An efficient one-pot synthesis of 2-amino-1,3,4-selenadiazoles

Article abstract of DOI:10.3184/174751916X14558161990884

An efficient one-pot synthesis of 2-amino-1,3,4-selenadiazoles from isoselenocyanates, hydrazine hydrate and aromatic aldehydes has been developed. This approach provides a simple, mild and facile way to construct various derivatives in moderate to good y

Full text of DOI:10.3184/174751916X14558161990884

178 RESEARCH PAPER
VOL. 40 MARCH, 178–181
JOURNAL OF CHEMICAL RESEARCH 2016
An efficient one-pot synthesis of 2-amino-1,3,4-selenadiazoles
Xue Lia, Bin Gana, Tinghui Xiea, Ping Yangb and Yuanyuan Xiea,b*
aCollaborative Innovation Centre of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P.R. China
bKey Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou
310014, P.R. China
An efficient one-pot synthesis of 2-amino-1,3,4-selenadiazoles from isoselenocyanates, hydrazine hydrate and aromatic aldehydes has
been developed. This approach provides a simple, mild and facile way to construct various derivatives in moderate to good yields (57–
82%). A plausible mechanism is proposed for the formation of the target products.
Keywords: isoselenocyanates, selenosemicarbazides, selenohydrazones, selenoheterocycle, selenadiazoles
Selenium-containing heterocycles have been recognised to play
an important role in both synthetic chemistry1,2 and medicinal
biology as biological response modifiers.3–6 As five-membered
selenium-containing heterocycles, 1,3,4-selenadiazoles have
been studied for decades due to their potential anti-bacterial,
anti-tumour, anti-convulsant and anti-inflammatory activities.7,8
Besides, some 1,3,4-selenadiazoles have been reported as
thermotropic liquid crystals and metal ion complexation
reagents.9–12 As a result, a variety of approaches have been
developed to synthesise 1,3,4-selenadiazoles. Stolle13 obtained
1,3,4-selenadiazoles from reacting 1,2-diacetylhydrazine with
phosphorus pentaselenide. Kendall14 reported the reaction
of dimethylformamide azine with hydrogen selenide to
form 1,3,4-selenadiazoles. In 1973, Bulka15,16 et al. prepared
2-(arylamino)-5-aryl-1,3,4-selenadiazoles or 2,5-diamino-
1,3,4-selenadiazoles from the cyclodehydration of RNH(C=Se)
NHNHCOR′ or RNH(C=Se)NHNH(C=Se)NHR′ (R, R′ = H,
Me, Ar) in concentrated H2SO4 or Ac2O. Cohen17 described
a method for the synthesis of 1,3,4-selenadiazoles from
selenobenzamides with hydrazine hydrate. In 2009, Hua et al.18
one-pot synthesis of 2-amino-1,3,4-selenadiazoles from
isoselenocyanates, hydrazine hydrate and aromatic aldehydes
(Scheme 1). This approach provides a simple, mild and facile
way to construct various 2-amino-1,3,4-selenadiazoles in
moderate to good yields (57–82%).
Result and discussion
Initially, phenyl selenohydrazone (4a) was selected to optimise
the ring-closure reaction conditions. The effects of solvent,
reaction temperature, the amount of N-bromosuccinimide
(NBS) and different bases were investigated. The results are
shown in Table 1. Among all the solvents CH
2Cl2 proved to be
the optimal one since a 71% yield could be obtained (Table 1,
entries 1–5). Unfortunately, deselenisation was observed when
THF or CH3CN was used as the solvent. The reaction proceeded
more efficiently at 40 °C (reflux) than at 35 °C (Table 1, entries
5 and 6). Prolonged reaction times at 40 °C did not greatly
enhance the yield (Table 1, entry 7). The reaction failed
completely in the absence of base (Table 1, entry 8). Various
bases, such as NaOAc, NaHCO3, Na2CO3 and triethylamine
(TEA) were investigated and NaOAc was found to be the most
promising (Table 1, entries 5, 9–11). To further improve the
yield, the effect of altering the amount of NBS was investigated
(Table 1, entries 5, 13 and 14). The yield was improved to 85%
by increasing the amount of NBS to 1.5 equiv. Furthermore,
there was no product in the absence of NBS (Table 1, entry 12).
So, the optimal reaction conditions were established as using
1.5 equiv. of NBS, NaOAc as base and CH2Cl2 as solvent under
reflux.
used
2,4-diphenyl-1,3-diselenadiphosphetane-2,4-diselenide
(Woollins’ reagent) as selenation reagent to react with
1,2-diacylhydrazines to prepare 1,3,4-selenadiazoles. However,
all the procedures to date have severe environmental or safety
concerns as they involve toxic reagents such as hydrogen
selenide, high reaction temperatures and tedious manipulative
procedures.
Isoselenocyanates were widely employed in the synthesis
of selenium-containing heterocycles due to their convenient
preparation, low toxicity, relative stability and excellent
reactivity.19–23 We have been interested in the synthesis of
1,3,4-selenadiazoles. Very recently, we developed an efficient
With the optimised conditions in hand, we set out to explore
the substrate scope. Selenosemicarbazides 2 could be prepared
conveniently from isoselenocyanates 1a–e24,25 and hydrazine
O
R2
H
H
H
N
3
R1
N
N
C
R1
NH2
solvent
r.t.
+
Se
NH2NH2 H2O
AcOH,r.t.
Se
1
2
H
H
H
R2
Se
N
N
N
NBS
R2
R1
N
R1
base,Temp.
N N
Se
4
5
Scheme 1 Preparation of 2-amino-1,3,4-selenadiazoles from isoselenocyanates, hydrazine hydrate and aldehydes.
* Correspondent. E-mail: xyycz@zjut.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2016 179
Table 1 Optimisation of reaction conditions for the synthesis of 2-amino-
1,3,4-selenadiazoles via cycloselenisation
Table 2 One-pot synthesis of 2-amino-1,3,4-selenadiazoles 5 from
isoselenocyanates, hydrazine hydrate and aldehydes 3
O
H
H
H
Se
N
N
N
R2
H
solvent, base
NBS,Temp.
H
H
N
N
3
R1
N
N
C
N
N
R1
NH2
CH2Cl2
r.t.
Se
4a
+
Se
NH2NH2 H2O
AcOH,r.t.
5a
Se
1
2
Base
NBS
Temp. Timea Yieldb
1a: R1= C6H5; 1b: R1= 4-ClC6H4;
3a: R2 = C6H5; 3b: R2= 4-ClC6H4;
Entry Solvent
(2.0 equiv.)
NaOAc
(equiv.)
1.4
/°C
40
/h
12
/%
< 10
20
1c: R1= 4-CH3C6H4; 1d: R1= 4-CH3OC6H4; 3c: R2= 4-CH3C6H4; 3d: R2= 4-CH3OC6H4;
1e: R1= Cyclohexyl;
3e: R2= 3-CH3OC6H4; 3f: R2= 2-ClC6H4;
1
2
CH3CN
EtOAc
NaOAc
ClCH2CH2Cl NaOAc
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
none
1.5
1.6
40
40
40
reflux
35
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
12
12
12
2
12
12
12
2
2
2
12
2
2
3
60
trace
71
75
80
none
trace
trace
< 10
none
85
H
H
H
R2
Se
N
N
N
NaOAc
R1
N
R2
4
THF
NaOAc
NaOAc
NaOAc
NaOAc
none
Na2CO3
NaHCO3
TEA
R1
N N
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
NBS, reflux
Se
4
5
Entry
1
2
3
4
R1
R2
C6H5
Productsa Yieldb/%
C6H5
C6H5
C6H5
C6H5
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
73
71
78
77
57
77
79
64
71
79
80
78
81
82
74
60
9
4-ClC6H4
4-CH3C6H4
3-CH3OC6H4
C6H5
10
11
12
13
14
NaOAc
NaOAc
NaOAc
5
4-ClC6H4
6
7
8
9
10
11
12
13
14
15
16
4-CH3C6H4
4-CH3OC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
Cyclohexyl
C6H5
C6H5
85
aMonitored by TLC.
bIsolated yield based on 4a.
2-ClC6H4
4-ClC6H4
3-CH3OC6H4
4-CH3OC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
C6H5
hydrate, then further reacted with aldehyde 3 to form the
corresponding selenohydrazones 4 under AcOH catalysis in
CH2Cl2 at room temperature. Subsequently, 2-amino-1,3,4-
selenadiazoles 5 could be observed after NaOAc and NBS were
directly added to the above mixture in one pot and then heated to
reflux. The results are summarised in Table 2. Various 2-amino-
1,3,4-selenadiazoles were prepared in moderate to good yields
(57–82%). The nature of the R2 group on the aldehydes 3
affected the reaction yields to some degree (Table 2, entries 1–4).
Aldehydes substituted with electron-donating groups [Table 2,
entries 3 (78%) and 4 (77%)] provided slightly higher yields than
those having an electron-withdrawing group [Table 2, entry 2
(71%)]. The substituents on the isoselenocyanates also affected
the reaction yields. Thus, isoselenocyanates with electron-
donating substituents (Table 2, entries 6 and 7) afforded higher
yields than those with an electron-withdrawing substituent
(Table 2, entry 5). Therefore, 2-amino-1,3,4-selenadiazoles 5
could be obtained with the best yields (79–82%) when R1 and
R2 were both electron-donating groups (Table 2, entries 10–14).
However, when aldehyde 3f reacted with isoselenocyanate (1c)
(Table 2, entry 8), the yield decreased due to the steric effect,
compared with aldehydes 3b (Table 2, entry 9). Cyclohexyl
isoselenocyanate (1e) also provided the desired product in 60%
yield (Table 2, entry 16).
aConfirmed by IR, 1H and 13C NMR, MS-ESI, HRMS-ESI.
bIsolated yield based on 1.
A plausible mechanism is proposed for the formation of 2-amino-
1,3,4-selenadiazoles 5 in Scheme 2. Firstly, selenosemicarbazides
2, generated rapidly and efficiently from isoselenocyanates 1
and hydrazine hydrate, reacted with aldehydes 3 to form the
selenohydrazones 4. Subsequently, selenohydrazones 4 were
attacked by NBS and converted to the intermediate selenenyl
bromide (6). Then the iminoselenadiazoles 7 were obtained via
intramolecular cyclisation of 6 using NaOAc as base and could then
aromatise (following a prototropic shift) directly to the products 5.
Conclusion
In conclusion, a facile and efficient one-pot synthesis of
2-amino-1,3,4-selenadiazoles 5 has been developed starting
O
3
H
N
H
H
H
N
R1
O
N
R2
H
N
N
C
R1
N
R2
R1
NH2
+
Se
NH2NH2 H2O
1
e
S
2
4
Se
H2O
AcO
H
O
H
N
N N
R2
Se
H
R2
N N
N
R1
R1
R1
R2
Br
N
N
N N
Se
Se
6
7
5
Br
Scheme 2 Plausible mechanism proposed for the formation of 5.

180 JOURNAL OF CHEMICAL RESEARCH 2016
141.2, 134.4, 129.9, 129.6, 124.0, 120.5, 118.5, 116.2, 111.9, 55.5; MS
(ESI) m/z (%): 330 (48), 332 ([M + H]+, 100); HRMS-ESI calcd for
C15H14N3O80Se: (M + H)+: 332.0297; found: 332.0287.
from isoselenocyanates 1, hydrazine hydrate and aromatic
aldehydes 3 in moderate to good yields. The procedure obviates
the need to isolate the two intermediates 2 and 4. This method
possesses the advantages of short reaction times, mild reaction
conditions and good tolerance of functional groups, making it
an attractive procedure for the for the synthesis of 2-amino-
1,3,4-selenadiazoles 5.
2-(4-Chlorophenylamino)-5-phenyl-1,3,4-selenadiazole (5e): Yellow
solid; yield 57%; m.p. 218.1–220.0 °C; IR (KBr) (nmax cm–1): 3442, 1616,
1
1562, 1497, 1430, 1211, 1096, 827; H NMR (400 MHz, DMSO-d6): δ
10.64 (s, 1H, NH), 7.82–7.80 (m, 2H, ArH), 7.71 (d, J = 8.0 Hz, 2H, ArH),
7.47 –7.45 (m, 3H, ArH), 7.40 (d, J = 8.0 Hz, 2H, ArH); 13C NMR (100
MHz, DMSO-d6): δ 166.7, 163.6, 139.3, 132.9, 130.0, 129.0, 128.7, 127.4,
125.3, 118.9; MS (ESI) m/z (%): 334 (48), 336 ([M + H]+, 100), 338 (45);
HRMS-ESI calcd for C14H1135ClN380Se: (M + H)+: 335.9799; found:
335.9783.
Experimental
Infrared Spectra were determined on
a Nicolet Avatar-370
spectrophotometer in KBr. Melting points were measured on a Büchi
B-540 capillary melting point apparatus and are uncorrected. Mass
spectra (ESI-MS) were determined on a Thermo Finnigan LCQ-
Advantage instrument. High resolution mass spectra (ESI-HRMS)
were determined on an Agilent 6210 TOF instrument. 1H and 13C NMR
spectra were recorded on a Varian Mercury Plus-400 spectrometer
(400 and 100 MHz) using TMS as internal standard.
2-(4-Methylphenylamino)-5-phenyl-1,3,4-selenadiazole (5f): Yellow
crystals; yield 77%; m.p. 178.8–179.5 °C; IR (KBr) (nmax cm–1): 3450,
1
1613, 1566, 1515, 1433, 1259, 1206, 1096, 824; H NMR (400 MHz,
DMSO-d6): δ 10.42 (s, 1H, NH), 7.81–7.78 (m, 2H, ArH), 7.54 (d, J = 8.0
Hz, 2H, ArH), 7.48–7.45 (m, 3H, ArH), 7.15 (d, J = 8.0 Hz, 2H, ArH),
2.27 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6): δ 167.2, 162.3,
138.2, 133.0, 130.9, 129.7, 129.2, 128.9, 127.2, 117.5, 20.4; MS (ESI) m/z
(%): 314 (46), 316 ([M + H]+, 100); HRMS-ESI calcd for C15H14N380Se:
(M + H)+: 316.0348; found: 316.0333.
Synthesis of 2-amino-1,3,4-selenadiazoles 5a–p (5a was selected as
an example); general procedure
A mixture of phenyl isoselenocyanate (1a) (0.182 g, 1.0 mmol) and
hydrazine hydrate (0.063 g, 1.0 mmol) in CH2Cl2 (10 mL) was stirred
for about 0.5 h at room temperature until total consumption of the
starting material, monitored by TLC. Benzaldehyde (3a) (0.106 g,
1.0 mmol) and HOAc (0.066 g, 1.1 mmol) were added and the resulting
mixture was stirred at room temperature for 1 h to prepare phenyl
selenohydrazone (4a). Then NBS (0.267 g, 1.5 mmol) and NaOAc
(0.164 g, 2.0 mmol) were added directly to this mixture and the
whole was stirred at reflux for 2 h. After the reaction was complete,
the reaction mixture was filtered. The filtrate was washed with brine
(10 mL) and extracted with CH2Cl2 (2 × 10 mL). The combined
organic extracts were dried over Na2SO4 and concentrated under
vacuum. The residue was purified by column chromatography using
petroleum ether–EtOAc (6:1) (60–90 °C) as eluent to afford 5-phenyl-
2-phenylamino-1,3,4-selenadiazole (5a) as: Pink crystals, yield 0.230 g
(73%); m.p. 207.0–207.5 °C (lit.15 208–209 °C); IR (KBr) (nmax cm–1):
2-(4-Methoxyphenylamino)-5-phenyl-1,3,4-selenadiazole (5g): Yellow
crystals; yield 79%; m.p. 172.8–173.5 °C; IR (KBr) (nmax cm–1): 3449, 1624,
1562, 1497, 1415, 1247, 1176, 965, 835; 1H NMR (400 MHz, DMSO-d6): δ
10.33 (s, 1H, NH), 7.79–7.77 (m, 2H, ArH), 7.57 (d, J = 8.8 Hz, 2H, ArH),
7.45–7.43 (m, 3H, ArH), 6.94 (d, J = 8.8 Hz, 2H, ArH), 3.74 (s, 3H, ArH);
13C NMR (100 MHz, DMSO-d6): δ 166.9, 161.2, 160.1, 154.4, 134.3, 128.3,
125.7, 119.2, 114.1,114.0, 55.1; MS (ESI) m/z (%): 328 (48), 330 ([M – H]–,
100); HRMS-ESI calcd for C15H14N3O80Se: (M + H)+: 332.0297; found:
332.0286.
5-(2-Chlorophenyl)-2-(4-methylamino)-1,3,4-selenadiazole
(5h): Yellow solid; yield 64%; m.p. 213.1–214.5 °C; IR (KBr) (nmax
1
cm–1): 3443, 1610, 1564, 1424, 1292, 1108, 1032, 836, 750; H NMR
(400 MHz, DMSO-d6): δ 10.47 (s, 1H, NH), 8.10–8.08 (m, 1H, ArH),
7.64–7.61 (m, 1H, ArH), 7.56 (d, J = 8.0 Hz, 2H, ArH), 7.49–7.47 (m,
2H, ArH), 7.16 (d, J = 8.0 Hz, 2H, ArH), 2.27 (s, 3H, CH3); 13C NMR
(100 MHz, DMSO-d6): δ 169.5, 156.2, 138.1, 131.4, 131.1, 130.9, 130.5,
130.2, 129.8, 129.3, 127.5, 117.7, 20.5; MS (ESI) m/z (%): 348 (47), 350
([M + H]+, 100), 352 (42); HRMS-ESI calcd for C15H1335ClN380Se: (M +
H)+: 349.9956; found: 349.9943.
1
3446, 1614, 1565, 1495, 1450, 1246, 1107, 746; H NMR (400 MHz,
DMSO-d6): δ 10.54 (s, 1H, NH), 7.83–7.80 (m, 2H, ArH), 7.66 (d,
J = 8.0 Hz, 2H, ArH), 7.48–7.46 (m, 3H, ArH), 7.35 (t, J = 8.0 Hz, 2H,
ArH), 7.02 (t, J = 7.6 Hz, 1H, ArH); 13C NMR (100 MHz, DMSO-d6):
δ 167.1, 162.9, 140.6, 133.0, 129.8, 128.94, 128.88, 127.3, 122.0, 117.4;
ESI-MS m/z (%): 300 (51), 302 ([M + H]+,100); HRMS-ESI calcd for
C14H12N380Se: (M + H)+: 302.0191; found: 302.0193.
5-(4-Chlorophenyl)-2-(4-methylphenylamino)-1,3,4-selenadiazole
(5i): Yellow crystals; yield 71%; m.p. 203.3–204.5 °C; IR (KBr) (nmax
1
cm–1): 3444, 1614, 1572, 1518, 1431, 1206, 1109, 1094, 832; H NMR
(400 MHz, DMSO-d6): δ 10.43 (s, 1H, NH), 7.82 (d, J = 8.4 Hz, 2H,
ArH), 7.63 (d, J = 8.4 Hz, 2H, ArH), 7.52 (d, J = 8.4 Hz, 2H, ArH),
7.15 (d, J = 8.4 Hz, 2H, ArH), 2.27 (s, 3H, CH3); 13C NMR (100 MHz,
DMSO-d6): δ 167.6, 159.8, 134.2, 131.1, 129.3, 128.9, 128.8, 127.0,
117.6, 117.0, 20.4; MS (ESI) m/z (%): 348 (46), 350 ([M + H]+, 100),
352 (40); HRMS-ESI calcd for C15H1335ClN380Se: (M + H)+: 349.9956;
found: 349.9951.
5- (3-Methoxyphenyl) -2- (4-methylphenylamino) -1,3,4-
selenadiazole (5j): Yellow solid; yield 79%; m.p. 168.3–169.9 °C;
IR (KBr) (nmax cm–1): 3443, 1602, 1568, 1431, 1285, 1109, 772, 682;
1H NMR (400 MHz, CDCl3): δ 7.40 (t, J = 1.6 Hz, 1H), 7.33 (d, J =
8.4 Hz, 2H, ArH), 7.31–7.25 (m, 2H, ArH), 7.18 (d, J = 8.4 Hz, 2H,
ArH), 6.96–6.93 (m, 1H, ArH), 3.86 (s, 3H, OCH3), 2.35 (s, 3H, CH3);
13C NMR (100 MHz, CDCl3): δ 171.2, 161.5, 159.7, 139.0, 134.5, 133.8,
130.1, 129.8, 120.5, 119.0, 116.1, 111.8, 55.5, 21.0; MS (ESI) m/z (%):
344 (52), 346 ([M + H]+, 100); HRMS-ESI calcd for C16H16N3O80Se:
(M + H)+: 346.0454; found: 346.0442.
5- (4-Methoxyphenyl) -2- (4-methylphenylamino) -1,3,4-
selenadiazole (5k): Pink crystals; yield 80%; m.p. 198.7–199.5 °C; IR
(KBr) (nmax cm–1): 3444, 1612, 1568, 1518, 1430, 1249, 1174, 1034, 828;
1H NMR (400 MHz, DMSO-d6): δ 10.31 (s, 1H, NH), 7.72 (d, J = 8.4
Hz, 2H, ArH), 7.52 (d, J = 7.6 Hz, 2H, ArH), 7.14 (d, J = 7.6 Hz, 2H,
ArH), 7.01 (d, J = 8.4 Hz, 2H, ArH), 3.81 (s, 3H, OCH3), 2.26 (s, 3H,
CH3); 13C NMR (100 MHz, DMSO-d6): δ 166.5, 162.3, 160.3, 138.3,
130. 8, 129.3, 128.8, 125.7, 117.4, 114.4, 55.3, 20.5; MS (ESI) m/z (%):
5-(4-Chlorophenyl)-2-(phenylamino)-1,3,4-selenadiazole
(5b):
Yellow crystals; yield 71%; m.p. 209.6–212.0 °C (lit.15 213–214 °C);
IR (KBr) (nmax cm–1): 3442, 1620, 1601, 1502, 1451, 1418, 1089, 1013,
829, 744; 1H NMR (400 MHz, DMSO-d6): δ 10.54 (s, 1H, NH), 7.83 (d,
J = 8.8 Hz, 2H, ArH), 7.66 (d, J = 7.6 Hz, 2H, ArH), 7.53 (d, J = 8.8 Hz,
2H, ArH), 7.35 (t, J = 7.6 Hz, 2H ArH), 7.03 (t, J = 7.6 Hz, 1H, ArH);
13C NMR (100 MHz, DMSO-d6): δ 167.5, 140.5, 134.3, 131.9, 129.3,
129.0, 128.9, 128.8, 122.1, 117.5; ESI-MS m/z (%): 334 (40), 336 ([M
+ H]+,100), 338 (45); HRMS-ESI calcd for C14H1135ClN380Se: (M + H)+:
335.9799; found: 335.9800.
5-(4-Methylphenyl)-2-(phenylamino)-1,3,4-selenadiazole
(5c):
Yellow solid; yield 78%; m.p. 208.5–210.0 °C; IR (KBr) (nmax cm–1):
1
3241, 1601, 1573, 1453, 1423, 1214, 1093, 805, 744, 684; H NMR
(400 MHz, DMSO-d6): δ 10.48 (s, 1H, NH), 7.71–7.65 (m, 4H, ArH),
7.35 (t, J = 7.6 Hz, 2H, ArH), 7.28 (d, J = 8.0 Hz, 2H, ArH), 7.02 (t, J =
7.2 Hz, 1H, ArH), 2.35 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6):
δ 166.6, 140.6, 139.5, 131.4, 130.3, 129.3, 128.7, 127.1, 121.8, 117.4,
20.8; MS (ESI) m/z (%): 314 (45), 316 ([M + H]+, 100); HRMS-ESI
calcd for C15H14N380Se: (M + H)+: 316.0348; found: 316.0336.
5-(3-Methoxyphenyl)-2-(phenylamino)-1,3,4-selenadiazole (5d):
Yellow solid; yield 77%; m.p. 163.5–164.5 °C; IR (KBr) (nmax cm–1):
3450, 1599, 1571, 1506, 1421, 1273, 1181, 1077, 862, 746, 682; 1H NMR
(400 MHz, DMSO-d6): δ 7.45–7.38 (m, 5H, ArH), 7.34–7.26 (m, 2H,
ArH), 7.15 (t, J = 7.2 Hz, 1H, ArH), 6.98–6.95 (m, 1H, ArH), 3.87 (s,
3H, OCH3); 13C NMR (100 MHz, DMSO-d6): δ 170.5, 161.9, 159.7,

JOURNAL OF CHEMICAL RESEARCH 2016 181
344 (50), 346 ([M + H]+, 100); HRMS-ESI calcd for C16H16N3O80Se:
(M + H)+: 346.0454; found: 346.0445.
308 ([M + H]+, 100); HRMS-ESI calcd for C14H18N380Se: (M + H)+:
308.0661; found: 308.0662.
5-(4-Methylphenyl)-2-(4-methylphenylamino)-1,3,4-selenadiazole
(5l): Pink solid; yield 78%; m.p. 188.4–189.8 °C; IR (KBr) (nmax
We are grateful to the National Natural Science Foundation of
China (No. 21576239) and the Qianjiang Talent Project of the
Science Technology Department of Zhejiang Province (No.
2013R10059) for financial support.
1
cm–1): 3443, 1612, 1562, 1428, 1209, 1089, 805; H NMR (400 MHz,
DMSO-d6): δ 10.40 (s, 1H, NH), 7.68 (d, J = 7.2 Hz, 2H, ArH), 7.53 (d,
J = 6.4 Hz, 2H, ArH), 7.26 (d, J = 6.4 Hz, 2H, ArH), 7.14 (d, J = 7.2 Hz,
2H, ArH), 2.34 (s, 3H, OCH3), 2.27 (s, 3H, CH3); 13C NMR (100 MHz,
DMSO-d6): δ 166.6, 158.2, 139.6, 138.4, 130.8, 130.5, 129.5, 129.2,
127.2, 117.5, 21.0, 20.5; MS (ESI) m/z (%): 328 (55), 330 ([M + H]+,
100); HRMS-ESI calcd for C16H16N380Se: (M + H)+: 330.0504; found:
330.0493.
Electronic Supplementary Information
The HRMS data of 5p are available through:
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
2- (4-Methoxyphenylamino) -5- (4-methylphenyl) -1,3,4-
selenadiazole (5m): Yellow crystals; yield 81%; m.p. 158.7–159.8 °C;
IR (KBr) (nmax cm–1): 3443, 1616, 1573, 1513, 1434, 1320, 1251, 1091,
Received 6 November 2015; accepted 25 January 2016
Paper 1503699 doi: 10.3184/174751916X14558161990884
Published online: 24 February 2016
1
1038, 808; H NMR (400 MHz, DMSO-d6): δ 10.28 (s, 1H, NH),
7.66 (d, J = 8.4 Hz, 2H, ArH), 7.56 (d, J = 8.8 Hz, 2H, ArH), 7.26
(d, J = 8.4 Hz, 2H, ArH), 6.93 (d, J = 8.8 Hz, 2H, ArH), 3.74 (s, 3H,
OCH3), 2.34 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6): δ 167.3,
154.4, 139.5, 130.5, 129.5, 127.1, 125.2, 119.2, 118.3, 114.1, 55.2, 21.0;
MS (ESI) m/z (%): 344 (54), 346 ([M + H]+, 100); HRMS-ESI calcd
for C16H16N3O80Se: (M + H)+: 346.0454; found: 346.0441.
References
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5- (4-Methoxyphenyl) -2- (4-methoxyphenylamino) -1,3,4-
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830, 778; H NMR (400 MHz, DMSO-d6): δ 10.30 (br s, 1H, NH),
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(d, J = 8.8 Hz, 2H, ArH), 6.93 (d, J = 8.8 Hz, 2H, ArH), 3.81 (s, 3H,
OCH3), 3.74 (s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6): δ 167.6,
154.5, 134.3, 133.1, 129.7, 129.0, 127.3, 127.2, 119.3, 114.1, 55.3, 55.2;
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5- (4- Chlorophenyl) -2- (4-methoxyphenylamino) -1,3,4-
selenadiazole (5o): Yellow crystals; yield 74%; m.p. 203.3–204.5 °C
(lit.15 205–206 °C); IR (KBr) (nmax cm–1): 3444, 1614, 1572, 1518,
1431, 1206, 1109, 1094, 832; 1H NMR (400 MHz, DMSO-d6): δ 10.36
(s, 1H, NH), 7.81 (d, J = 8.4 Hz, 2H, ArH), 7.57 (d, J = 8.8 Hz, 2H,
ArH), 7.53 (d, J = 8.4 Hz, 2H, ArH), 6.94 (d, J = 8.8 Hz, 2H, ArH),
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134.0, 132.0, 128.9, 128.6, 127.9, 119.3, 118.5, 114.1, 55.2; MS (ESI)
m/z (%): 364 (50), 366 ([M + H]+, 100), 368 (51); HRMS-ESI calcd for
C15H13ClN3O80Se (M + H)+: 365.9905; found: 365.9907.
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2-Cyclohexylamino-5-phenyl-1,3,4-selenadiazole
(5p):
White
solid; yield 60%; m.p. 155.9–156.8 °C; IR (KBr) (nmax cm–1): 3163,
1564, 1437, 1363, 1261, 1055, 958, 889, 761, 688; 1H NMR (400 MHz,
DMSO-d6): δ 7.97 (d, J =7.2 Hz, 1H, ArH), 7.70–7.68 (m, 2H, ArH),
7.44–7.39 (m, 3H, 2ArH, NH), 3.65–3.57 (m, 1H, CH), 2.01–1.99 (m,
2H, CH2), 1.74–1.70 (m, 2H, CH2), 1.59–1.55 (m, 1H, CH2), 1.39–1.16
(m, 5H, CH2); 13C NMR (100 MHz, DMSO-d6): δ 170.3, 159.8, 133.4,
128.6, 128.3, 126.5, 54.2, 31.7, 24.9, 23.9; ESI-MS m/z (%): 306 (46),