One-pot synthesis of 5-arylamino-1,3,4-selenadiazol-2(3H)-ones from arylisoselenocyanates

Article abstract of DOI:10.3184/174751912X13377840596361

A one-pot reaction of arylisoselenocyanates, hydrazine and bis(trichloromethyl) carbonate, in the presence of a base provides an efficient route for the synthesis of 5-arylamino-1,3,4-selenadiazol-2(3H)-ones in good to excellent yields. A plausible mechan

Full text of DOI:10.3184/174751912X13377840596361

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 421
JULY, 421–424
One-pot synthesis of 5-arylamino-1,3,4-selenadiazol-2(3H)-ones from
arylisoselenocyanates
Yuanyuan Xie*, Ping Yang and Xiaodong Chen
Key Laboratory for Green PharmaceuticalTechnologies and Related Equipment of Ministry of Education, College of Pharmaceutical
Sciences, Zhejiang University ofTechnology, Hangzhou 310014, P. R. China
A one-pot reaction of arylisoselenocyanates, hydrazine and bis(trichloromethyl) carbonate, in the presence of a base
provides an efficient route for the synthesis of 5-arylamino-1,3,4-selenadiazol-2(3H)-ones in good to excellent yields.
A plausible mechanism is proposed for the reaction.
Keywords: arylisoselenocyanates, selenadiazole, bis(trichloromethyl) carbonate, cyclisation, tandem reaction
Selenium, a recognised dietary antioxidant, is now known to
be an essential component of the active sites of several
enzymes, including glutathione peroxidase (GSH-Px)1−2 and
thioredoxin reductase.3 The interest in the chemistry of organo-
selenium compounds has increased in a few decades due to
their synthetic applications4−5 and biological activities.6−7 It
has been reported that selenium-containing heterocycles
show anti-cancer,8−11 anti-inflammatory,12−13 antibacterial,14−15
antileishmanial16 and antioxidant properties.17−19
Useful key starting materials for preparation of selenium-
containing heterocycles include selenoamides, selenoureas,
selenazadienes, and isoselenocyanates. Among all these
reagents, aryl and alkyl isoselenocyanates have emerged as
powerful tools for the synthesis of selenium-containing hetero-
cycles because of their convenient preparation, low toxicity,
relative stability, and excellent reactivity.20–27
Isoselenocyanatobenzene 1a was selected as the substrate to
optimise the reaction conditions. When isoselenocyanatoben-
zene and hydrazine hydrate were stirred in CH2Cl2 at room
temperature selenosemicarbazide 3a was afforded in high
yield.36 However, when 3a was treated with BTC in the
presence of NaOH for 12 h, only 35% of the desired product
4a was obtained (Table 1, entry 1). Other bases were evaluated
and NaHCO3 proved to be superior to NaOH, Na2CO3, Et3N
and Bu3N (entries 1–4). Other solvents such as toluene, EtOH,
ethyl acetate, H2O, 1,4-dioxane, THF and nitromethane were
also tried but lower yields resulted. Several ratios of base to
BTC were also studied and the best ratio of NaHCO3/BTC for
the reaction was 7.5:1. Furthermore, reaction temperature and
time were also examined. Although an increase of reaction
temperature would increase the reaction rate, it did not improve
the yield.
Bis(trichloromethyl) carbonate (BTC), as a bis-electrophilic
reagent, has proved to be safe and advantageous due to its low
vapour pressure and high stability. It has been successfully
employed as an efficient carbonyl activator for the one-
step cycloaddition with two types of nucleophiles. We have
studied BTC for several years and have explored some of its
applications.28–30
Addition of a base as an acid scavenger enhances the
reaction rate31–33 and the presence of a base could increase the
nucleophilicity of the reactants.
To the best of our knowledge, the preparation of 1,3,4-
selenadiazole derivatives is only described in two papers,34–35
and the preparation of 1,3,4-selenadiazol-ones has not been
reported. We now report a one-pot synthesis of novel 5-phenyl-
amino-1,3,4-selenadiazol-2(3H)-ones for the first time from
isoselenocyanates.
On the basis of these results, the optimal reaction conditions
for achieving the highest yield was carrying out the reaction in
CH2Cl2 at room temperature stirred at 7.5:1 ratio of NaHCO3
to BTC for 2 h. Under these optimised conditions, 5-phenyl-
amino-1,3,4-selenadiazol-2(3H)-one 4a was obtained in 83%
yield (Table 1, entry 7). The structure of the product was
confirmed by NMR, MS, HRMS and IR data.
Under the optimised reaction conditions, the scope of sub-
strates 1 and 2 (Scheme 2) was probed. Firstly, various alkyl-
isoselenocyanates were tested and the results are summarised
in Table 2. Generally, a higher yield was achieved when
an arylisoselenocyanate was used compared to its alkyl ana-
logue (Table 2, entries 1–6), and even better with an electron
donating group on the aromatic ring (entries 2–3). In addition,
phenylhydrazine instead of hydrazine hydrate was also investi-
gated (Table 2, entries 7–9). The reaction proceeded smoothly
at room temperature in good yields except for isoselenocyana-
tobenzene, which afforded the corresponding product 4g in
relatively low yield. Furthermore, introduction of an electron-
withdrawing group on the arylhydrazine decreased the
reaction yields (Table 2, compare entries 12–14 to entries 7, 9
and 11), and electron donating groups on the aromatic iso-
selenocyanate increased the reaction yield in reaction with
either 4-chlorophenylhydrazine or 4-methoxyphenylhydrazine
(Table 2, entries 12–17).
Results and discussion
When isoselenocyanatobenzene, hydrazine hydrate and BTC
were mixed in dichloromethane at room temperature for
several hours, TLC showed the formation of a new product
in low yield which was confirmed to be 5-(phenylamino)-
5-arylamino-1,3,4-selenadiazol-2(3H)-one (4a) (Scheme 1).
This result encouraged us to modify the reaction conditions to
improve the yield.
Scheme 1 One-pot synthesis of 5-(phenylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-one.
* Correspondent. E-mail: pharmlab@zjut.edu.cn

422 JOURNAL OF CHEMICAL RESEARCH 2012
Table 1 The optimisation of the reaction conditions for the
formation of 5-phenylamino-5-arylamino-1,3,4-selenadiazol-
2(3H)-one 4aa
Table 2 Preparation of 5-arylamino-3-aryl-5-arylamino-1,3,4-
selenadiazol-2(3H)-ones 4a–q from aryl isoselenocyanates 1a
Entry
R1
R2
Compound Products Yield/%b
Entry
Base
Solvents
Base/BTC
Yields/%b
1
2
Ph
p-Me-Ph
p-OMe-Ph
p-Cl-Ph
Cyclohexyl
n-Bu
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
83
88
94
85
70
62
57
85
88
80
75
57
62
58
78
75
69
1
2
NaOH
Et3N
Na2CO3
Bu3N
CH2Cl2
CH2Cl2
6.0:1
6.0:1
3.0:1
6.0:1
6.0:1
7.0:1
7.5:1
8.0:1
7.5:1
7.5:1
7.5:1
7.5:1
7.5:1
7.5:1
7.5:1
35
52
3
H
3
CH2Cl2
50
4
H
4
CH2Cl2
57
5
H
5
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
CH2Cl2
65
6
H
6
CH2Cl2
75
7
Ph
Ph
Ph
Ph
Ph
Ph
p-Cl-Ph
7
CH2Cl2
83
8
p-Me-Ph
p-OMe-Ph
p-Cl-Ph
o-Me-Ph
Ph
p-OMe-Ph p-Cl-Ph
o-Me-Ph p-Cl-Ph
p-OMe-Ph p-OMe-Ph
o-Me-Ph p-OMe-Ph
p-Cl-Ph p-OMe-Ph
8
CH2Cl2
81
9
9
toluene
CH3CH2OH
AcOEt
53
10
11
12
13
14
15
16
17
10
11
12
13
14
15
Trace
68
H2O
0
26
Trace
35
1,4-dioxane
THF
CH3NO2
a The reaction was monitored by TLC.
b Isolated yields based on isoselenocyanatobenzene.
a The reactions were carried out in the presence of isoseleno-
cyanates (R≡N=C=Se, 1 mmol), hydrazines (R2NHNH2, 1 mmol),
BTC (0.33 mmol) and NaHCO3 (2.5 mmol) in CH2Cl2 at r.t. for
2 h.
Based on the results described, we propose a plausible
mechanism (Scheme 3). Nucleophilic addition of the amino
group of the hydrazines 2 to isoselenocyanates 1 leads to the
adduct intermediate 3, which then reacts with the bis-electro-
philic reagent BTC to form intermediate 5. In the presence
of sodium bicarbonate, the intermediate 5 undergoes a
cyclisation to afford the final heterocycle 4.
In conclusion, we used the tandem reaction of arylisosele-
nocyanates, hydrazine and BTC to synthesise selenium-
containing heterocycles. A variety of 5-arylamino-1,3,4-sele-
nadiazol-2-ones could be prepared in good yields in the
presence of sodium bicarbonate by this simple, convenient and
efficient procedure. The use of NaHCO3, the short reaction
time, mild reaction conditions, green-chemistry features
and commercially available starting materials offer specific
advantages of the method.
b Isolated yields based on isoselenocyanates.
Experimental
Melting points were determined using a Büchi B-540 apparatus and
are uncorrected. IR Spectra: Nicolet Avatar-370 spectrometer, in KBr;
υ in cm−1. 1H and 13C NMR Spectra: Varian Mercury Plus-400 instru-
ment, in (d6) DMSO or CDCl3 at 400 and 100 MHz, resp.; δ in ppm,
J in Hz. ESI-MS: Thermo Finnigan LCQ Advantage (ESI) or Trace
DSQ (EI) instrument; in m/z. HRMS: Agilent 6210 TOF instrument.
Synthesis of 5-arylamino-1,3,4-selenadiazol-2(3H)-ones; typical
procedure
To a dichloromethane solution of isoselenocyanatobenzene 1a
(0.182 g, 1 mmol) was added 85% hydrazine hydrate (0.059 g,
1 mmol) at room temperature. After the reaction was complete
(monitored by TLC, 30 min), NaHCO3 (0.210 g, 2.5 mmol) and
Scheme 2 Preparation of 5-arylamino-5-arylamino-1,3,4-selenadiazol-2(3H)-ones 4a-q from aryl isoselenocyanates.
Scheme 3 A plausible mechanism proposed for the formation of 4.

JOURNAL OF CHEMICAL RESEARCH 2012 423
bis (trichloromethyl) carbonate (0.1g, 0.33 mmol) were added. The
reaction mixture was stirred for 1.5 h. The mixture was washed with
water and the organic layer was separated, dried over MgSO4, and
evapourated. The residue was subjected to column chromatography
on silica gel using petroleum ether:AcOEt = 8:1 to 4:1 as eluent
system, affording 4a (0.199 g, 83%) as colourless crystals.
5-(Phenylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-one (4a):
Colourless crystals; yield, 83%; m.p. 168.1–168.8 °C; IR: νmax = 3139,
1669, 1599, 1577, 1548, 1401, 1319, 1253, 751 cm−1; 1H NMR
(DMSO-d6): δ 11.63 (s, 1H, NH), 9.67 (s, 1H, NH), 7.40 (dd, J1 =
0.8 Hz, J2 = 8.4 Hz, 2H, ArH), 7.28 (t, J = 8.4 Hz, 2H, ArH), 6.94 (t,
J = 7.2 Hz, 1H, ArH); 13C NMR (DMSO-d6): δ 171.4 (C=O), 149.5
(C=N), 140.7, 128.9 (CH×2), 121.3, 117.0 (CH×2); EI-MS: 243 (18),
241 (92, M+), 239 (46), 237 (23), 77 (100); HRMS-ESI: Calcd for
C8H8N3OSe (M+H)+ 241.9833; found: 241.9826.
5-(4-Methylphenylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-one
(4b): Yellow solid; yield, 88%; m.p. 150.2–150.7 °C; IR: νmax = 3161,
1665, 1595, 1568, 1515, 1401, 1309, 1229, 1102, 814 cm−1; 1H NMR
(DMSO-d6): δ 11.56 (s, 1H, NH), 9.55 (s, 1H, NH), 7.28 (d, J =
8.4 Hz, 2H, ArH), 7.08 (d, J = 8.4 Hz, 2H, ArH), 2.23 (s, 3H, CH3); 13C
NMR (DMSO-d6): δ 171.4 (C=O), 149.6 (C=N), 138.3, 130.2, 129.3
(CH×2), 117.2 (CH×2), 20.3 (CH3); ESI-MS: m/z (%) = 258 (10), 256
(100, M+ +1), 254 (5); HRMS-ESI: Calcd for C9H8N3OSe (M-H)−
253.9833; found: 253.9841.
2H, ArH), 2.25 (s, 3H, CH3); 13C NMR (DMSO-d6): δ 168.1 (C=O),
147.4 (C=N), 138.3, 137.8, 131.0, 129.5 (CH×2), 129.0 (CH×2),
126.1, 121.9 (CH×2), 117.6 (CH×2), 20.3 (CH3); ESI-MS: m/z (%) =
332 (20), 330 (100, M− -1), 328 (50), 326 (22); HRMS-ESI: Calcd for
C15H14N3OSe (M+H)+ 332.0302; found: 332.0295.
5-(4-Methoxyphenylamino)-3-phenyl-5-arylamino-1,3,4-selenadiazol-
2(3H)-one (4i): Pink solid; yield, 88%; m.p. 155.0–155.7 °C; IR: νmax
= 3422, 3131, 1660, 1599, 1570, 1509, 1400, 1250, 1033, 840 cm−1;
1H NMR (DMSO-d6): δ 9.76 (s, 1H, NH), 7.76 (d, J = 8.0 Hz, 2H,
ArH), 7.47 (t, J = 8.4 Hz, 2H, ArH), 7.42 (d, J = 8.8 Hz, 2H, ArH),
7.29 (t, J = 7.2 Hz, 1H, ArH), 6.93 (d, J = 8.8 Hz, 2H, ArH), 3.73
(s, 3H, OCH3); 13C NMR (DMSO-d6): δ 168.0 (C=O), 154.5 (C=N),
147.6, 138.3, 133.6, 128.9 (CH×2), 126.0, 121.9 (CH×2), 119.2
(CH×2), 114.3 (CH×2), 55.2 (OCH3); EI-MS: m/z (%) = 349 (20), 347
(100, M+), 345 (50); HRMS-ESI: Calcd for C15H14N3O2Se (M+H)+
348.0251; found: 348.0247.
5-(4-Chlorophenylamino)-3-phenyl-5-arylamino-1,3,4-selenadiazol-
2(3H)-one (4j): Yellow crystals; yield, 80%; m.p. 246.0–246.6 °C; IR:
νmax = 3320, 3196, 3125, 1665, 1651, 1574, 1541, 1490, 1403, 1313,
1251, 1094, 817, 686 cm−1; 1H NMR (DMSO-d6): δ 10.10 (s, 1H, NH),
7.75 (dd, J1 = 1.2 Hz, J2 = 8.4 Hz, 2H, ArH), 7.52–7.47 (m, 4H, ArH),
7.39 (d, J = 9.2 Hz, 2H, ArH), 7.32 (t, J = 7.2 Hz, 1H, ArH); 13C
NMR (DMSO-d6): δ 168.1 (C=O), 147.1 (C=N), 139.1, 138.1, 129.0
(CH×4), 126.3, 125.4, 122.1 (CH×2), 118.9 (CH×2); EI-MS: m/z (%)
= 353 (40), 351 (100, M+), 349 (50), 347 (22); HRMS-ESI: Calcd for
C14H9ClN3OSe (M-H)− 349.9599; found: 349.9585.
5-(2-Methylphenylamino)-3-phenyl-5-arylamino-1,3,4-selenadiazol-
2(3H)-one (4k): Yellow solid; yield,75%; m.p. 132.2–133.1 °C; IR:
νmax = 3358, 1658, 1578, 1535, 1455, 1255, 1093, 747, 693 cm−1; 1H
NMR (DMSO-d6): δ 9.08 (s, 1H, NH), 7.84 (d, J = 7.6 Hz, 1H, ArH),
7.71 (d, J = 8.0 Hz, 1H, ArH), 7.45 (t, J = 7.6 Hz, 2H, ArH), 7.33–7.25
(m, 2H, ArH), 7.23–7.18 (m, 2H, ArH), 7.00 (t, J = 7.2 Hz, 1H, ArH),
2.30 (s, 3H, CH3); 13C NMR (DMSO-d6): δ 168.8 (C=O), 148.9 (C=N),
138.4, 138.3, 130.8, 129.0 (CH×2), 128.5, 126.7, 126.2, 123.7, 122.1
(CH×2), 120.9, 18.2 (CH3); ESI-MS: m/z (%) = 332 (19), 330 (100,
M− -1), 328 (44); HRMS-ESI: Calcd for C15H13N3OSeNa (M+Na)+
354.0122; found: 354.0125.
5-(4-Methoxyphenylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-
one (4c): Pink solid; yield, 94%; m.p. 133.8–134.4 °C; IR: νmax
=
3156, 1668, 1606, 1578, 1510, 1401, 1248, 1033, 824 cm−1; 1H NMR
(DMSO-d6): δ 11.52 (s, 1H, NH), 9.46 (s, 1H, NH), 7.32 (d, J =
8.8 Hz, 2H, ArH), 6.87 (d, J = 8.8 Hz, 2H, ArH), 3.71 (s, 3H, OCH3);
13C NMR (DMSO-d6): δ 171.3 (C=O), 154.1 (C=N), 150.0, 134.2,
118.9 (CH×2), 114.2 (CH×2), 55.2 (OCH3); ESI-MS: m/z (%) = 272
(17), 270 (100, M− -1), 268 (37), 267 (26), 266 (20); HRMS-ESI:
Calcd for C9H9N3O2SeNa (M+Na)+ 293.9758; found: 293.9752.
5-(4-Chlorophenylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-one
(4d): Yellow crystals; yield, 85%; m.p. 183.0–183.8 °C; IR: νmax
=
3301, 3199, 3130, 1664, 1639, 1578, 1545, 1491, 1403, 1319, 1258,
1
1102, 816 cm−1; H NMR (DMSO-d6): δ 11.70 (s, 1H, NH), 9.82 (s,
1H, NH), 7.43 (d, J = 8.8 Hz, 2H, ArH), 7.33 (d, J = 8.8 Hz, 2H, ArH);
13C NMR (DMSO-d6): δ 171.4 (C=O), 149.2 (C=N), 139.6, 128.8
(CH×2), 124.7, 118.5 (CH×2); EI-MS: m/z (%) = 277 (40), 275 (92,
M+), 273 (50), 271 (20), 218 (100); HRMS-ESI: Calcd for
C8H7ClN3OSe (M+H)+ 275.9443; found: 275.9435.
3-(4-ChloroPhenyl)-5-(phenylamino)-5-arylamino-1,3,4-selenadiazol-
2(3H)-one (4l): Yellow solid; yield, 57%; m.p. 194.5–194.9 °C;
IR: νmax = 3415, 3149, 1659, 1614, 1483, 1401, 1363, 1298, 1086,
1
838 cm−1; H NMR (DMSO-d6): δ 9.98 (s, 1H, NH), 7.82 (d, J =
9.2 Hz, 2H, ArH), 7.55 (d, J = 9.2 Hz, 2H, ArH), 7.48 (d, J = 8.8 Hz,
2H, ArH), 7.35 (t, J = 7.6 Hz, 2H, ArH), 7.02 (t, J = 7.6 Hz, 1H, ArH);
13C NMR (DMSO-d6): δ 168.3 (C=O), 147.5 (C=N), 140.1, 137.0,
129.8, 129.1 (CH×2), 128.9 (CH×2), 123.3 (CH×2), 122.1, 117.5
(CH×2); ESI-MS: m/z (%) = 352 (42), 350 (100, M− -1), 348 (48),
346(16);HRMS-ESI:CalcdforC14H10ClN3OSeNa(M+Na)+ 373.9575;
found: 373.9564.
5-(Cyclohexylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-one
(4e): Colourless solid; yield, 70%; m.p. 142.2–142.8 °C; IR: νmax
=
3441, 3184, 2929, 2849, 1661, 1595, 1400, 1322, 1086 cm−1; 1H NMR
(DMSO-d6): δ 11.08 (s, 1H, NH), 6.94 (d, J = 7.2 Hz, 1H, NH), 3.39–
3.34 (m, 1H, CH), 1.92–1.87 (m, 2H, CH2), 1.69–1.65 (m, 2H, CH2),
1.55–1.51 (m, 1H, CH2), 1.31–1.12 (m, 5H, CH2); 13C NMR (DMSO-
d6): δ 171.6 (C=O), 152.8 (C=N), 51.7, 32.4 (CH2×2), 25.3, 24.2
(CH2×2); ESI-MS: m/z (%) = 248 (17), 246 (100, M− -1), 244 (43),
242(12); HRMS-ESI: Calcd for C8H13N3OSeNa (M+Na)+ 270.0122;
found: 270.0117.
3-(4-Chlorophenyl)-5-(4-methoxyphenylamino)-5-arylamino-1,3,4-
selenadiazol-2(3H)-one (4m): Yellow solid; yield, 62%; m.p. 194.2–
194.6 °C; IR: νmax = 3342, 1665, 1599, 1550, 1509, 1401, 1253, 1086,
1
1033, 822 cm−1; H NMR (DMSO-d6): δ 9.79 (s, 1H, NH), 7.81 (d,
5-(Butylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-one (4f): Oil;
yield, 62%; IR: νmax = 3420, 1651, 1552, 1384, 1048, 1025, 1001 cm−1;
1H NMR (DMSO-d6): δ 11.13 (s, 1H, NH), 6.99 (s, 1H, NH), 3.11–
3.07 (m, 2H, CH2N), 1.50–1.44 (m, 2H, CH2), 1.34–1.29 (m, 2H,
CH2), 0.88 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (DMSO-d6): δ 171.5
(C=O), 153.7 (C=N), 42.5, 30.6, 19.6, 13.6; EI-MS: m/z (%) = 223
(10), 221 (50, M+), 219 (25), 217(13), 66 (100); HRMS-ESI: Calcd for
C6H12N3OSe (M+H)+ 222.0146; found: 222.0140.
3-Phenyl-5-(phenylamino)-5-arylamino-1,3,4-selenadiazol-2(3H)-one
(4g): Purple solid; yield, 57%; m.p. 174.5–175.3 °C; IR: νmax = 3425,
3154, 1661, 1601, 1571, 1400, 1343, 1294, 706 cm−1; 1H NMR
(DMSO-d6): δ 9.95 (s, 1H, NH), 7.78–7.75 (m, 2H, ArH), 7.51–7.47
(m, 4H, ArH), 7.36–7.29 (m, 3H, ArH), 7.00 (t, J = 7.2 Hz, 1H, ArH);
13C NMR (DMSO-d6): δ 168.1 (C=O), 147.2 (C=N), 140.2, 138.2,
129.1 (CH×2), 128.9 (CH×2), 126.1, 122.0 (CH×3), 117.4 (CH×2);
ESI-MS: m/z (%) = 318 (19), 316 (100, M− -1), 314 (45), 312 (17);
HRMS-ESI: Calcd for C14H12N3OSe (M+H)+ 318.0146; found:
318.0140.
J = 8.8 Hz, 2H, ArH), 7.53 (d, J = 8.8 Hz, 2H, ArH), 7.41 (d, J =
9.2 Hz, 2H, ArH), 6.93 (d, J = 9.2 Hz, 2H, ArH), 3.73 (s, 3H, OCH3);
13C NMR (DMSO-d6): δ 168.1 (C=O), 154.6 (C=N), 147.8, 137.1,
133.5, 129.7, 128.8 (CH×2), 123.2 (CH×2), 119.3 (CH×2), 114.3
(CH×2), 55.2 (OCH3); ESI-MS: m/z (%) = 382 (44), 381 (15), 380
(100, M− -1), 378 (46); HRMS-ESI: Calcd for C15H13ClN3O2Se
(M+H)+ 381.9862; found: 381.9850.
3-(4-Chlorophenyl)-5-(2-methylphenylamino)-5-arylamino-1,3,4-
selenadiazol-2(3H)-one (4n): Pink solid; yield,58%; m.p. 168.3–
169.2 °C; IR: vmax = 3382, 1662, 1588, 1538, 1489, 1455, 1304, 1256,
1
825, 740 cm−1; H NMR (DMSO-d6): δ 9.11 (s, 1H, NH), 7.83 (d,
J = 8.0 Hz, 1H, ArH), 7.76 (d, J = 8.8 Hz, 2H, ArH), 7.51 (d, J =
8.8 Hz, 2H, ArH), 7.24–7.19 (m, 2H, ArH), 7.02 (t, J = 7.6 Hz, 1H,
ArH), 2.29 (s, 3H, CH3); 13C NMR (DMSO-d6): δ 168.7 (C=O), 149.0
(C=N), 138.1, 137.1, 130.6, 129.7, 128.8 (CH×2), 128.5, 126.5, 123.7,
123.2 (CH×2), 121.0, 18.0 (CH3); ESI-MS: m/z (%) = 402 (62);
400 (100, M− + Cl), 398 (45), 366 (30), 364 (75, M− -1), 362 (33);
HRMS-ESI: Calcd for C15H12ClN3OSeNa (M+Na)+ 387.9732; found:
387.9723.
5-(4-Methylphenylamino)-3-phenyl-5-arylamino-1,3,4-selenadiazol-
2(3H)-one (4h): Yellow solid; yield, 85%; m.p. 176.8–177.4 °C; IR:
νmax = 3330, 3130, 1665, 1598, 1543, 1512, 1401, 1301, 1253, 1094,
3-(4-Methoxyphenyl)-5-(4-methoxyphenylamino)-5-arylamino-
1,3,4-selenadiazol-2(3H)-one (4o): Pink solid; yield:78%; m.p.
151.7–153.2 °C; IR: vmax = 3419, 3242, 1656, 1597, 1571, 1509, 1298,
1
813, 751, 689 cm−1; H NMR (DMSO-d6): δ 9.85 (s, 1H, NH), 7.75
(d, J = 7.6 Hz, 2H, ArH), 7.48 (t, J = 8.0 Hz, 2H, ArH), 7.37 (d, J =
8.4 Hz, 2H, ArH), 7.30 (t, J = 7.2 Hz, 1H, ArH), 7.14 (d, J = 8.4 Hz,
1
1254, 1033, 833 cm−1; H NMR (CDCl3): δ 8.09 (s, 1H, NH), 7.86

424 JOURNAL OF CHEMICAL RESEARCH 2012
6
7
8
9
M. Koketsu, H.O. Yang, Y.M. Kim, M. Ichihashi and H. Ishihara, Org.
Lett., 2001, 3, 1705.
B.D. Johnston, A. Ghavami, M.T. Jensen, B. Svensson and B.M. Pinto,
J. Am. Chem. Soc., 2002, 124, 8245.
A.K. Sharma, A. Sharma, D. Desai and S.V. Madhunapantula, J. Med.
Chem., 2008, 51, 7820.
R. Terazawa, D.R. Garud, N. Hamada, Y. Fujita and T. Itoh, Bioorg. Med.
Chem., 2010, 18, 7001.
(d, J = 9.2 Hz, 2H, ArH), 7.51 (d, J = 9.2 Hz, 2H, ArH), 7.06 (d,
J = 9.2 Hz, 2H, ArH), 7.02 (d, J = 9.2 Hz, 2H, ArH), 3.88 (s, 3H,
OCH3), 3.87 (s, 3H, OCH3); 13C NMR (CDCl3): δ 162.2 (C=O), 160.5
(C=N), 159.7, 141.4, 131.5, 127.9 (CH×2), 127.7, 126.7 (CH×2),
114.7 (CH×2), 114.0 (CH×2), 55.6 (OCH3), 55.5 (OCH3); ESI-MS:
m/z (%) = 378 (20), 376 (100, M− -1), 374 (46); HRMS-ESI: Calcd for
C16H15N3O3SeNa (M+Na)+ 400.0176; found: 400.0165.
3-(4-Methoxyphenyl)-5-(2-methylphenylamino)-5-arylamino-1,3,4-
selenadiazol-2(3H)-one (4p): Pink solid; yield,75%; m.p. 140.6–
142.1 °C; IR: vmax = 3378, 1660, 1582, 1540, 1509, 1251, 1094, 830,
741 cm−1; 1H NMR (CDCl3): δ 7.63 (d, J = 9.2 Hz, 2H, ArH), 7.45 (d,
J = 7.2 Hz, 1H, ArH), 7.23 (t, J = 7.2 Hz, 2H, ArH), 7.11 (t, J = 7.2 Hz,
1H, ArH), 6.93 (d, J = 9.2 Hz, 2H, ArH), 6.40 (s, 1H, NH), 3.83 (s, 3H,
OCH3), 2.33 (s, 3H, CH3); 13C NMR (CDCl3): δ 167.7 (C=O), 157.7
(C=N), 150.4, 137.6, 131.1, 130.8, 129.5, 126.9, 124.9, 124.0 (CH×2),
121.1, 113.7 (CH×2), 55.1 (OCH3), 17.4 (CH3); ESI-MS: m/z (%) =
362 (21), 360 (100, M− -1), 358 (51); HRMS-ESI: Calcd for
C16H15N3O2SeNa (M+Na)+ 384.0227; found: 384.0224.
10 J.H. Zhang and Y. Cheng, Org. Biomol. Chem., 2009, 7, 3264.
11 E. Ibañez, D. Plano, M. Font, C. Calvo, C. Prior and J.A. Palop, Eur. J.
Med. Chem., 2011, 46, 265.
12 S.H. Abdel-Hafez, Eur. J. Med. Chem., 2008, 43, 1971.
13 M. Scholz, H.K. Ulbrich and G. Dannhardt, Eur. J. Med. Chem., 2008, 43,
1152.
14 A.V. Karnik, A.M. Kulkarni, N.J. Malviya, B.R. Mourya and B.L. Jadhav,
Eur. J. Med. Chem., 2008, 43, 2615.
15 K. Sivapriya, P. Suguna, A. Banerjee, V. Saravanan, D.N. Rao and
S. Chandrasekaran, Bioorg. Med. Chem., 2007, 17, 6387.
16 D. Plano, Y. Baquedano, D. Moreno-Mateos and M. Font, Eur. J. Med.
Chem., 2011, 46, 3315.
17 S. Ueda, H. Terauchi, K. Suzuki, A. Yano, M. Matsumoto and T. Kubo,
Bioorg. Med. Chem. Lett., 2005, 15, 1361.
18 S. Kumar, H. Johansson, L. Engman, L. Valgimigli, R. Amorati,
M.G. Fumo and G.F. Pedulli, J. Org. Chem., 2007, 72, 2583.
19 S.U. Hossain, S. Sengupta and S. Bhattacharya, Bioorg. Med. Chem., 2005,
13, 5750.
20 G.L. Sommen, A. Linden and H. Heimgartner, Helv. Chim. Acta, 2007, 90,
1849.
21 G.L. Sommen, A. Linden and H. Heimgartner, Eur. J. Org. Chem., 2005,
14, 3128.
5-(4-Chlorophenylamino)-3-(4-methoxyphenyl)-5-arylamino-1,3,4-
selenadiazol-2(3H)-one (4q): Red solid; yield,69%; m.p. 133.4–
134.8 °C; IR: νmax = 3341, 1667, 1580, 1533, 1509, 1244, 1096, 826
1
740 cm−1; H NMR (DMSO-d6): δ 10.03 (s, 1H, NH), 7.57 (d, J =
8.8 Hz, 2H, ArH), 7.46 (d, J = 8.8 Hz, 2H, ArH), 7.34 (d, J = 8.8 Hz,
2H, ArH), 7.00 (d, J = 8,8 Hz, 2H, ArH), 3.78 (s, 3H, OCH3); 13C
NMR (DMSO-d6): δ 167.5 (C=O), 157.2 (C=N), 146.7, 138.9, 131.0,
128.7 (CH×2), 125.1, 124.1 (CH×2), 118.6 (CH×2), 113.9 (CH×2),
55.3 (OCH3); ESI-MS: m/z (%) = 382 (43), 380 (100, M− -1), 378
(52); HRMS-ESI: Calcd for C15H12ClN3O2SeNa (M+Na)+ 403.9681;
found: 403.9675.
22 P.K. Atanassov, A. Linden and H. Heimgartner, Helv. Chim. Acta, 2004, 87,
1873.
23 P.K. Atanassov, A. Linden and H. Heimgartner, Helv. Chim. Acta, 2003, 86,
3235.
24 Y.H. Zhou, A. Linden and H. Heimgartner, Helv. Chim. Acta, 2000, 83,
1576.
25 P.K. Atanassov, Y.H. Zhou, A. Linden and H. Heimgartner, Helv. Chim.
Acta, 2002, 85, 1102.
26 Ó. López, S. Maza, V. Ulgar, I. Maya and J.G. Fernández-Bolaños,
Tetrahedron, 2009, 65, 2556.
We are grateful to the National Natural Science Foundation of
China (No. 200906083) and Natural Science Foundation of
Zhejiang Province (No. Y40900488) for financial support. We
also thank Dr Y. M. Ma for helpful discussions.
27 J.G. Fernández-Bolaños, Ó. López, V. Ulgar, I. Maya and J. Fuentes,
Tetrahedron Lett., 2004, 45, 4081.
28 W.K. Su and C. Jin, Org. Lett., 2007, 9, 993.
29 W.K. Su, Y. Zhang, J.J. Li and P. Li, Org. Prep. Proced. Int., 2008, 40,
543.
Received 16 January 2012; accepted 26 April 2012
Paper 1201141 doi: 10.3184/174751912X13377840596361
Published online: 26 June 2012
30 Z.H. Li, C. Zheng and W.K. Su, J. Heterocyclic Chem., 2008, 45, 1195.
31 G.L. Sommen, A. Linden and H. Heimgartner, Tetrahedron, 2006, 62,
3344.
32 K. Sivapriya, P. Suguna, A. Banerjee, V. Saravanan, D.N. Rao and
S. Chandrasekaran, Bioorg. Med. Chem., 2007, 17, 6387.
33 G.L. Sommen, A. Linden and H. Heimgartner, Lett. Org. Chem., 2007, 4,
7.
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