A one-pot synthesis of 2H-pyrido[1,2-a][1,3,5]triazine-2-selenones from acyl isoselenocyanates and pyridin-2-amine

Article abstract of DOI:10.1007/s00706-016-1834-3

Abstract: Acyl isoselenocyanates, prepared by acyl chlorides and potassium selenocyanate, are trapped by pyridin-2-amine to afford 4-substituted pyrido[1,2-a][1,3,5]triazine-2-selenone in moderate to good yields. Graphical abstract: [Figure not available:

Full text of DOI:10.1007/s00706-016-1834-3

Monatsh Chem
DOI 10.1007/s00706-016-1834-3
ORIGINAL PAPER
A one-pot synthesis of 2H-pyrido[1,2-a][1,3,5]triazine-2-selenones
from acyl isoselenocyanates and pyridin-2-amine
Issa Yavari1 Shabnam Mosaferi1
•
Received: 17 May 2016 / Accepted: 4 August 2016
Ó Springer-Verlag Wien 2016
Abstract Acyl isoselenocyanates, prepared by acyl chlo-
rides and potassium selenocyanate, are trapped by pyridin-
2-amine to afford 4-substituted pyrido[1,2-a][1,3,5]tri-
azine-2-selenone in moderate to good yields.
Graphical abstract
acyl isoselenocyanates, which were generated by the
reaction of acyl chlorides and potassium selenocyanate, has
been described by Douglas [14].
Recently, a synthesis of aryl-substituted pyrido[1,2-
a][1,3,5]triazine-2-thione derivatives from acyl isothio-
cyanates was reported [15]. Herein, we describe a synthesis
of the seleno analog, namely pyrido[1,2-a][1,3,5]triazine-
2-selenone 3, from acyl isoselenocyanates, generated from
acyl chlorides and potassium selenocyanate, and pyridin-2-
amine in acetone. Both methods were one-pot reactions
performed at room temperature.
N
R
O
KSeCN
+
O
acetone
NH2
r.t., 8 h
Se
N
N
C
R
N
r.t., 10 min
N
Se
Cl
9 Examples
Yields: 60-85%
R
R = Alkyl, Aryl
Results and discussion
Keywords Pyridotriazineselenone Á
Acyl isoselenocyanate Á Acyl chlorides Á
Potassium selenocyanate
Initially, the reaction between benzoyl chloride, potassium
selenocyanate, and pyridin-2-amine was selected as the
model reaction. Various solvents such as MeCN, acetone,
N,N-dimethylformamide (DMF), tetrahydrofuran (THF),
and EtOH were explored. The results are summarized in
Table 1. Among these solvents, acetone was the best.
When the reaction was performed in dry acetone at room
temperature for 8 h, 4-phenyl-2H-pyrido[1,2-a][1,3,5]tri-
azine-2-selenone (3a) was obtained in 70 % yield
(Table 1). Thus, the optimized reaction conditions used
were 1 mmol of acyl chloride, 1 mmol of potassium
selenocyanate, and 1 mmol of pyridin-2-amine, in acetone
at room temperature.
Introduction
The current interest in selenium-containing organic com-
pounds stems from their remarkable synthetic and
biological functions [1–5]. Although the existence of
isoselenocyanates was doubted for a long time, the syn-
thesis of aryl and alkyl derivatives has been achieved in the
past decades [6]. Acyl isoselenocyanates are useful build-
ing blocks for the synthesis of linear and cyclic
selenoorganic compounds [7–13]. The first synthesis of
Using the optimized reaction conditions for the formation
of product 3a, a range of acyl chlorides containing different
electron-donating and electron-withdrawing groups were
treated with acyl isoselenocyanate to afford the 4-substi-
tuted-2H-pyrido[1,2-a][1,3,5]triazine-2-selenone deriva-
tives 3, in good yields (Table 2).
& Issa Yavari
yavarisa@modares.ac.ir
1
Department of Chemistry, Tarbiat Modares University,
PO Box 14115-175, Tehran, Iran
123

I. Yavari, S. Mosaferi
Table 1 Formation of product 3a under different reaction conditions
Entry
Solvent
Time/h
Yield/%
1
2
3
4
5
MeCN
Acetone
DMF
10
8
62
70
51
60
54
8
THF
11
11
EtOH
Table 2 Formation of pyrido[1,2-a][1,3,5]triazine-2-selenones 3
Entry
R
Product
Yield/%
1
2
3
4
5
6
7
8
9
Ph
3a
3b
3c
3d
3e
3f
70
68
69
81
78
85
60
63
64
2-Tol
4-Tol
2-Cl-C6H4
3-Cl-C6H4
4-Cl-C6H4
Me
3g
3h
3i
Et
t-Bu
Structures of compounds 3a–3i were assigned by IR, 1H
and 13C NMR, and MS data. The 1H NMR spectrum of 3a
exhibited characteristic multiplets for the aromatic
H-atoms. The selenone 13C resonances of compounds 3
were observed at 190–193 ppm. The MS spectrum of 3a
displayed the molecular-ion peak at m/z = 287. The NMR
spectra of compounds 3b–3i are similar to those of 3a,
except for the substituents, which showed characteristic
signals in the appropriate regions of the spectra.
of acyl isoselenocyanate 4, followed by the addition of 2 to
afford intermediate 5. Subsequent cyclization of this
intermediate generates 6, which eliminates H2O to afford
product 3.
In conclusion, trapping acyl isoselenocyanates, gener-
ated from acyl chlorides and potassium selenocyanate, by
pyridin-2-amine affords aryl(alkyl)-substituted pyrido[1,2-
a][1,3,5]triazine-2-selenone derivatives. The advan-
tages of this methodology are its operational simplicity,
simple workup, substrate availability, and potential
diversity.
A plausible mechanism for the formation of selones 3 is
given in Scheme 1. The reaction starts with the formation
123

A one-pot synthesis of 2H-pyrido[1,2-a][1,3,5]triazine-2-selenones from acyl…
Scheme 1
(C=N), 192.8 (C=Se) ppm; EI–MS: m/z = 287 (M?, 7),
Experimental
209 (15), 194 (30), 183 (100), 103 (24), 92 (11), 77 (90).
All of the chemicals used in this study were purchased
from Merck and were used without further purification.
Melting points were measured on an Electrothermal 9100
apparatus. Elemental analyses for C and H were performed
using a Heraeus CHN-O-Rapid analyzer. The experimental
data were in good agreement with the calculated values. IR
Spectra: Shimadzu-IR-460 spectrometer; bond positions in
cm-1. 1H and 13C NMR spectra: Bruker DRX-500 Avance
instrument at 500.1 and 125.7 MHz, respectively; d in
ppm, J in Hz. MS: Finnigan-MAT-8430EI-MS mass
spectrometer; at 70 eV; in m/z (rel. %). Chromatography
columns were prepared from Aldrich silica gel 70-230
mesh.
4-(o-Tolyl)-2H-pyrido[1,2-a][1,3,5]triazine-2-selenone
(3b, C14H11N3Se)
Yellow solid; m.p.: 125–127 °C; yield: 0.20 g (68 %); IR
-1
ꢀ
(KBr): m = 1683, 1583, 1433, 1273 (C=Se) cm
;
1H
NMR (CDCl3): d = 2.42 (3H, s, Me), 7.09 (1H, d,
3J = 7.6 Hz, Ar), 7.11 (1H, t, 3J = 7.8 Hz, Ar), 7.22
3
(1H, t, J = 7.6 Hz, Ar), 7.30 (1H, d, J = 7.8 Hz, Ar),
3
3
3
7.34 (1H, t, J = 7.8 Hz, Ar), 7.42 (1H, t, J = 7.6 Hz,
Ar), 8.18 (1H, d, 3J = 7.6 Hz, Ar), 8.57 (1H, d,
3J = 7.8 Hz, Ar) ppm; 13C NMR (CDCl3): d = 20.3
(Me), 119.5 (CH), 122.5 (CH), 125.4 (CH), 126.3 (CH),
127.9 (CH), 131.0 (CH), 131.2 (CH), 131.8 (CH), 135.5
(C), 138.4 (C), 153.2 (C=N), 173.0 (C=N), 191.5 (C=Se)
ppm; EI–MS: m/z = 301 (M?, 2), 209 (12), 208 (10), 183
(15), 117 (97), 92 (100), 91 (85).
Caution! All of the reactions involving selenium-con-
taining compounds should be carried out in a well-
ventilated hood.
4-(p-Tolyl)-2H-pyrido[1,2-a][1,3,5]triazine-2-selenone
(3c, C14H11N3Se)
General procedure for preparation of compounds 3
Yellow solid; m.p.: 134–136 °C; yield: 0.21 g (69 %); IR
-1
(KBr): m = 1693, 1608, 1428, 1269 (C=Se) cm
;
1H
ꢀ
To
a solution of 0.144 g potassium selenocyanate
(1 mmol) in 2 cm3 dry acetone was added acyl chloride
1a–1i (1 mmol) in 2 cm3 dry acetone. The reaction mixture
was stirred at r.t. for 10 min. Pyridin-2-amine (2, 0.094 g,
1 mmol) in 2 cm3 dry acetone was added to the mixture
and after completion of the reaction [ca. 8 h; TLC (AcOEt/
hexane 1:5) monitoring], extracted with CH2Cl2, and
washed with water. The organic layer was dried over
Na2SO4 and evaporated to dryness. The residue was puri-
fied by flash column chromatography [SiO2 (230–400
mesh; Merck); AcOEt/hexane 1:5] to give the products.
NMR (CDCl3): d = 2.40 (3H, s, Me), 7.25 (1H, t,
3J = 6.9 Hz, Ar), 7.27 (2H, d, 3J = 7.9 Hz, Ar), 7.73
3
3
(1H, d, J = 6.9 Hz, Ar), 7.89 (1H, t, J = 6.9 Hz, Ar),
3
3
8.22 (2H, d, J = 7.9 Hz, Ar), 8.55 (1H, d, J = 6.9 Hz,
Ar) ppm; 13C NMR (CDCl3): d = 22.0 (Me), 119.8 (CH),
121.7 (CH), 128.5 (C), 129.7 (2 CH), 130.2 (2 CH), 135.6
(C), 138.6 (CH), 139.8 (CH), 155.7 (C=N), 179.3 (C=N),
191.1 (C=Se) ppm; EI–MS: m/z = 301 (M?, 9), 209 (19),
208 (11), 183 (4), 117 (100), 92 (15), 91 (78).
4-(2-Chlorophenyl)-2H-pyrido[1,2-a][1,3,5]triazine-2-se-
lenone (3d, C13H8ClN3Se)
4-Phenyl-2H-pyrido[1,2-a][1,3,5]triazine-2-selenone (3a,
C13H9N3Se)
Yellow solid; m.p.: 143–145 °C; yield: 0.26 g (81 %); IR
-1
ꢀ
(KBr): m = 1708, 1588, 1435, 1274 (C=Se) cm
;
1H
Yellow solid; m.p.: 120–122 °C; yield: 0.20 g (70 %); IR
3
-1
;
1H
NMR (CDCl3): d = 7.21 (1H, t, J = 7.4 Hz, Ar), 7.22
(1H, t, J = 7.4 Hz, Ar), 7.25 (1H, d, J = 8.0 Hz, Ar),
ꢀ
(KBr): m = 1700, 1552, 1429, 1265 (C=Se) cm
3
3
3
NMR (CDCl3): d = 7.27 (1H, t, J = 6.7 Hz, Ar), 7.47
(2H, t, J = 7.6 Hz, Ar), 7.58 (1H, t, J = 7.6 Hz, Ar),
3
3
3
3
7.27 (1H, t, J = 8.0 Hz, Ar), 7.29 (1H, t, J = 8.0 Hz,
Ar), 7.48 (1H, d, 3J = 8.0 Hz, Ar), 7.67 (1H, d,
3J = 7.4 Hz, Ar), 8.46 (1H, d, 3J = 7.4 Hz, Ar) ppm;
13C NMR (CDCl3): d = 122.6 (CH), 126.0 (CH), 127.3
(CH), 128.9 (CH), 129.3 (CH), 130.2 (CH), 130.9 (CH),
131.3 (C), 132.1 (CH), 135.1 (C), 151.6 (C=N), 169.2
3
3
7.78 (1H, d, J = 6.7 Hz, Ar), 7.91 (1H, t, J = 6.7 Hz,
Ar), 8.32 (2H, d, 3J = 7.6 Hz, Ar), 8.56 (1H, d,
3J = 6.7 Hz, Ar) ppm; 13C NMR (CDCl3): d = 120.2
(CH), 121.1 (CH), 129.1 (2 CH), 129.8 (2 CH), 133.0 (CH),
138.0 (C), 138.9 (CH), 140.0 (CH), 154.5 (C=N), 179.4
123

I. Yavari, S. Mosaferi
(C=N), 190.1 (C=Se) ppm; EI–MS: m/z = 321 (M?, 6),
Pale-yellow solid; m.p.: 66–68 °C; yield: 0.15 g (63 %);
1
IR (KBr): m = 1697, 1582, 1433, 1276 (C=Se) cm-1; H
ꢀ
228 (10), 209 (15), 183 (25), 137 (100), 111 (42), 92 (24).
3
NMR (CDCl3): d = 1.25 (3H, t, J = 7.5 Hz, Me), 2.47
(2H, q, J = 7.5 Hz, CH2), 7.28 (1H, d, J = 6.6 Hz, Ar),
4-(3-Chlorophenyl)-2H-pyrido[1,2-a][1,3,5]triazine-2-se-
lenone (3e, C13H8ClN3Se)
3
3
3
3
7.47 (1H, t, J = 6.6 Hz, Ar), 7.84 (1H, t, J = 6.6 Hz,
Ar), 8.49 (1H, d, 3J = 6.6 Hz, Ar) ppm; 13C NMR
(CDCl3): d = 11.5 (CH2), 26.3 (Me), 119.1 (CH), 120.9
(CH), 138.5 (CH), 140.3 (CH), 152.0 (C=N), 171.9 (C=N),
191.3 (C=Se) ppm; EI–MS: m/z = 239 (M?, 4), 209 (9),
183 (11), 146 (100), 92 (42), 55 (21), 29 (40).
Yellow solid; m.p.: 141–143 °C; yield: 0.25 g (78 %); IR
-1
ꢀ
(KBr): m = 1675, 1600, 1425, 1275 (C=Se) cm
;
1H
3
NMR (CDCl3): d = 7.29 (1H, t, J = 6.8 Hz, Ar), 7.40
(1H, d, J = 7.7 Hz, Ar), 7.43 (1H, t, J = 7.7 Hz, Ar),
3
7.76 (1H, d, J = 6.8 Hz, Ar), 7.93 (1H, t, J = 6.8 Hz,
3
3
3
3
Ar), 8.01 (1H, d, J = 7.7 Hz, Ar), 8.11 (1H, s, Ar), 8.58
(1H, d, 3J = 6.8 Hz, Ar) ppm; 13C NMR (CDCl3):
d = 120.5 (CH), 122.4 (CH), 128.3 (CH), 130.2 (CH),
130.5 (CH), 130.7 (CH), 132.7 (CH), 135.1 (C), 135.5 (C),
139.9 (CH), 156.2 (C=N), 179.5 (C=N), 190.2 (C=Se) ppm;
EI–MS: m/z = 321 (M?, 6), 228 (10), 209 (14), 183 (18),
137 (100), 111 (72), 92 (28).
4-(tert-Butyl)-2H-pyrido[1,2-a][1,3,5]triazine-2-selenone
(3i, C11H13N3Se)
Pale-yellow solid; m.p.: 67–69 °C; yield: 0.17 g (64 %);
1
IR (KBr): m = 1689, 1581, 1434, 1274 (C=Se) cm-1; H
ꢀ
NMR (CDCl3): d = 1.01 (9H, s, Me3C), 7.18 (1H, d,
3
3J = 6.6 Hz, Ar), 7.46 (1H, t, J = 6.6 Hz, Ar), 7.83 (1H,
3
3
t, J = 6.6 Hz, Ar), 8.61 (1H, d, J = 6.6 Hz, Ar) ppm;
13C NMR (CDCl3): d = 22.9 (Me3C), 47.0 (C), 118.9
(CH), 120.2 (CH), 138.9 (CH), 140.1 (CH), 151.2 (C=N),
171.7 (C=N), 190.3 (C=Se) ppm; EI–MS: m/z = 267 (M?,
4), 209 (6), 183 (20), 174 (32), 92 (22), 83 (63), 57 (100).
4-(4-Chlorophenyl)-2H-pyrido[1,2-a][1,3,5]triazine-2-se-
lenone (3f, C13H8ClN3Se)
Yellow solid; m.p.: 147–149 °C; yield: 0.27 g (85 %); IR
-1
ꢀ
(KBr): m = 1640, 1576, 1428, 1267 (C=Se) cm
;
1H
3
NMR (CDCl3): d = 7.32 (1H, t, J = 6.9 Hz, Ar), 7.46
(2H, d, J = 7.3 Hz, Ar), 7.54 (1H, d, J = 6.9 Hz, Ar),
3
3
3
3
7.94 (1H, t, J = 6.9 Hz, Ar), 8.04 (2H, d, J = 7.3 Hz,
Ar), 8.58 (1H, d, 3J = 6.9 Hz, Ar) ppm; 13C NMR
(CDCl3): d = 118.9 (CH), 121.5 (CH), 128.7 (C), 130.0
(2 CH), 130.8 (2 CH), 136.6 (C), 138.9 (CH), 140.3 (CH),
155.2 (C=N), 179.2 (C=N), 191.4 (C=Se) ppm; EI–MS: m/
z = 321 (M?, 3), 228 (14), 209 (8), 183 (11), 137 (100),
111 (43), 92 (17).
References
1. Wirth T (ed) (2012) Organoselenium chemistry: synthesis and
reactions. Wiley-VCH, Weinheim
2. Sydnes MO, Isobe M (2015) Monatsh Chem 146:351
3. Razus AC, Birzan L, Hanganu A, Cristea M, Ungureanu E-M,
Soare M-L, Buica G-O (2014) Monatsh Chem 145:1999
ˇ
´ ´ ˇ ´
4. Rvovic MD, Divac VM, Jankovic NZ, Bugarcic ZM (2013)
Monatsh Chem 144:1227
4-Methyl-2H-pyrido[1,2-a][1,3,5]triazine-2-selenone (3g,
C8H7N3Se)
´
´
´
ˇ ´
ˇ
´
´
ˇ ´
5. Filipovic N, Polovic N, Raskovic B, Misirlic-Dencic S, Dulovic
M, Savic M, Niksic M, Mitic D, Andelkovic K, Todorovic T
´
´
´
´
¯
(2014) Monatsh Chem 145:1089
Pale-yellow solid; m.p.: 59–61 °C; yield: 0.13 g (60 %);
6. Banert K, Toth C (1995) Angew Chem Int Ed 34:1627
7. Garud DR, Koketsu M, Ishihara H (2007) Molecules 12:504
8. Heimgartner H, Zhou Y, Atanassov PK, Sommen GL (2008)
Phosphorus Sulfur Silicon, and Relat. Elem 183:840
9. Ninomiya M, Garud DR, Koketsu M (2010) Heterocycles
81:2027
1
IR (KBr): m = 1714, 1588, 1434, 1280 (C=Se) cm-1; H
ꢀ
NMR (CDCl3): d = 2.30 (3H, s, Me), 7.26 (1H, d,
3J = 6.5 Hz, Ar), 7.39 (1H, t, 3J = 6.5 Hz, Ar), 7.87
3
3
(1H, t, J = 6.5 Hz, Ar), 8.62 (1H, d, J = 6.5 Hz, Ar)
ppm; 13C NMR (CDCl3): d = 24.5 (Me), 118.2 (CH),
120.8 (CH), 137.9 (CH), 139.7 (CH), 151.9 (C=N), 171.5
(C=N), 190.6 (C=Se) ppm; EI–MS: m/z = 225 (M?, 2),
209 (7), 183 (20), 132 (31), 92 (100), 41 (51), 15 (20).
10. Koketsu M, Yamamura Y, Ishihara H (2006) Heterocycles
68:1191
11. Koketsu M, Yamamura Y, Ishihara H (2006) Synthesis 16:2738
12. Mohr F (2014) J Heterocycl Chem 51:1435
13. Yavari I, Mosaferi S (2016) Helv Chim Acta 99:130
14. Douglas IB (1937) J Am Chem Soc 59:740
15. Mohebat R, Saeedi F (2012) J Sulfur Chem 33:583
4-Ethyl-2H-pyrido[1,2-a][1,3,5]triazine-2-selenone (3h,
C9H9N3Se)
123