Triselenium dicyanide (TSD) as a new cyanation reagent: Synthesis of cyano pterins and quinoxalines along with library of cyano N-heterocyclic compounds

Article abstract of DOI:10.1080/00397910802374141

Triselenium dicynide (TSD) has been reported for the first time to be a novel cyanation reagent for the microwave-assisted one-pot synthesis of a series of various types of cyano N-heterocycles such as pterin, deazapterin, quinoxaline, naphthyridine, and

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Triselenium Dicyanide (TSD)
as a New Cyanation Reagent:
Synthesis of Cyano Pterins
and Quinoxalines Along
with Library of Cyano N-
Heterocyclic Compounds
Shyamaprosad Goswami a , Annada C. Maity a ,
Nirmal K. Das a , Debabrata Sen a & Sibaprasad Maity
a
a Department of Chemistry, Bengal Engineering and
Science University, Shibpur, Howrah, India
Published online: 08 Jan 2009.
To cite this article: Shyamaprosad Goswami , Annada C. Maity , Nirmal K. Das ,
Debabrata Sen & Sibaprasad Maity (2009): Triselenium Dicyanide (TSD) as a New
Cyanation Reagent: Synthesis of Cyano Pterins and Quinoxalines Along with Library
of Cyano N-Heterocyclic Compounds, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:3, 407-415
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Synthetic Communications1, 39: 407–415, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802374141
Triselenium Dicyanide (TSD) as a New
Cyanation Reagent: Synthesis of Cyano Pterins
and Quinoxalines Along with Library of Cyano
N-Heterocyclic Compounds
Shyamaprosad Goswami, Annada C. Maity, Nirmal K. Das,
Debabrata Sen, and Sibaprasad Maity
Department of Chemistry, Bengal Engineering and Science University,
Shibpur, Howrah, India
Abstract: Triselenium dicynide (TSD) has been reported for the first time to be a
novel cyanation reagent for the microwave-assisted one-pot synthesis of a series
of various types of cyano N-heterocycles such as pterin, deazapterin, quinoxaline,
naphthyridine, and pyridine in good yields.
Keywords: Cyanation, heterocyclic compounds, microwave, selenium dioxide,
triselenium dicyanide
Heterocyclic molecules containing the cyano group are useful as drug
intermediates.[1–3] Thus, the development of new pathways leading to
efficient synthesis of heterocycles, with diversity in skeleton and func-
tional groups, is an important field of research in both synthetic and
medicinal chemistry.[4,5] Microwave-assisted[6] organic reactions such as
condensation,[7,8] addition, cross-coupling reaction, cyclo-addition, aro-
matic and benzylic substitution,[9] esterification, oxidation[10] or oxidative
degradations[11] and reduction reactions are well documented. However,
cyanation using triselenium dicyanide (TSD) remains unexplored. We
report herein, for the first time, TSD as a new cyanation reagent for
the synthesis of cyano heterocycles.
Received May 2, 2008.
Address correspondence to Shyamaprosad Goswami, Department of
Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711
103, India. E-mail: spgoswamical@yahoo.com
407

408
S. Goswami et al.
It is well known that halogen-substituted aryl compounds on
microwave-assisted Pd[12–14] and Cu-catalyzed[15] cyanation reactions give
aryl nitriles. The addition of TMSCN to a wide range of electron-rich
heteroaromatic compounds such as pyrroles, thiophenes, and indoles in
the presence of phenyliodine bis(trifluoroacetate) (PIFA) under mild
conditions produced the selective cyanation products.[16] Most of the
conventional cyanation reagents are moisture-sensitive. Previously rep-
orted reagents for this purpose are KCN or NaCN,[17] TMSCN,[18]
Zn(CN)2,[12,19–21] and K4[Fe(CN)6].[22–24] We have developed TSD as a
new and effective cyanation reagent for the synthesis of cyano hetero-
cycles by halogen substitution or by its direct incorporation in the
nucleus by hydrogen substitution (Scheme 1). However, direct cyanation
of aromatic or heterocyclic rings by direct hydrogen substitution is
unprecedented, and most of the reported methods focus on substitution
of halogens with cyano group. We were interested in a new development
in this regard.
TSD was first synthesized in 1925 by Birckenbach and Kellermann.
The X-ray structures[25] and the detailed spectral data[26] have also been
reported. Although the synthesis of aromatic and metallo-organic seleno-
cyanates was accomplished 40 years ago[27,28] by using TSD, cyanation
using this selenocyanating reagent has not been reported. Recently,
Kachanov reported[29] a convenient one-pot synthesis of TSD and the
selenocyanates of aromatic amines. The synthesis of 1,1,2,3,3-pentacya-
nopropene salts has been accomplished by the reaction of malononitrile
with SeO2 in the presence of organic bases.[30]
Mode of heating by microwave generally works with molecules hav-
ing polar functional groups. It was envisaged that the polar nature of the
SeꢀCN bond would help the reaction by microwave. Thus we have
speculated that TSD could be utilized not only as a selenocyanating
reagent but also as a cyanation reagent under appropriate conditions
and might lead to the formation of cyano heterocycles from different
types of heterocyclic compounds under microwave conditions. It is
expected that simple thermal heating would lead to cleavage of the weak-
est SeꢀSe bond. On the other hand, a more likely situation under micro-
wave heating may be that more polar SeꢀCN bond would absorb
Scheme 1. Facile method for the synthesis of cyano N-heterocyclic compounds.

Cyanation by Triselenium Dioxide
409
microwave energy more readily than the Se-Se bond that would induce its
cleavage in preference to the SeꢀSe bond. We have observed that the
microwave condition for this cyanation reaction using TSD is superior
than the thermal condition, and this cyanation reaction generally does
not occur thermally. The possible reason may be the fact that bond
strength and bond order in TSD for the SeꢀSe bond are much less[25]
than the Se-C bond in SeCN, and thus thermally selenocyanation is easier
than cyanation using TSD. However, only in the case of quinoxaline sys-
tem have we been able to isolate thermally cyano substituted quinoxaline.
The reaction conditions and yields are summarized in Table 1. The
method works very well for the rapid synthesis of a series of different
cyano substituted N-heterocycles, including cyano pterins and quinoxa-
lines. That cyano but not the selenocyano group was introduced in
the aromatic heterocycles under microwave conditions was confirmed
by spectral means, especially by mass spectral analysis. All the com-
pounds made here are well characterized by spectroscopic studies
(1H NMR, IR, and MS). Final confirmation of 4 is obtained by the
X-ray crystallographic investigation.[31]
In conclusion, we have developed an efficient, novel method for the
synthesis of a library of cyano N-heterocycles using TSD under micro-
wave conditions. In addition, this new cyanation method has the advan-
tages of short reaction time and simple reaction conditions. Most
important, we have also discovered that TSD also incorporates the cyano
group in heterocycles without the presence of any halogen group.
EXPERIMENTAL
Representative Procedure for the One-Pot Synthesis
of Cyano Heterocycles
A thoroughly ground mixture of selenium dioxide (1.32 g, 12 mmol) and
malononitrile (0.26 g, 4 mmol) in four to five drops of DMSO was kept
stirring in an open-mouth conical flask. The mixture became reddish-
brown after 7 min, while an exothermic reaction began during the next
10 min when TSD was formed.[29] The heterocyclic substrate quinoxaline
(0.39 g, 3 mmol) was added with stirring to the reaction mixture after ter-
mination of exothermic reaction. The conical flask was then placed in a
domestic microwave oven at 240 W for an optimum time of 20 min.
The progress of the reaction was monitored by thin-layer chromatogra-
phy (TLC). After completion of the reaction, water was added, and the
mixture was extracted with chloroform. The organic layer was washed
with saturated brine and dried over MgSO4, followed by evaporation

410
S. Goswami et al.
Table 1. Triselenium dicyanide (TSD)–mediated cyanation of various hetero-
cyclic compounds under microwave irradiation
Entry
1
Precursor
Conditiona,b
Product
Yieldc (%)
400 W, 15 min
56
2
3
240 W, 8 min
240 W, 7 min
62
67
4
5
6
7
400 W, 16 min
240 W, 20 min
400 W, 12 min
240 W, 18 min
72
74
68
62
4
8
9
240 W, 16 min
240 W, 15 min
45
43
10
400 W, 16 min
32
55
11
12
400 W, 10 min
400 W, 15 min
52
(Continued)

Cyanation by Triselenium Dioxide
411
Table 1. Continued
Entry
13
Precursor
Conditiona,b
400 W, 8 min
Product
Yieldc (%)
67
14
15
240 W, 9 min
240 W, 15 min
54
63
aReactions were monitored by TLC analysis.
bA domestic BPL-Sanyo microwave oven (800G) was used. All the reactions
were safe.
cYields refer to the isolated pure products after column chromatography.
with a rotary evaporator under low pressure, which afforded a white
crystalline solid. This was purified on silica gel (60–120 mesh) column
chromatography eluting with petroleum ether to give the compound 5
(0.34 g, 74%) as a crystalline solid.
Data
7-Cyano-6-methyl-2-pivaloylaminopteridin-4(3H)-one 1
ꢁ
1
Mp 116–118 C; H NMR (CDCl3, 300 MHz): d (ppm): 11.30 (br s, 1H,
NH), 8.70 (br s, 1H, NH), 3.33 (s, 3H), 2.61 (s, 3H).
6-Cyano-5-deazapterin 3
ꢁ
1
Mp 135–136 C; H NMR (CDCl3, 400 MHz): d (ppm): 11.72 (br s, 1H,
NH), 8.71 (d, 1H, J ¼ 1.77 Hz), 8.34 (d, 1H, J ¼ 1.77 Hz), 2.50 (s, 3H).
3-Methylquinoxaline-2-carbonitrile 4
ꢁ
1
Mp 146–147 C; H NMR (CDCl3, 300 MHz): d (ppm): 8.13 (m, 2H),
7.86 (m, 2H), 2.98 (s, 3H).

412
S. Goswami et al.
2-Quinoxalinecarbonitrile 5
ꢁ
1
Mp 117–118 C; H NMR (CDCl3, 300 MHz): d (ppm): 9.09 (s, 1H),
8.21–818 (m, 2H), 7.99–7.90 (m, 2H).
2-Quinolinecarbonitrile 6
ꢁ
Mp 85–86 C; 1H NMR (CDCl3, 400 MHz): d (ppm): 8.30 (d, 1H,
J ¼ 8.40 Hz), 8.17 (d, 1H, J ¼ 8.52 Hz), 7.89 (d, 1H, J ¼ 8.20 Hz), 7.84
(t, 1H, J ¼ 7.56 Hz), 7.70 (t, 1H, J ¼ 7.18 Hz).
2-Acetylamino-7-cyano-1,8-naphthyridine 7
ꢁ
1
Mp 144–146 C; H NMR (CDCl3, 300 MHz): d (ppm): 9.82 (br s, 1H,
NH), 7.76 (d, 1H, J ¼ 7.83 Hz), 7.68 (d, 1H, J ¼ 9.48 Hz), 7.05 (d, 1H,
J ¼ 7.83 Hz), 6.65 (d, 1H, J ¼ 9.45 Hz), 2.63 (s, 3H).
2-Amino-3-cyano-7-methyl-1,8-naphthyridine 8
1H NMR (CDCl3, 300 MHz): d (ppm): 7.92 (d, 1H, J ¼ 4.29 Hz), 7.52
(d, 1H, J ¼ 7.83 Hz), 6.89 (d, 1H, J ¼ 9.00 Hz), 4.46 (s, 3H), 3.32 (s, 3H).
2,9-Bis-methyl-7-cyano-[1,10] phenanthroline 9
Mp 122–124 ꢁC; 1H NMR (CDCl3, 300 MHz): d (ppm): 9.02 (s, 1H), 8.66
(d, 1H, J ¼ 8.19 Hz), 8.47 (d, 1H, J ¼ 6.60 Hz), 8.03 (d, 1H, J ¼ 6.54 Hz),
7.93 (d, 1H, J ¼ 8.61 Hz), 4.13 (s, 3H), 3.49 (3.49).
2-Amino-3-cyano pyridine 10
ꢁ
1
Mp 103–104 C; H NMR (CDCl3, 300 MHz): d (ppm): 8.36 (d, 1H,
J ¼ 4.23 Hz), 7.68 (t, 1H, J ¼ 7.65 Hz), 7.45 (br s, 2H, NH2), 6.98
(d, 1H, J ¼ 5.79 Hz).
3-cyano-2,6-diamino-pyridine 13
ꢁ
1
Mp 122–124 C; H NMR (CDCl3, 300 MHz): d (ppm): 7.48 (d, 1H,
J ¼ 8.04 Hz), 7.40 (d, 1H, J ¼ 8.04 Hz), 5.00 (br s, 2H, NH2), 4.31 (br s,
2H, NH2).

Cyanation by Triselenium Dioxide
ACKNOWLEDGMENTS
413
We thank DST [SR=S1=OC-13=2005], government of India, for financial
support. A. C. M. thanks the UGC, government of India, for the fellowship,
and we appreciate mass spectral help from Professor Thomas Schrader of
Duisburg-Essen University, Essen, Germany.
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