An Efficient Synthesis of Novel 1,3,5-Triazine-2-selenones from Acyl Isoselenocyanates and 2-Aminobenzimidazole

Full text of DOI:10.1080/00304948.2021.1872357

Organic Preparations and Procedures International
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An Efficient Synthesis of Novel 1,3,5-Triazine-2-
selenones from Acyl Isoselenocyanates and 2-
Aminobenzimidazole
Majid Ehsanfar, Mohammad H. Mosslemin & Alireza Hassanabadi
To cite this article: Majid Ehsanfar, Mohammad H. Mosslemin & Alireza Hassanabadi (2021):
An Efficient Synthesis of Novel 1,3,5-Triazine-2-selenones from Acyl Isoselenocyanates
and 2-Aminobenzimidazole, Organic Preparations and Procedures International, DOI:
10.1080/00304948.2021.1872357
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
https://doi.org/10.1080/00304948.2021.1872357
EXPERIMENTAL PAPER
An Efficient Synthesis of Novel 1,3,5-Triazine-2-selenones
from Acyl Isoselenocyanates and 2-Aminobenzimidazole
Majid Ehsanfara, Mohammad H. Mosslemina, and Alireza Hassanabadib
b
aDepartment of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran; Department of Chemistry,
Zahedan Branch, Islamic Azad University, Zahedan, Iran
ARTICLE HISTORY Received 3 December 2019; Accepted 30 September 2020
In recent years, increasing attention has been paid to organoselenium compounds
because of their diverse pharmaceutical and synthetic applications.1–11 For example, acyl
isoselenocyanates are useful reactive intermediates, and they have been prepared by the
reaction of acyl chlorides with KSeCN.12–14 The acyl isoselenocyanates, however, were
never isolated.15–18 The existence of these intermediates was inferred by their reactions
with nucleophiles.19–21 With this in mind, we now report on the use of such acyl isose-
lenocyanates, generated in situ, to prepare novel 1,3,5-triazine-2-selenones (Scheme 1,
compounds 4). The aim of our work was to prepare and rigorously characterize the
new 1,3,5-triazine-2-selenones via this unique synthetic route.
Initially, the reaction among benzoyl chloride, potassium selenocyanate, and 2-amino-
benzimidazole was selected as the model reaction for the preparation of compound 4a
(Ar ¼ Ph). A number of solvents were explored for this reaction. The results are sum-
marized in Table 1. Among the solvents tested, acetone was the best. When the reaction
was performed in dry acetone at room temperature for 8 h, 4-phenylbenzo[4,5]imi-
dazo[1,2-a][1,3,5]triazine-2-selenone (4a) was obtained in 80% yield. In light of this, we
used 1 mmol of acyl chloride, 1 mmol of potassium selenocyanate, and 1 mmol of 2-ami-
nobenzimidazole in dry acetone at room temperature for the rest of our reactions.
We thus examined a range of acyl chlorides containing different electron-donating
and electron-withdrawing groups. These were used to prepare acyl isoselenocyanates in
situ to afford the 4-substituted derivatives 4 (Table 2, mean yield 80%). There did not
seem to be much dependence of the reaction on the nature of substituents, as yields
were uniformly good.
CONTACT Majid Ehsanfar
ehsanfar_majid@yahoo.com
Department of Chemistry, Yazd Branch, Islamic Azad
University, Yazd, Iran
ß 2021 Taylor & Francis Group, LLC

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M. EHSANFAR ET AL.
Scheme 1. Synthesis of 1,3,5-triazine-2-selenones 4.
Table 1. The effect of solvents on the synthesis of 4a (R ¼ Ph).
Entry
Solvent
Time (h)
Yield (%)a
1
2
3
4
5
EtOH
Acetone
DMF
THF
MeCN
11
8
8
9
10
65
80
53
58
60
aIsolated yield.
Table 2. Yields of compounds 4a.
Entry
Ar
Product
Yield (%)b
1
2
3
4
5
6
7
8
C6H5
4-ClC6H4
4-BrC6H4
3-O2NC6H4
4-O2NC6H4
3,5-O2NC6H3
4-CH3C6H4
4-tBuC6H4
4a
4b
4c
4d
4e
4f
80
82
81
78
85
79
76
77
4g
4h
aReaction conditions: acyl chloride (2, 1 mmol) and KSeCN (3, 1 mmol) in acetone (6 mL) were stirred at r.t. 10 min and
then 2-aminobenzimidazole (1) in acetone (3 mL) was added. Stirring was continued at r.t. for 8 h.
bYields of isolated product.
The structures of compounds 4a-h were deduced from their elemental analysis and
1
their IR, H NMR, and 13C NMR spectra. The mass spectra of compounds 4a–h are all
fairly similar and display molecular ion peaks. For example, the mass spectrum of com-
pound 4a showed a molecular ion peak at 325, confirming that it is a (1:1:1) adduct.
The IR spectrum of compound 4a exhibited two absorption bands at 1674 cmꢀ1 for the
1
C ¼ N and 1259 cmꢀ1 for the C ¼ Se groups. The H NMR spectrum of compound 4a
exhibited aromatic protons as multiplets at 7.12-8.15 ppm. The 13C NMR spectrum of
compound 4a showed 13 distinct resonances in agreement with the proposed structure.
A plausible mechanism for the formation of selenones 4 is given in Scheme 2. The
reaction starts with the formation of acyl isoselenocyanate 5, followed by the addition
of 1 to afford intermediate 6. Subsequent cyclization of this intermediate generates 7,
which eliminates H2O to afford product 4.
In conclusion, trapping acyl isoselenicyanates, generated in situ from acyl chlorides
and potassium selenocyanate, by 2-aminobenzimidazole affords aryl-substituted ben-
zo[4,5]imidazo[1,2,a][1,3,5]triazine-2-selenone derivatives. The advantages of this

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
3
Scheme 2. Proposed mechanism for the synthesis of 1,3,5-triazine-2-selenones.
methodology are its operational simplicity, straightforward workup, substrate availabil-
ity, and potential diversity. Having explored a unique method for the synthesis of these
new compounds and their complete characterization, we hope that our preparative
experiments will stimulate further research into this novel category of heterocyc-
lic selenones.
Experimental section
Melting points were determined with an Electrothermal 9100 apparatus and are uncor-
rected. Elemental analyses were performed using a Heraeus CHN-O-Rapid analyzer.
Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating
at an ionization potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470
spectrometer. NMR spectra were obtained on a Brucker DRX 500 Avance spectrometer
(1H NMR at 500 MHz, 13C NMR at 125 MHz) in DMSO-d6 using TMS as an internal
standard. Chemical shifts (d) are given in parts per million (ppm). All of the chemicals
used in this study were purchased from Merck and Fluka (Buchs, Switzerland) and
were used without further purification.
Safety Notes: Caution! All workers must be thoroughly trained on the use of selen-
ium-containing compounds, and they must wear appropriate personal safety gear. All of
the reactions involving selenium-containing compounds must be carried out in a well-
ventilated hood.
General procedure for the synthesis of compounds 4
To a stirred solution of potassium selenocyanate (3, 0.144 g, 1 mmol) in dry acetone
(3 mL), a solution of acyl chloride (2, 1 mmol) in dry acetone (3 mL) was added at
room temperature. After 10 min, a solution of 2-aminobenzimidazole (1, 0.133 g,
1 mmol) in dry acetone (3 mL) was added to the mixture. After completion of the reac-
tion (ca. 8 h; as monitored by thin layer chromatography (silica gel; AcOEt/hexane 4/1))

4
M. EHSANFAR ET AL.
the precipitate which formed was filtered and washed with ether (10 mL) to give
the product.
4-Phenylbenzo[4,5]imidazo[1,2,a][1,3,5]triazine-2(10H)-selenone (4a)
Yellow solid. Yield 80%; mp 183-185 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3310, 1674, 1591, 1518,
1
1465, 1259 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 7.12 (t, 1H, J ¼ 8.1Hz),
7.28 (d, 1H, J ¼ 8.5Hz), 7.47 (t, 1H, J ¼ 8.8Hz), 7.52 (t, 2H, J ¼ 8.6Hz), 7.59 (t, 1H, J
¼ 8.5Hz), 7.95 (d, 1H, J ¼ 7.4Hz), 8.14 (d, 2H, J ¼ 7.3Hz), 12.63 (s, 1H, NH). 13C
NMR (125MHz, DMSO) d (ppm): d 111.3, 113.3, 122.0, 128.3, 128.4, 128.6, 129.2,
132.0, 132.4, 134.4, 152.0, 157.2 and 168.1 (C ¼ Se) ppm. ESI-MS (Mþ, 325).
Anal. Calcd. for C15H10N4Se: C, 55.40; H, 3.10; N, 17.23. Found: C, 55.71; H, 3.18;
N, 17.31.
4-(4-Chlorophenyl)benzo[4,5]imidazo[1,2-a][1,3,5]triazine-2(10H)-selenone (4b)
Yellow solid. Yield 82%; mp 197-199 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3320, 1670, 1583, 1511,
1
1456, 1258 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 7.15 (t, 1H, J ¼ 8.7Hz),
7.20 (d, 1H, J ¼ 8.6Hz), 7.44 (d, 1H, J ¼ 8.4Hz), 7.56 (t, 1H, J ¼ 8.3Hz), 7.93 (d, 2H, J
¼ 8.2Hz), 8.14 (d, 2H, J ¼ 8.4Hz), 12.53 (s, 1H, NH). 13C NMR (125MHz, DMSO) d
(ppm): d 111.1, 112.5, 122.6, 128.1, 128.5, 129.8, 130.0, 130.9, 137.5, 150.5, 152.8, 157.0
and 166.3 (C ¼ Se) ppm. ESI-MS (Mþ, 359).
Anal. Calcd. for C15H9ClN4Se: C, 50.09; H, 2.52; N, 15.58. Found: C, 50.11; H, 2.55;
N, 15.61.
4-(4-Bromophenyl)benzo[4,5]imidazo[1,2-a][1,3,5]triazine-2(10H)-selenone (4c)
Yellow solid. Yield 81%; mp 210-212 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3310, 1659, 1580, 1490,
1
1453, 1266 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 7.16 (t, 1H, J ¼ 8.4Hz),
7.21 (d, 1H, J ¼ 8.8Hz), 7.44 (d, 1H, J ¼ 8.2Hz), 7.71 (t, 1H, J ¼ 7.6Hz), 7.85 (d, 2H, J
¼ 8.1Hz), 8.07 (d, 2H, J ¼ 8.2Hz), 12.63 (s, 1H, NH). 13C NMR (125MHz, DMSO) d
(ppm): d 111.3, 112.7, 121.9, 125.5, 130.0, 130.5, 131.2, 131.7, 134.8, 150.2, 152.5, 156.0
and 166.6 (C ¼ Se) ppm. ESI-MS (Mþ, 404).
Anal. Calcd. for C15H9BrN4Se: C, 44.58; H, 2.24; N, 13.86. Found: C, 44.85; H, 2.31;
N, 13.98.
4-(3-Nitrophenyl)benzo[4,5]imidazo[1,2-a][1,3,5]triazine-2(10H)-selenone (4d)
Yellow solid. Yield 78%; mp 198-200 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3305, 1676, 1600, 1514,
1
1465, 1261 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 7.13 (t, 1H, J ¼ 7.3Hz),
7.20 (d, 1H, J ¼ 7.3Hz), 7.44 (d, 1H, J ¼ 7.4Hz), 7.72 (t, 1H, J ¼ 8.8Hz), 7.78 (t, 1H, J
¼ 8.8Hz), 8.32 (d, 1H, J ¼ 7.6Hz), 8.36 (d, 1H, J ¼ 7.3Hz), 8.68 (s, 1H, CH), 12.56
(s, 1H, NH). 13C NMR (125MHz, DMSO) d (ppm): d 111.0, 111.8, 121.8, 122.3, 123.3,
125.3, 129.6, 131.4, 134.4, 135.1, 137.2, 147.5, 152.6, 156.2 and 167.7 (C ¼ Se) ppm. ESI-
MS (Mþ, 370).

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
5
Anal. Calcd. for C15H9N5O2Se: C, 48.66; H, 2.45; N, 18.92. Found: C, 49.02; H, 2.60;
N, 18.98.
4-(4-Nitrophenyl)benzo[4,5]imidazo[1,2-a][1,3,5]triazine-2(10H)-selenone (4e)
Yellow solid. Yield 85%; mp 215-217 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3385, 1676, 1596, 1542,
1
1471, 1262 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 7.04 (t, 1H, J ¼ 8.1Hz),
7.24 (d, 1H, J ¼ 8.6Hz), 7.42 (d, 1H, J ¼ 8.9Hz), 7.67 (t, 1H, J ¼ 8.3Hz), 8.18 (d, 2H, J
¼ 7.3Hz), 8.24 (d, 2H, J ¼ 8.3Hz), 12.49 (s, 1H, NH). 13C NMR (125MHz, DMSO) d
(ppm): d 110.9, 111.0, 120.8, 122.9, 128.4, 129.4, 130.1, 133.7, 142.3, 148.6, 153.4, 156.1
and 168.4 (C ¼ Se) ppm. ESI-MS (Mþ, 370).
Anal. Calcd. for C15H9N5O2Se: C, 48.66; H, 2.45; N, 18.92. Found: C, 48.95; H, 2.50;
N, 18.96.
4-(3,5-Dinitrophenyl)benzo[4,5]imidazo[1,2-a][1,3,5]triazine-2(10H)-selenone (4f)
Yellow solid. Yield 79%; mp 220-222 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3300, 1686, 1600, 1532,
1
1454, 1259 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 7.12 (t, 1H, J ¼ 7.0Hz),
7.32 (d, 1H, J ¼ 7.0Hz), 8.01 (d, 1H, J ¼ 7.0Hz), 8.67 (t, 1H, J ¼ 7.9Hz), 8.85 (s, 1H,
CH), 8.96 (s, 2H, 2CH), 12.41 (s, 1H, NH). 13C NMR (125MHz, DMSO) d (ppm): d
111.0, 119.3, 120.6, 121.8, 127.5, 128.4, 131.3, 131.4, 141.7, 147.6, 152.6, 156.4, and 166.4
(C ¼ Se) ppm. ESI-MS (Mþ, 415).
Anal. Calcd. for C15H8N6O4Se: C, 43.39; H, 1.94; N, 20.24. Found: C, 44.03; H, 2.01;
N, 20.29.
4-(p-Tolyl)benzo[4,5]imidazo[1,2-a][1,3,5]triazine-2(10H)-selenone (4g)
Yellow solid. Yield 76%; mp 195-197 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3340, 1672, 1596, 1572,
1
1459, 1257 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 2.38 (s, 3H, CH3), 7.12
(t, 1H, J ¼ 8.6Hz), 7.28 (d, 1H, J ¼ 8.8Hz), 7.34 (d, 1H, J ¼ 8.0Hz), 7.46 (t, 1H, J ¼
8.6Hz), 7.82 (d, 2H, J ¼ 7.6Hz), 8.03 (d, 2H, J ¼ 7.8Hz), 12.32 (s, 1H, NH). 13C NMR
(125MHz, DMSO) d (ppm): d 20.9 (CH3), 111.1, 113.3, 122.7, 128.1, 128.7, 128.9, 129.1,
129.6, 142.8, 147.4, 150.4, 155.8 and 167.1 (C ¼ Se) ppm. ESI-MS (Mþ, 339).
Anal. Calcd. for C16H12N4Se: C, 56.65; H, 3.57; N, 16.51. Found: C, 56.70; H, 3.59;
N, 16.63.
4-(4-(tert-Butyl)phenyl)benzo[4,5]imidazo[1,2-a][1,3,5]triazine-2(10H)-
selenone (4h)
Yellow solid. Yield 77%; mp 193-195 ꢁC, IR (KBr) (ꢀmax cmꢀ1): 3345, 1661, 1623, 1566,
1
1451, 1258 cmꢀ1. H NMR (500MHz, DMSO-d6) d (ppm): d 1.32 (s, 9H, 3CH3), 7.12
(t, 1H, J ¼ 8.8Hz), 7.20 (d, 1H, J ¼ 8.8Hz), 7.35 (d, 1H, J ¼ 8.0Hz), 7.54 (t, 1H, J ¼
8.3Hz), 7.86 (d, 2H, J ¼ 8.2Hz), 8.07 (d, 2H, J ¼ 7.8Hz), 12.48 (s, 1H, NH). 13C NMR
(125MHz, DMSO) d (ppm): d 30.5 (3CH3), 34.4 (C), 110.9, 111.9, 121.0, 122.5, 124.8,

6
M. EHSANFAR ET AL.
124.9, 127.7, 128.8, 129.6, 150.2, 152.9, 155.8 and 166.9 (C ¼ Se) ppm. ESI-MS
(Mþ, 381).
Anal. Calcd. for C19H18N4Se: C, 59.84; H, 4.76; N, 14.69. Found: C, 59.90; H, 4.99;
N, 14.75.
Acknowledgments
Financial support by Yazd Branch, Islamic Azad University, is gratefully acknowledged.
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