Straightforward and Expeditious One-Pot Tandem Synthesis of 3,5-Diaryl-1,2,4-Selenadiazoles from Aryl Nitriles

Article abstract of DOI:10.1055/s-0039-1690126

A one-pot process for the efficient synthesis of 3,5-diaryl-1,2,4-selenadiazoles from aryl nitriles has been developed. This tandem transformation was performed in excellent yields (91-98percent) via in situ selenoamidation and a subsequent oxidative dime

Full text of DOI:10.1055/s-0039-1690126

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–E
paper
A
en
S. Majnooni et al.
Paper
Synthesis
Straightforward and Expeditious One-Pot Tandem Synthesis of
3,5-Diaryl-1,2,4-Selenadiazoles from Aryl Nitriles
Sahar Majnoonia
Zainab Almansafb
Miu Tsujib
Ahmad R. Khosropour*a,b
Hassan Zali-Boeini*a
M. Hassan Beyzavi*b
1. Se, NaBH4, Py, HCl,
Ar
Se
N
DMSO, 80 °C
2 Ar
C N
N
2. TCT, 25 °C
Ar
12 examples, 91–98%
Fast and Low-Cost
Safe and Efficient
a Department of Chemistry, University of Isfahan, Isfahan,
81746-73441, Iran
khosropour@chem.ui.ac.ir
hzaliboeini@gmail.com
b Department of Chemistry and Biochemistry, University of
Arkansas, Fayetteville, Arkansas 72701, USA
akhosrop@uark.edu
beyzavi@uark.edu
Received: 22.05.2019
Accepted after revision: 25.06.2019
Published online: 08.08.2019
Despite the extensive biological activities and synthetic
applications of 1,2,4-selenadiazoles, the practical proce-
dures for the synthesis of these compounds is still limited.
The most common routes for the synthesis of 3,5-disubsti-
tuted 1,2,4-selenadiazoles are concentrated on the di-
merization of primary selenoamides through the utilization
DOI: 10.1055/s-0039-1690126; Art ID: ss-2019-m0286-op
Abstract A one-pot process for the efficient synthesis of 3,5-diaryl-
1,2,4-selenadiazoles from aryl nitriles has been developed. This tandem
transformation was performed in excellent yields (91–98%) via in situ
selenoamidation and a subsequent oxidative dimerization reaction. This
method features relatively mild reaction conditions, operational sim-
plicity, straightforward separation of the products, and the utilization of
inexpensive reagents.
13
of iodine,11 NBS,12 PhI(OAc)2 and Oxone (Scheme 1, A).14
These compounds can also be prepared through palladi-
um(II) salts15 or by utilizing α-bromo ketones (Scheme 1, B
and C).16
Key words selenadiazoles, selenoamides, cyanuric chloride, dimethyl
sulfoxide, oxidative dimerization
Previous work
Se
Se
Ar
N
Oxidants
A)
N
Ar
NH2
During the last few decades, interest in organoselenium
motifs has increased due to their broad applications in
many areas, such as semiconductor preparation,1 biochem-
istry investigations,2 catalyst synthesis3 and, particularly,
their beneficial effects in human health, which makes these
compounds robust in biological and medicinal chemistry.2,4
Among them, selenadiazole scaffolds are a significant class
of five-membered heterocyclic compounds, containing se-
lenium and nitrogen heteroatoms, which have revealed
unique properties, such as antibacterial,5 anti-HIV,6 antimi-
crobial,7 anticancer,8 antifungal9 and antitumor10 activities
(Figure 1).
Ar
Oxidants: I2, NBS, PhI(OAc)2, Oxone
3–100%
Se
Se
Ar
N
Na2PdCl4
B)
C)
N
Ar
NH2
Ar
12–78%
O
Se
O
Se
R
Ar
N
S
0 °C
Ar
NH2
+
Ph
N
O
Br
Ar
44–47%
This work
Se
N
Ar
1) Se, NaBH4, Py, HCl
DMSO, 80 °C
N
D)
2 Ar CN
2) TCT, r.t.
Ar
91–98%
O
Scheme 1 Synthetic routes to 1,2,4-selenadiazoles
Se
Se
N
O
N
N
N
NH
S
N
Nonetheless, various limitations are associated with
these protocols, such as harsh manipulations, the use of
metal catalysts, low yields and prolonged reaction times.11–16
However, the major drawback of these methods is the effort
required for the synthesis of selenoamides as key substrate
in a separate step. Usually selenoamides are prepared using
highly toxic and unstable reagents, such as H2Se or NaSeH
Fe
Fe
Se
N
O
Cl
Antitumor agent
Antibacterial agent
Anti-HIV agent
Cl
Figure 1 Representative bioactive selenadiazoles
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
S. Majnooni et al.
Paper
Synthesis
(generated from NaBH4/Se,17 LiAlHSeH18), Se/CO,19
tris(trimethylsilyl) monoselenophosphate,20 P2Se5/H2O,21
Al2Se3 in the presence of Et3N/pyridine/H2O2,22 and
P2Se5/EtOH/H2O.21a Considering the risks in using these re-
agents and the purification problems, developing a novel
one-pot tandem strategy in order to minimize the purifica-
tion process and increase chemical efficiency is highly de-
manded.
Due to the ease of nucleophilic substitution reactions of
cyanuric chloride (TCT), it has emerged as a fascinating re-
agent in various synthetic transformations with broad ap-
plication in organic synthesis.23 However, to the best of our
knowledge, TCT has not been utilized for the formation of
an N–Se bond so far.
In continuation of our efforts to develop new and practi-
cal methods for the synthesis of heterocycles,24 we herein
present the first one-pot tandem procedure for the prepa-
ration of symmetrical 3,5-diaryl-1,2,4-selenadiazoles. In
this protocol, aryl nitrile is applied directly as the starting
material in dimethyl sulfoxide (DMSO) for the access to the
desired products by a one-pot two-step sequential reaction
(Scheme 1, D).
At the outset, the optimal reaction conditions were de-
vised utilizing benzonitrile (1a) for the synthesis of 3,5-di-
phenyl-1,2,4-selenadiazole (2a) as a template reaction. We
investigated the effects of solvent, temperature and the
amount of TCT, as shown in Table 1.
At first, the reaction of benzonitrile (1a) with Se/NaBH4
was carried out in EtOH under N2 atmosphere in the pres-
ence of pyridine and dilute hydrochloric acid for 150 min-
utes. A mixture of TCT in DMSO was subsequently added to
the reaction medium and the mixture was stirred at room
temperature for about 10 minutes, affording the corre-
sponding 1,2,4-selenadiazole 2a in 85% yield (Table 1, entry
1). According to numerous literature reports of the suitable
activity of NaBH4 in DMSO,25 we performed a practical
modification of this method by replacing EtOH by DMSO
which performs the dual function of solvent and reagent
along with TCT. It was found that the efficiency of the reac-
tion was improved significantly and the best yield (96%)
was obtained (entry 5). Therefore, DMSO was chosen as the
optimal solvent. The employment of other solvents was not
satisfactory in this reaction (entries 2–4). Next, we investi-
gated the effect of temperature on the reaction progress
and found that the best yield was obtained when the con-
version of benzonitrile into the corresponding benzosele-
namide was performed at 80 °C, with subsequent TCT addi-
tion at ambient temperature. Increasing the temperature
did not effect improvement of the yield (entries 6 and 8).
On the other hand, the TCT amount was also evaluated un-
der the reaction conditions (entries 5, 9 and 10). As illus-
trated in Table 1, 0.34 mmol of TCT was sufficient to give an
excellent yield of the desired product (entry 5).
Under the optimized conditions, the substrate scope
and limitations of this protocol were examined utilizing di-
verse aromatic and aliphatic nitriles (Scheme 2). The results
revealed that aromatic nitriles bearing an electron-donating
group, such as methyl (2b and 2c) and methoxy (2d), as
well as ones with an electron-withdrawing group [e.g., Cl
(2e–g), Br (2h and 2i), CN (2j and 2k), CF3 (2l)] are compati-
ble with this method and the desired products were ob-
tained in excellent yields (91–98%). It is noteworthy to
mention that nitriles possessing a group at the ortho-posi-
tion provided the products in slightly lower yields (91–92%)
due to steric hindrance (entries 2c and 2g). Furthermore,
efforts to extend this methodology to aliphatic nitriles were
not successful and an unidentified mixture was obtained.
Inspired by our experimental results and previous re-
ports,24 a possible mechanism for this transformation is de-
picted in Scheme 3. Initially, benzoselenoamide (3a) is easi-
ly prepared by the reaction of benzonitrile (1a) with seleni-
um powder and NaBH4 in DMSO in the presence of pyridine
and dilute hydrochloric acid. Meanwhile, chlorodimethyl-
sulfonium ion (4) as an active intermediate is prepared via
the reaction of TCT and DMSO. Subsequently, Se–Cl bond
formation of benzoselenoamide in the presence of the reac-
tive intermediate leads to the formation of 5 which, after a
dimerization reaction with another benzoselenoamide,
provides N-substituted benzoselenoamide 6. Eventually, in-
tramolecular cyclization of 6 and then aromatization via re-
lease of H2Se affords the corresponding 3,5-diphenyl-1,2,4-
selenadiazole (2a).
Table 1 Optimization of the Reaction Conditions for the Synthesis of
2aa
Ph
1) Se, NaBH4, Py, HCl
Solvent, Temp (T1)
Se
N
CN
N
2) TCT, DMSO, Temp (T2)
Ph
2a
1a
Entry
Solvent
Molar ratio
(TCT/DMSO; step 2)
Temp (°C)
Yield
(%)b
T1
T2
r.t.
1
2
EtOH
0.34:1
0.34:1
0.34:1
0.34:1
0.34:0
0.34:0
0.34:0
0.34:0
0.2:0
80
80
80
80
80
85
64
MeOH
toluene
CH3CN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
80
3
trace
4
trace
96
5
6
100
60
80
80
80
96
7
83
8
96
9
r.t.
r.t.
65
10
0.4:0
96
a Reaction conditions: (1) Se (8 mmol), NaBH4 (8.8 mmol), solvent (4 mL),
N2 atmosphere, 20 min; then, addition of 1a (2 mmol), pyridine (1.29 mL,
16 mmol), HCl (2 N, 4 mL), 2 h; (2) TCT/DMSO, r.t., 10 min.
b Isolated yields.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

C
S. Majnooni et al.
Paper
Synthesis
Ar
Se
N
1. Se, NaBH4, Py, HCl
DMSO, 80 °C
2
Ar
C N
N
2
2. TCT, 25 °C
1
Ar
H3CO
Cl
Se
N
Se
N
Se
N
Cl
Se
N
Se
N
Se
N
N
N
N
N
N
N
Cl
OCH3
Cl
2a, 96%
(T1:150 min, T2: 10 min)
2b, 97%
(T1: 150 min, T2: 7 min)
2c, 92%
(T1: 150 min, T2: 15 min)
2d, 98%
(T1: 150 min, T2: 7 min)
2e, 96%
2f, 95%
(T1: 140 min, T2: 15 min) (T1: 140 min, T2: 15 min)
F3C
Br
NC
Se
N
Se
N
N
Se
N
N
Br
NC
Se
N
Se
N
N
Se
N
N
Cl
N
N
Cl
Br
CN
CF3
Br
CN
2g, 91%
(T1: 150 min, T2: 15 min)
2h, 96%
(T1: 140 min, T2: 15 min)
2i, 95%
(T1: 140 min, T2: 15 min)
2j, 94%
(T1: 120 min, T2: 15 min)
2k, 93%
2l, 92%
(T1: 120 min, T2: 15 min) (T1: 130 min, T2: 15 min)
Scheme 2 Substrate scope of the reaction
Se
CN
Se, NaBH4, DMSO
Pyridine, HCl
NH2
3a
1a
S
N
Cl
N
O
N
O
O
S
Cl
Cl
N
N
N
N
N
+
S
Cl
Cl
Cl
Cl
Cl
N
Cl
4
Cl
Se
NH2
Se
Cl
S
4
S
NH
+
3a
5
Cl
Se
NH2
Se
Se
N
Se HN
N
+
HN
– H2Se
HN Se
2a
3a
5
6
Scheme 3 Plausible route
In summary, we have developed a novel tandem one-
pot multistep protocol for the efficient conversion of ben-
zonitrile derivatives into the corresponding 1,2,4-selenadi-
azoles. The main feature of this transformation is the in situ
formation of selenoamide/oxidative dimerization reaction,
reducing the number of purification processes, in excellent
yields.
All chemical reagents and solvents used in this work were obtained
from Merck and Sigma-Aldrich. The progress of reactions was moni-
tored by TLC (silica gel 60 F254). Melting points were determined
with a Stuart Scientific SMP-2 apparatus. 1H and 13C NMR spectra
were recorded on a Bruker Avance 400 MHz Fourier transform spec-
trometer. Coupling constants are reported in hertz (Hz). Fourier
transform infrared (FTIR) spectra were recorded on a Nicolet Impact
400D spectrophotometer (KBr pellets) in the range of 400–4000 cm–1
.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

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S. Majnooni et al.
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Synthesis
3,5-Disubstituted 1,2,4-Selenadiazoles 2a–l; General Procedure
1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 8.8 Hz, 2 H), 7.84 (d, J = 8.4
Hz, 2 H), 7.41–7.36 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 192.69, 173.38, 138.39, 136.29,
132.65, 132.46, 130.12, 129.68, 129.40, 128.96.
To a solution of selenium powder (8 mmol) in DMSO (4 mL) was add-
ed NaBH4 (8.8 mmol) under nitrogen atmosphere. The reaction mix-
ture was stirred at room temperature for about 20 min and then the
aryl nitrile 1 (2 mmol) and pyridine (1.29 mL, 16 mmol) were added.
Subsequently, the mixture was heated at 80 °C, while HCl (2 N, 4 mL)
was added dropwise over 30 min, and then stirring was continued.
The progress of the reaction was monitored by TLC. When the reac-
tion was completed, it was cooled to ambient temperature and TCT
(0.34 mmol) was added; the mixture was stirred at room tempera-
ture. After completion of the reaction, as monitored by TLC (petro-
leum ether/ethyl acetate, 8:2), the mixture was washed with water
(4.0 mL) and extracted with chloroform (2 × 5 mL). The extract was
dried over anhydrous Na2SO4, the solvent was removed under vacu-
um, MeOH/water (1:1, 5 mL) was added, and the solid phase was col-
lected by filtration and dried under vacuum to give the pure product.
3,5-Bis(3-chlorophenyl)-1,2,4-selenadiazole (2f)
Yield: 0.336 g (95%); white crystals; mp 123–125 °C.
IR (KBr): 3070, 2921, 1568, 1504, 1467, 1422, 1292, 1227, 1073, 979,
893, 786, 723 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.42 (s, 1 H), 8.29 (d, J = 7.6 Hz, 1 H),
8.05 (s, 1 H), 7.86 (d, J = 7.6 Hz, 1 H), 7.56 (d, J = 8 Hz, 1 H), 7.50–7.43
(m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 192.68, 173.06, 135.68, 135.54,
135.44, 134.75, 132.13, 130.68, 130.26, 130.02, 128.97, 127.76,
126.85, 126.65.
Anal. Calcd for C14H8Cl2N2Se: C, 47.49; H, 2.28; N, 7.91. Found: C,
47.63; H, 2.34; N, 7.84.
3,5-Diphenyl-1,2,4-selenadiazole (2a)
Yield: 0.274 g (96%); white crystals; mp 85–87 °C (Lit.13 85 °C).
IR (KBr): 3099, 3049, 2955, 2925, 2857, 1631, 1587, 1514, 1482, 1443,
3,5-Bis(2-chlorophenyl)-1,2,4-selenadiazole (2g)
1319, 1277, 1091, 963, 757, 679 cm–1
.
Yield: 0.322 g (91%); white crystals; mp 87–89 °C.
1H NMR (400 MHz, CDCl3): δ = 8.34–8.32 (m, 2 H), 7.95–7.92 (m, 2 H),
7.49–7.41 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 193.88, 174.46, 134.39, 134.15,
132.14, 130.11, 129.37, 128.81, 128.70, 128.26.
IR (KBr): 3057, 2951, 2918, 2849, 1588, 1490, 1448, 1308, 1267, 1109,
1051, 960, 781, 751 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.73–8.71 (m, 1 H), 8.01–7.99 (m, 1 H),
7.65–7.63 (m, 1 H), 7.56–7.54 (m, 1 H), 7.52–7.49 (m, 2 H), 7.43–7.41
(m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 183.67, 173.19, 133.62, 133.32,
132.39, 132.24, 131.36, 130.75, 130.54, 130.36, 129.93, 128.78,
127.64, 126.77.
3,5-Bis(4-methylphenyl)-1,2,4-selenadiazole (2b)
Yield: 0.304 g (97%); white crystals; mp 113–115 °C (Lit.13 122 °C).
IR (KBr): 3011, 2915, 2855, 1606, 1522, 1486, 1402, 1315, 1268, 1091,
1019, 961, 815 cm–1
.
Anal. Calcd for C14H8Cl2N2Se: C, 47.49; H, 2.28; N, 7.91. Found: C,
47.36; H, 2.36; N, 7.80.
1H NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 8.4 Hz, 2 H), 7.91 (d, J = 8.4
Hz, 2 H), 7.33–7.30 (dd, J = 8.4, 2.4 Hz, 4 H), 2.44 (s, 6 H).
3,5-Bis(4-bromophenyl)-1,2,4-selenadiazole (2h)
Yield: 0.425 g (96%); white crystals; mp 161–163 °C (Lit.13 162 °C).
3,5-Bis(2-methylphenyl)-1,2,4-selenadiazole (2c)
Yield: 0.288 g (92%); white crystals; mp 55–57 °C.
IR (KBr): 3043, 2919, 2860, 1583, 1506, 1471, 1392, 1309, 1282, 1231,
IR (KBr): 3047, 2923, 1591, 1518, 1475, 1440, 1415, 1366, 1328, 1274,
1068, 830 cm–1
.
1068, 759, 680 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.18 (d, J = 8.4 Hz, 2 H), 7.79 (d, J = 8.4
Hz, 2 H), 7.59–7.54 (m, 4 H).
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8 Hz, 1 H), 7.97 (d, J = 8 Hz,
1 H), 7.31–7.22 (m, 6 H), 2.60 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 192.87, 173.50, 133.06, 132.86,
132.66, 131.92, 130.36, 129.55, 126.86, 124.77.
13C NMR (100 MHz, CDCl3): δ = 188.13, 173.83, 138.10, 137.25,
132.45, 131.84, 131.25, 131.04, 130.93, 130.01, 129.87, 129.66,
129.37, 126.02, 22.88, 22.14.
3,5-Bis(3-bromophenyl)-1,2,4-selenadiazole (2i)
Anal. Calcd for C16H14N2Se: C, 61.35; H, 4.50; N, 8.94. Found: C, 61.22;
H, 4.63; N, 8.85.
Yield: 0.421 g (95%); white crystals; mp 133–135 °C.
IR (KBr): 3065, 2921, 2860, 1563, 1500, 1466, 1416, 1293, 1228, 1068,
977, 790, 725, 678 cm–1
.
3,5-Bis(4-methoxyphenyl)-1,2,4-selenadiazole (2d)
Yield: 0.338 g (98%); white crystals; mp 133–135 °C (Lit.13 137 °C).
1H NMR (400 MHz, CDCl3): δ = 8.57 (t, J = 2 Hz, 1 H), 8.35–8.33 (dt,
J = 7.6, 1.2 Hz, 1 H), 8.20 (t, J = 2 Hz, 1 H), 7.92–7.89 (dt, J = 8, 1.2 Hz, 1
H), 7.73–7.70 (m, 1 H), 7.64–7.61 (m, 1 H), 7.43–7.37 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 192.57, 172.91, 135.90, 135.64,
135.06, 133.18, 131.86, 130.90, 130.63, 130.28, 127.31, 127.10,
123.51, 122.86.
IR (KBr): 3056, 3004, 2936, 2833, 1605, 1581, 1487, 1414, 1305, 1275,
1247, 1166, 1089, 1030, 834 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 8.8 Hz, 2 H), 7.96 (d, J = 8.8
Hz, 2 H), 7.01 (d, J = 8.8 Hz, 4 H), 3.92 (s, 3 H), 3.90 (s, 3 H).
Anal. Calcd for C14H8Br2N2Se: C, 37.96; H, 1.82; N, 6.32. Found: C,
37.83; H, 1.90; N, 6.25.
3,5-Bis(4-chlorophenyl)-1,2,4-selenadiazole (2e)
Yield: 0.340 g (96%); white crystals; mp 159–161 °C (Lit.13 167 °C).
4,4′-(1,2,4-Selenadiazole-3,5-diyl)dibenzonitrile (2j)
IR (KBr): 3047, 2921, 1588, 1509, 1473, 1396, 1310, 1281, 1230, 1090,
1012, 965, 832, 732 cm–1
.
Yield: 0.315 g (94%); white crystals; mp 194–196 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

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S. Majnooni et al.
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Synthesis
IR (KBr): 3066, 2956, 2923, 2857, 2227, 1730, 1605, 1478, 1402, 1317,
1185, 1081, 967, 841 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.44 (d, J = 8.4 Hz, 2 H), 8.05 (d, J = 8.4
Hz, 2 H), 7.78–7.72 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 192.97, 172.10, 137.50, 137.21,
References
.
(1) Kanatzidis, M. G.; Huang, S. Coord. Chem. Rev. 1994, 130, 509.
(2) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004, 104,
6255.
(3) Braga, A. L.; Lüdtke, D. S.; Vargas, F.; Braga, R. C. Synlett 2006,
1453.
133.27, 132.67, 129.34, 128.69, 124.49, 118.62, 117.93, 113.76.
(4) Mugesh, G.; du Mont, W. W.; Sies, H. Chem. Rev. 2001, 101, 2125.
(5) (a) Karnik, A. V.; Kulkarni, A. M.; Malviya, N. J.; Mourya, B. R.;
Jadhav, B. L. Eur. J. Med. Chem. 2008, 43, 2615. (b) Al-Rubaie, A.
Z.; Al-Jadaan, S. A.; Muslim, S. K.; Saeed, E. A.; Ali, E. T.; Al-
Hasani, A. K.; Al-Salman, H. N.; Al-Fadal, S. A. J. Organomet.
Chem. 2014, 774, 43.
Anal. Calcd for C16H8N4Se: C, 57.33; H, 2.41; N, 16.71. Found: C, 57.45;
H, 2.49; N, 16.62.
3,3′-(1,2,4-Selenadiazole-3,5-diyl)dibenzonitrile (2k)
Yield: 0.312 g (93%); white crystals; mp 179–181 °C.
IR (KBr): 3071, 2955, 2921, 2855, 2227, 1581, 1496, 1476, 1405, 1320,
(6) Zhan, P.; Liu, X.; Fang, Z.; Pannecouque, C.; De Clercq, E. Bioorg.
Med. Chem. 2009, 17, 6374.
1167, 1085, 997, 801 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.64 (t, J = 2 Hz, 1 H), 8.57–8.54 (dt,
J = 8, 1.6 Hz, 1 H), 8.26 (t, J = 1.6 Hz, 1 H), 8.15–8.13 (dt, J = 8, 1.6 Hz, 1
H), 7.81–7.78 (dt, J = 7.6, 1.2 Hz, 1 H), 7.71–7.69 (dt, J = 7.6, 1.6 Hz, 1
H), 7.63–7.54 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 192.26, 172.32, 135.24, 134.89,
134.86, 133.52, 132.79, 132.59, 132.26, 131.37, 130.49, 129.72,
118.43, 117.54, 114.12, 113.17.
(7) Jadhav, A. A.; Dhanwe, V. P.; Joshi, P. G.; Khanna, P. K. Cogent
Chem. 2016, 2, 1144670.
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Chem. 2014, 84, 335. (b) Chen, T.; Zheng, W.; Wong, Y. S.; Yang,
F. Biomed. Pharmacother. 2008, 62, 77.
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Shafiee, A. Farmaco 2003, 58, 63.
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2009, 180, 54. (b) Mhaidat, N. M.; Al-Smadi, M.; Al-Momani, F.;
Alzoubi, K. H.; Mansi, I.; Al-Balas, Q. Drug Des., Dev. Ther. 2015,
9, 3645.
Anal. Calcd for C16H8N4Se: C, 57.33; H, 2.41; N, 16.71. Found: C, 57.20;
H, 2.49; N, 16.80.
3,5-Bis(4-(trifluoromethyl)phenyl)-1,2,4-selenadiazole (2l)
Yield: 0.388 g (92%); white crystals; mp 134–136 °C.
(11) Cohen, V. I. Synthesis 1978, 768.
(12) Shimada, K.; Matsuda, Y.; Hikage, S.; Takeishi, Y.; Takikawa, Y.
Bull. Chem. Soc. Jpn. 1991, 64, 1037.
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Zhdankin, V. V. Eur. J. Org. Chem. 2014, 5149.
(15) Al-Rubaie, A. Z.; Yousif, L. Z.; Al-Hamad, A. J. H. J. Organomet.
Chem. 2002, 656, 274.
IR (KBr): 2930, 1617, 1521, 1491, 1408, 1323, 1240, 1162, 1112, 1062,
1017, 836 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.43 (d, J = 8 Hz, 2 H), 8.04 (d, J = 8 Hz,
2 H), 7.72–7.67 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 192.90, 173.27, 137.03, 136.82, 133.75
(q, J = 33 Hz), 131.91 (q, J = 32 Hz), 129.12, 128.53, 126.49 (q, J = 4 Hz),
125.75 (q, J = 4 Hz), 124.95, 122.67.
(16) Shafiee, A.; Ebrahimzadeh, M. A.; Maleki, A. J. Heterocycl. Chem.
1999, 36, 901.
(17) Klayman, D. L.; Griffin, T. S. J. Am. Chem. Soc. 1973, 95, 197.
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2001, 123, 8408.
Anal. Calcd for C16H8F6N2Se: C, 45.62; H, 1.91; N, 6.65. Found: C,
45.48; H, 1.99; N, 6.73.
(19) Ogawa, A.; Miyaka, J.; Karasaki, Y.; Murai, S.; Sonoda, N. J. Org.
Chem. 1985, 50, 384.
Funding Information
(20) Kamiñski, R.; Glass, R. S.; Skowroñska, A. Synthesis 2001, 1308.
(21) (a) Geisler, K.; Jacobs, A.; Künzler, A.; Mathes, M.; Girrleit, H.;
Zimmermann, B.; Bulka, E.; Pfeiffer, W.-D.; Langer, P. Synlett
2002, 1983. (b) Geisler, K.; Pfeiffer, W.-D.; Künzler, A.; Below, H.;
Bulka, E.; Langer, P. Synthesis 2004, 875.
(22) Cohen, V. I. Synthesis 1978, 668.
(23) (a) Iranpoor, N.; Panahi, F. Org. Lett. 2015, 17, 214. (b) Kangani,
C. O.; Day, B. W. Org. Lett. 2008, 10, 2645.
M.H.B. gratefully acknowledges financial support through the startup
funds from the University of Arkansas. A.R.K. and H.Z.B. gratefully
thank the Center of Excellence of Chemistry and the Research Council
of the University of Isfahan (CECUI) for financial support of this work.
The authors declare no competing financial interest.()
(24) (a) Khosropour, A. R.; Noei, J. Monatsh. Chem. 2010, 141, 649.
(b) Zali-Boeini, H.; Mansouri, S. G. Synth. Commun. 2015, 45,
1681.
Supporting Information
Supporting information for this article is available online at
(25) (a) Barros, M. T.; Maycock, C. D.; Ventura, M. R. Tetrahedron Lett.
1999, 40, 557. (b) Zheng, Y.; Xiong, C.; Wang, Z.; Zhang, L.
J. Bioact. Compat. Polym. 2015, 30, 302. (c) Hutchins, R. O.;
Lamson, D. W.; Rua, L.; Milewski, C.; Maryanoff, B. J. Org. Chem.
1971, 36, 803.
https://doi.org/10.1055/s-0039-1690126.
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E