6, 51.3.
2-Phenyl[1,2,4]triazolo[1,5-a]pyridine (5a)20
Eluent: Hexane/EtOAc (86:14); white solid; yield: 361 mg (92%); mp
136–138 °C.
1H NMR (400 MHz, CDCl3):  = 8.60 (d, J = 6.8 Hz, 1 H), 8.31–8.27 (m, 2
H), 7.76 (d, J = 8.9 Hz, 1 H), 7.53–7.46 (m, 4 H), 7.02–6.98 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 164.2, 151.7, 130.8, 130.1, 129.5,
128.7, 128.3, 127.3, 116.4, 113.6.
HRMS (ESI): m/z [M + H]+ calcd for C23H22N5O2S: 432.1488; found:
432.1481.
HRMS (ESI): m/z [M + H]+ calcd for C12H10N3: 196.0869; found:
196.0865.
(E)-1-(2-Methoxyphenyl)-2-phenyl-1-(3-phenyl-1,2,4-thiadiazol-
5-yl)guanidine (3q)
Eluent: Hexane/EtOAc (85:15); white solid; yield: 322 mg (40%); mp
190–191 °C.
1H NMR (500 MHz, CDCl3):  = 8.05–8.02 (m, 2 H), 7.55–7.51 (m, 1 H),
7.47 (dd, J = 7.7, 1.5 Hz, 1 H), 7.40–7.37 (m, 2 H), 7.34–7.31 (m, 3 H),
7.17–7.10 (m, 5 H), 4.42 (s, 2 H), 3.81 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 176.9, 166.2, 155.9, 145.9, 133.9,
131.3, 130.8, 130.1, 129.6, 129.3, 128.2, 127.7, 126.4, 123.5, 122.9,
121.5, 113.0, 56.1.
Scale-Up Reaction for 5a
A mixture of ethyl benzenecarboximidate (1a; 0.894 g, 6 mmol), 2-
aminopyridine 4a (0.56 g, 6 mmol), PhI(OAc)2 (1.93 g, 6 mmol), and
AcOH (0.36 g, 6 mmol) in MeCN (1 mL) was stirred at rt. After comple-
tion of the reaction as monitored by TLC, the reaction mixture was
quenched with sat. aq NaHCO3. The organic and aqueous layers were
then separated and the aqueous layer was extracted with EtOAc (2 ×).
The combined organic layers were dried (anhyd Na2SO4) and concen-
trated under reduced pressure. The crude product was purified by sil-
ica gel column chromatography using EtOAc/hexane as eluent to af-
ford corresponding product 5a; yield: 1.0106g (87%).
HRMS (ESI): m/z [M + H]+ calcd for C22H20N5OS: 402.1383; found:
402.1396.
(E)-2-(4-Chlorophenyl)-1-(2-methoxyphenyl)-1-(3-phenyl-1,2,4-
thiadiazol-5-yl)guanidine (3r)
2-(p-Tolyl)[1,2,4]triazolo[1,5-a]pyridine (5b)20
Eluent: Hexane/EtOAc (85:15); white solid; yield: 306 mg (35%); mp
213–215 °C.
Eluent: Hexane/EtOAc (85:15); white solid; yield: 395 mg (94%); mp
170–172 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

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T. Nagaraju et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 8.56 (d, J = 6.8 Hz, 1 H), 8.18 (d, J = 8.2
Hz, 2 H), 7.72 (d, J = 8.9 Hz, 1 H), 7.47–7.43 (m, 1 H), 7.30 (d, J = 8.0 Hz,
2 H), 6.96–6.92 (m, 1 H), 2.41 (s, 3 H).
1H NMR (400 MHz, CDCl3):  = 8.59 (d, J = 6.8 Hz, 1 H), 8.13–8.08 (m, 2
H), 7.75 (d, J = 8.9 Hz, 1 H), 7.51–7.47 (m, 1 H), 7.41–7.37 (m, 1 H),
7.29 (s, 1 H), 7.00–6.97 (m, 1 H), 2.45 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 164.3, 151.6, 140.2, 129.45, 129.42,
13C NMR (125 MHz, CDCl3):  = 164.3, 151.6, 138.4, 130.9, 130.6,
128.2, 127.9, 127.2, 116.2, 113.4, 21.5.
129.5, 128.6, 128.3, 127.9, 124.4, 116.3, 113.6, 21.4.
HRMS (ESI): m/z [M + H]+ calcd for C13H12N3: 210.1025; found:
HRMS (ESI): m/z [M + H]+ calcd for C13H12N3: 210.1025; found:
210.1022.
210.1027.
2-(4-Methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridine (5c)20
2-(3-Chlorophenyl)[1,2,4]triazolo[1,5-a]pyridine (5h)20
Eluent: Hexane/EtOAc (80:20); white solid; yield: 339 mg (90%); mp
140–142 °C.
Eluent: Hexane/EtOAc (84:16); white solid; yield: 333 mg (89%); mp
186–188 °C.
1H NMR (500 MHz, CDCl3):  = 8.57 (d, J = 6.8 Hz, 1 H), 8.24–8.21 (m, 2
H), 7.72 (d, J = 8.9 Hz, 1 H), 7.50–7.47 (m, 1 H), 7.03–7.00 (m, 2 H),
6.99–6.96 (m, 1 H), 3.88 (s, 3 H).
1H NMR (500 MHz, CDCl3):  = 8.58–8.56 (m, 1 H), 8.29–8.28 (m, 1 H),
8.17–8.15 (m, 1 H), 7.75–7.72 (m, 1 H), 7.52–7.47 (m, 1 H), 7.42–7.38
(m, 2 H), 7.02–6.98 (m, 1 H).
13C NMR (125 MHz, CDCl3):  = 164.1, 161.2, 151.7, 129.4, 128.8,
13C NMR (125 MHz, CDCl3):  = 162.9, 151.6, 134.7, 132.6, 130.0,
128.2, 123.4, 116.1, 114.1, 113.3, 55.3.
129.9, 129.7, 128.3, 127.4, 125.3, 116.5, 113.9.
HRMS (ESI): m/z [M + H]+ calcd for C13H12N3O: 226.0974; found:
HRMS (ESI): m/z [M + H]+ calcd for C12H9ClN3: 230.0479; found:
226.0970.
230.0481.
2-(4-Fluorophenyl)[1,2,4]triazolo[1,5-a]pyridine (5d)20
2-(3-Bromophenyl)[1,2,4]triazolo[1,5-a]pyridine (5i)
Eluent: Hexane/EtOAc (86:14); white solid; yield: 325 mg (85%); mp
177–179 °C.
Eluent: Hexane/EtOAc (83:17); white solid; yield: 295 mg (82%); mp
201–203 °C.
1H NMR (500 MHz, CDCl3):  = 8.59 (d, J = 6.8 Hz, 1 H), 8.30–8.26 (m, 2
H), 7.75 (d, J = 8.9 Hz, 1 H), 7.53–7.49 (m, 1 H), 7.20–7.16 (m, 2 H),
7.02–6.99 (m, 1 H).
1H NMR (400 MHz, CDCl3):  = 8.60 (d, J = 6.8 Hz, 1 H), 8.47–8.46 (m, 1
H), 8.22 (d, J = 7.8 Hz, 1 H), 7.77 (d, J = 9.0 Hz, 1 H), 7.61–7.52 (m, 2 H),
7.39–7.35 (m, 1 H), 7.06–7.02 (m, 1 H).
13C NMR (125 MHz, CDCl3):  = 164.2 (d, J = 213.5 Hz), 163.1, 151.7,
129.5 (d, J = 39.3 Hz), 129.2, 128.3, 127.0 (d, J = 2.7 Hz), 116.4, 115.7
(d, J = 21.8 Hz), 113.7.
13C NMR (100 MHz, CDCl3):  = 162.8, 151.7, 133.0, 132.8, 130.3,
130.2, 129.8, 128.4, 125.8, 122.9, 116.6, 113.9.
HRMS (ESI): m/z [M + H]+ calcd for C12H9BrN3: 273.9974; found:
273.9971.
HRMS (ESI): m/z [M + H]+ calcd for C12H9FN3: 214.0775; found:
214.0771.
2-(3-Nitrophenyl)[1,2,4]triazolo[1,5-a]pyridine (5j)
2-(4-Chlorophenyl)[1,2,4]triazolo[1,5-a]pyridine (5e)20
Eluent: Hexane/EtOAc (80:20); white solid; yield: 289 mg (78%); mp
280–282 °C.
1H NMR (400 MHz, CDCl3):  = 9.16–9.15 (m, 1 H), 8.65–8.61 (m, 2 H),
8.33–8.31 (m, 1 H), 7.81 (d, J = 9.0 Hz, 1 H), 7.70–7.66 (m, 1 H), 7.60–
7.56 (m, 1 H), 7.11–7.07 (m, 1 H).
Eluent: Hexane/EtOAc (87:13); white solid; yield: 341 mg (91%); mp
227–229 °C.
1H NMR (500 MHz, CDCl3):  = 8.59 (d, J = 6.8 Hz, 1 H), 8.24–8.21 (m, 2
H), 7.75 (d, J = 8.9 Hz, 1 H), 7.54–7.46 (m, 3 H), 7.04–7.01 (m, 1 H).
13C NMR (125 MHz, CDCl3):  = 163.3, 151.7, 136.1, 129.7, 129.3,
13C NMR (125 MHz, CDCl3):  = 162.1, 151.8, 132.9, 132.7, 130.1,
129.0, 128.6, 128.3, 116.4, 113.8.
129.7, 128.5, 124.6, 122.3, 116.7, 114.3.
HRMS (ESI): m/z [M + H]+ calcd for C12H9ClN3: 230.0479; found:
HRMS (ESI): m/z [M + H]+ calcd for C12H9N4O2: 241.0720; found:
230.0477.
241.0716.
2-[4-(Trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyridine (5f)20
2-(2-Fluorophenyl)[1,2,4]triazolo[1,5-a]pyridine (5k)20
Eluent: Hexane/EtOAc (87:13); white solid; yield: 327 mg (90%); mp
234–236 °C.
Eluent: Hexane/EtOAc (85:15); white solid; yield: 297 mg (78%); mp
169–171 °C.
1H NMR (400 MHz, CDCl3):  = 8.61 (d, J = 6.8 Hz, 1 H), 8.41 (d, J = 8.0
Hz, 2 H), 7.80–7.74 (m, 3 H), 7.57–7.52 (m, 1 H), 7.07–7.03 (m, 1 H).
13C NMR (125 MHz, CDCl3):  = 162.8, 151.7, 134.2, 131.7 (q, J = 32.4
Hz), 129.8, 128.4, 127.5, 125.6 (d, J = 3.4 Hz), 124.1 (d, J = 272.1 Hz),
116.6, 114.1.
1H NMR (400 MHz, CDCl3):  = 8.68 (d, J = 6.8 Hz, 1 H), 8.28–8.24 (m, 1
H), 7.81 (d, J = 9.0 Hz, 1 H), 7.57–7.53 (m, 1 H), 7.49–7.43 (m, 1 H),
7.31–7.23 (m, 2 H), 7.07–7.03 (m, 1 H).
13C NMR (125 MHz, CDCl3):  = 161.8, 160.3 (d, J = 129.0 Hz), 151.1,
131.5 (d, J = 8.6 Hz), 130.9, 129.7, 128.5, 124.3, 118.8, 116.8, 116.6,
113.8.
HRMS (ESI): m/z [M + H]+ calcd for C13H9F3N3: 264.0743; found:
264.0738.
HRMS (ESI): m/z [M + H]+ calcd for C12H9FN3: 214.0775; found:
214.0776.
2-(m-Tolyl)[1,2,4]triazolo[1,5-a]pyridine (5g)20
2-(Thiophen-2-yl)[1,2,4]triazolo[1,5-a]pyridine (5l)20
Eluent: Hexane/EtOAc (84:16); white solid; yield: 382 mg (91%); mp
150–152 °C.
Eluent: Hexane/EtOAc (85:15); white solid; yield: 311 mg (80%); mp
168–170 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

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1H NMR (500 MHz, CDCl3):  = 8.57 (d, J = 6.8 Hz, 1 H), 7.89 (dd, J = 3.6,
1.2 Hz, 1 H), 7.73 (d, J = 8.9 Hz, 1 H), 7.53–7.49 (m, 1 H), 7.45 (dd, J =
5.0, 1.2 Hz, 1 H), 7.17 (dd, J = 5.0, 3.6 Hz, 1 H), 7.02–6.99 (m, 1 H).
1H NMR (400 MHz, CDCl3):  = 8.45 (d, J = 6.9 Hz, 1 H), 8.27 (dd, J = 8.0,
1.6 Hz, 2 H), 7.51–7.45 (m, 4 H), 6.80 (dd, J = 6.9, 1.6 Hz, 1 H), 2.47 (s, 3
H).
13C NMR (100 MHz, CDCl3):  = 160.2, 151.5, 133.6, 129.8, 128.2,
13C NMR (125 MHz, CDCl3):  = 164.2, 151.9, 141.0, 130.9, 129.9,
128.0, 127.9, 127.7, 116.2, 113.7.
128.6, 127.2, 116.1, 115.0, 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C10H8N3S: 202.0433; found:
HRMS (ESI): m/z [M + H]+ calcd for C13H12N3: 210.1025; found:
202.0436.
210.1028.
2-Cyclohexyl[1,2,4]triazolo[1,5-a]pyridine (5m)
7-Chloro-2-phenyl[1,2,4]triazolo[1,5-a]pyridine (5r)20
Eluent: Hexane/EtOAc (82:18); white solid; yield: 334 mg (86%); mp
96–98 °C.
Eluent: Hexane/EtOAc (84:16); white solid; yield: 391 mg (85%); mp
198–200 °C.
1H NMR (400 MHz, CDCl3):  = 8.52 (d, J = 6.8 Hz, 1 H), 7.67 (d, J = 8.9
Hz, 1 H), 7.47–7.43 (m, 1 H), 6.96–6.92 (m, 1 H), 3.00–2.92 (m, 1 H),
2.15–2.12 (m, 2 H), 1.89–1.85 (m, 2 H), 1.76–1.66 (m, 2 H), 1.50–1.26
(m, 4 H).
1H NMR (400 MHz, CDCl3):  = 8.50 (dd, J = 7.2, 0.7 Hz, 1 H), 8.27–8.24
(m, 2 H), 7.74 (dd, J = 2.2, 0.7 Hz, 1 H), 7.53–7.47 (m, 3 H), 6.99 (dd, J =
7.2, 2.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 165.3, 151.8, 136.2, 130.4, 130.3,
128.8, 128.4, 127.4, 115.5, 115.2.
13C NMR (100 MHz, CDCl3):  = 171.3, 150.9, 129.0, 128.0, 115.9,
112.9, 38.1, 31.9, 26.1, 25.9.
HRMS (ESI): m/z [M + H]+ calcd for C12H16N3: 202.1338; found:
HRMS (ESI): m/z [M + H]+ calcd for C12H9ClN3: 230.0479; found:
230.0481.
202.1336.
7-Methyl-2-(p-tolyl)[1,2,4]triazolo[1,5-a]pyridine (5s)
2-Cyclopropyl[1,2,4]triazolo[1,5-a]pyridine (5n)
Eluent: Hexane/EtOAc (84:16); white solid; yield: 377 mg (92%); mp
194–196 °C.
1H NMR (400 MHz, CDCl3):  = 8.41 (d, J = 6.9 Hz, 1 H), 8.15 (d, J = 8.1
Hz, 2 H), 7.47 (s, 1 H), 7.29 (d, J = 8.1 Hz, 2 H), 6.76 (d, J = 6.9 Hz, 1 H),
2.44 (s, 3 H), 2.41 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 164.2, 151.8, 140.8, 140.0, 129.4,
128.1, 127.2, 127.1, 115.9, 114.8, 21.5, 21.4.
Eluent: Hexane/EtOAc (82:18); pale yellow liquid; yield: 337 mg
(80%).
1H NMR (400 MHz, CDCl3):  = 8.46 (d, J = 6.8 Hz, 1 H), 7.59 (d, J = 8.9
Hz, 1 H), 7.45–7.41 (m, 1 H), 6.93–6.90 (m, 1 H), 2.25–2.19 (m, 1 H),
1.17–1.06 (m, 4 H).
13C NMR (125 MHz, CDCl3):  = 169.0, 151.1, 129.1, 127.7, 115.5,
112.7, 9.2, 8.8.
HRMS (ESI): m/z [M + H]+ calcd for C14H14N3: 224.1182; found:
224.1177.
HRMS (ESI): m/z [M + H]+ calcd for C9H10N3: 160.0869; found:
160.0866.
2-(4-Chlorophenyl)-7-methyl[1,2,4]triazolo[1,5-a]pyridine (5t)
2-Propyl[1,2,4]triazolo[1,5-a]pyridine (5o)
Eluent: Hexane/EtOAc (84:16); white solid; yield: 374 mg (94%); mp
202–204 °C.
1H NMR (400 MHz, CDCl3):  = 8.43 (d, J = 7.0 Hz, 1 H), 8.21–8.18 (m, 2
H), 7.48–7.43 (m, 3 H), 6.82 (dd, J = 7.0, 1.7 Hz, 1 H), 2.48 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 163.2, 151.9, 141.2, 135.9, 129.5,
128.9, 128.5, 127.2, 116.2, 114.9, 21.6.
Eluent: Hexane/EtOAc (82:18); pale yellow liquid; yield: 344 mg
(82%).
1H NMR (400 MHz, CDCl3):  = 8.54–8.52 (m, 1 H), 7.69–7.67 (m, 1 H),
7.47–7.44 (m, 1 H), 6.96–6.93 (m, 1 H), 2.93–2.90 (m, 2 H), 1.94–1.88
(m, 2 H), 1.06–1.02 (m, 3 H).
13C NMR (100 MHz, CDCl3):  = 167.3, 151.0, 129.2, 127.9, 115.8,
113.0, 30.6, 21.6, 13.8;
HRMS (ESI): m/z [M + H]+ calcd for C13H11ClN3: 244.0636; found:
244.0631.
HRMS (ESI): m/z [M + H]+ calcd for C9H12N3: 162.1025; found:
162.1023.
Funding Information
2-Isopropyl[1,2,4]triazolo[1,5-a]pyridine (5p)
The authors thank the SERB, New Delhi, India for financial support in
Eluent: Hexane/EtOAc (82:18); pale yellow liquid; yield: 340 mg
(81%).
the form of NPDF (PDF/2016/000177).
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1H NMR (500 MHz, CDCl3):  = 8.52 (d, J = 6.8 Hz, 1 H), 7.68 (d, J = 8.9
Hz, 1 H), 7.48–7.45 (m, 1 H), 6.96–6.93 (m, 1 H), 3.32–3.24 (m, 1 H),
1.45 (d, J = 7.0 Hz, 6 H).
Acknowledgment
13C NMR (100 MHz, CDCl3):  = 172.3, 151.1, 129.1, 128.1, 116.0,
113.0, 28.7, 21.7.
HRMS (ESI): m/z [M + H]+ calcd for C9H12N3: 162.1025; found:
The author T. N. thanks the CSIR, New Delhi for financial support in
the form of fellowship (CSIR-IICT Commun. No.
IICT/pubs./2018/324).
a
162.1027.
Supporting Information
7-Methyl-2-phenyl[1,2,4]triazolo[1,5-a]pyridine (5q)20
Supporting information for this article is available online at
Eluent: Hexane/EtOAc (84:16); white solid; yield: 387 mg (92%); mp
142–144 °C.
https://doi.org/10.1055/s-0037-1611854.
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References
Chem. Int. Ed. 2005, 44, 3656. (d) Moriarty, R. M. J. Org. Chem.
2005, 70, 2893. (e) Richardson, R. D.; Wirth, T. Angew. Chem. Int.
Ed. 2006, 45, 4402. (f) Zhdankin, V. V.; Stang, P. J. Chem. Rev.
2008, 108, 5299. (g) Dohi, T.; Kita, Y. Chem. Commun. 2009, 16,
2073. (h) Zhdankin, V. V. J. Org. Chem. 2011, 76, 1185.
(1) (a) Walsh, C. Tetrahedron Lett. 2015, 56, 3075. (b) Gomtsyan, A.
Chem. Heterocycl. Compd. 2012, 48, 7. (c) Chen, D.; Su, S.-J.; Cao,
Y. J. Mater. Chem. C 2014, 2, 9565.
(2) (a) Gurjar, A. S.; Andrisano, V.; Simone, A. D.; Velingkar, V. S.
Bioorg. Chem. 2014, 57, 90. (b) Perlovich, G. L.; Proshin, A. N.;
Volkova, T. V.; Petrova, L. N.; Bachurin, S. O. Mol. Pharm. 2012, 9,
2156. (c) Holla, B. S.; Veerendra, B.; Shivananda, M. K.; Poojary,
B. Eur. J. Med. Chem. 2003, 38, 759. (d) Xia, Y.; Qu, F.; Pang, L.
Mini-Rev. Med. Chem. 2010, 10, 806.
(3) (a) Leung-Toung, R.; Tam, T. F.; Zhao, Y.; Simpson, C. D.; Li, W.;
Desilets, D.; Karimian, K. J. Org. Chem. 2005, 70, 6230.
(b) Kumita, I.; Niwa, A. J. Pestic. Sci. 2001, 26, 60. (c) Varvaresou,
A.; Tsantili-Kakoulidou, A.; Siatra-Papastaikoudi, T.; Tiligada, E.
Arzneimittelforschung 2000, 50, 48. (d) Xu, J.; Cao, Y.; Zhang, J.;
Yu, S.; Zou, Y.; Chai, X.; Wu, Q.; Zhang, D.; Jiang, Y.; Sun, Q. Eur. J.
Med. Chem. 2011, 46, 3142.
(4) (a) Yamanaka, T.; Ohki, H.; Ohgaki, M.; Okuda, S.; Toda, A.;
Kawabata, K.; Inoue, S.; Misumi, K.; Itoh, K.; Satoh, K. Patent US
2005004094 A1, 2005. (b) Akerblom, E. B.; Campbell, D. E. S.
J. Med. Chem. 1973, 16, 312. (c) Ezabadi, I. R.; Camoutsis, C.;
Zoumpoulakis, P.; Geronikaki, A.; Sokovic, M.; Glamocilija, J.;
Ciric, A. Bioorg. Med. Chem. 2008, 16, 1150. (d) Gulerman, N. N.;
Dogan, H. N.; Rollas, S.; Johansson, C.; Celik, C. Farmaco 2001,
56, 953.
(5) (a) Unangst, P. C.; Shrum, G. P.; Connor, D. T.; Dyer, R. D.;
Schrier, D. J. J. Med. Chem. 1992, 35, 3691. (b) Maddila, S.; Gorle,
S.; Singh, M.; Lavanya, P.; Jonnalagadda, S. B. Lett. Drug Design.
Dis. 2013, 10, 977.
(6) Castro, A.; Castaño, T.; Encinas, A.; Porcal, W.; Gil, C. Bioorg.
Med. Chem. 2006, 14, 1644.
(7) Bo, Y.; Lin, C.; Ruiying, F.; Zhiping, G. Eur. J. Pharmacol. 1999,
380, 145.
(8) Roberts, J.; Schock, K.; Marino, S.; Andriole, V. T. Antimicrob.
Agents Chemother. 2000, 44, 3381.
(9) Santen, R. J. Steroids 2003, 68, 559.
(10) (a) Cashman, J.-R.; Hanzlik, R.-P. J. Org. Chem. 1982, 47, 4645.
(b) Shah, A. A.; Khan, Z. A.; Choudhary, N.; Loholter, C.; Schafer,
S.; Marie, G. P. L.; Faroog, U.; Witulski, B.; Wirth, T. Org. Lett.
2009, 11, 3578. (c) Ryu, I. A.; Park, J. Y.; Han, H. C.; Gong, Y.-D.
Synlett 2009, 999. (d) Mayhoub, A. S.; Kiselev, E.; Cushman, M.
Tetrahedron Lett. 2011, 52, 4941.
(11) (a) Meanwell, N. A.; Romine, J. L.; Rosenfeld, M. J.; Martin, S. W.;
Trehan, A. K.; Wright, J. J. K.; Malley, M. F.; Gougoutas, J. Z.;
Brassard, C. L.; Buchanan, J. O.; Federic, M. E.; Fleming, J. S.;
Gamberdella, M.; Hartl, K. S.; Zavoico, G. B.; Seiler, S. M. J. Med.
Chem. 1993, 36, 3884. (b) Reichelt, A.; Falsey, J. R.; Rzasa, R. M.;
Thiel, O. R.; Achmatowicz, M. M.; Larsen, R. D.; Zhang, D. Org.
Lett. 2010, 12, 792.
(13) For examples of C–C bond forming heterocycles using hyperva-
lent iodine(III) reagents, see: (a) Yu, W.; Du, Y.; Zhao, K. Org.
Lett. 2009, 11, 2417. (b) Depken, C.; Kratzschmar, F.; Breder, A.
Org. Chem. Front. 2016, 3, 314. (c) Matcha, K.; Narayan, R.;
Antonchick, A. P. Angew. Chem. Int. Ed. 2013, 52, 7985. (d) Liu, L.;
Lu, H.; Wang, H.; Yang, C.; Zhang, X.; Zhang-Negrerie, D.; Du, Y.;
Zhao, K. Org. Lett. 2013, 15, 2906. (e) Lv, J.; Zhang-Negrerie, D.;
Deng, J.; Du, Y.; Zhao, K. J. Org. Chem. 2014, 79, 1111.
(14) For examples of C–X (X = N, O, S) bond forming heterocycles
using hypervalent iodine(III) reagents, see: (a) Farid, U.; Wirth,
T. Angew. Chem. Int. Ed. 2012, 51, 3462. (b) Kim, H. J.; Cho, S. H.;
Chang, S. Org. Lett. 2012, 14, 1424. (c) Sun, J.; Zhang-Negrerie,
D.; Du, Y.; Zhao, K. J. Org. Chem. 2015, 80, 1200. (d) Lu, S.-C.;
Zheng, P.-R.; Liu, G. J. Org. Chem. 2012, 77, 7711. (e) Li, J.; Chen,
H.; Zhang-Negrerie, D.; Du, Y.; Zhao, K. RSC Adv. 2013, 3, 4311.
(f) Zheng, Y.; Li, X.; Ren, C.; Zhang-Negrerie, D.; Du, Y.; Zhao, K.
J. Org. Chem. 2012, 77, 10353. (g) Downer-Riley, N. K.; Jackson,
Y. A. Tetrahedron 2008, 64, 7741. (h) Kumar, A.; Maurya, R. A.;
Ahmad, P. J. Comb. Chem. 2009, 11, 198.
(15) For examples of N–X (X = N, O, S) bond forming heterocycles
using hypervalent iodine(III) reagents, see: (a) Wang, K.; Fu, X.;
Liu, J.; Liang, Y.; Dong, D. Org. Lett. 2009, 11, 1015. (b) Correa, A.;
Tellitu, I.; Domínguez, E.; SanMartin, R. Tetrahedron 2006, 62,
11100. (c) Prakash, O.; Saini, R. K.; Singh, S. P.; Varma, R. S. Tet-
rahedron Lett. 1997, 38, 3147. (d) Correa, A.; Tellitu, I.;
Domínguez, E.; SanMartin, R. Org. Lett. 2006, 8, 4811. (e) Anand,
D.; Patel, O. P. S.; Maurya, R. K.; Kant, R.; Yadav, P. P. J. Org. Chem.
2015, 80, 12410.
(16) (a) Ryu, T.; Min, J.; Choi, W.; Jeon, W. H.; Lee, P. H. Org. Lett.
2014, 16, 2810. (b) Mariappan, A.; Rajaguru, K.; Chola, N. M.;
Muthusubramanian, S.; Bhuvanesh, N. J. Org. Chem. 2016, 81,
6573. (c) Tumula, N.; Palakodety, R. K.; Balasubramanian, S.;
Nakka, M. Adv. Synth. Catal. 2018, 360, 2806.
(17) (a) Tumula, N.; Jatangi, N.; Palakodety, R. K.; Balasubramanian,
S.; Nakka, M. J. Org. Chem. 2017, 82, 5310. (b) Jatangi, N.;
Tumula, N.; Palakodety, R. K.; Nakka, M. J. Org. Chem. 2018, 83,
5715. (c) Nakka, M.; Tadikonda, R.; Nakka, S.; Vidavalur, S. Adv.
Synth. Catal. 2016, 358, 520. (d) Nakka, M.; Tadikonda, R.;
Rayavarapu, S.; Sarakula, P.; Vidavalur, S. Synthesis 2015, 47,
517.
(18) Yadav, V. K.; Babu, K. G. Eur. J. Org. Chem. 2005, 452.
(19) Mamaeva, E. A.; Bakibaev, A. A. Tetrahedron 2003, 59, 7521.
(20) (a) Song, L.; Tian, X.; Lv, Z.; Li, E.; Wu, J.; Liu, Y.; Yu, W.; Chang, J.
J. Org. Chem. 2015, 80, 7219. (b) Zheng, Z.; Ma, S.; Tang, L.;
Zhang-Negrerie, D.; Du, Y.; Zhao, K. J. Org. Chem. 2014, 79, 4687.
(c) Ueda, S.; Nagasawa, H. J. Am. Chem. Soc. 2009, 131, 15080.
(d) Meng, X.; Yu, C.; Zhao, P. RSC Adv. 2014, 4, 8612.
(12) For selected reviews on hypervalent iodine reagents, see:
(a) Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328.
(b) Stang, P. J. J. Org. Chem. 2003, 68, 2997. (c) Wirth, T. Angew.
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