One-pot synthesis of 1-substituted-5-alkylselanyl-1H-tetrazoles from isoselenocyanates: Unexpected formation of N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas

Article abstract of DOI:10.1016/j.tet.2013.07.103

1-Substituted-5-alkylsulfanyl-1H-tetrazoles are well known class of organic substances with various applications in medicinal chemistry or photographic industry. Their selenium analogues, 1-substituted-5-alkylselanyl-1H-tetrazoles are, however, much less explored because of the lack of suitable methods for their preparation. In this work we investigated the synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles from synthetically available alkyl/arylisoselenocyanates. One-pot reactions of arylisoselenocyanates with sodium azide and alkylating agent led to the target 5-alkylselanyl-1-aryl-1H- tetrazoles but also to interesting side products, namely N-alkyl-N- arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas. Nevertheless, when alkylisoselenocyanates were utilized as the substrates, the reactions led exclusively to the formation of 1-alkyl-5-alkylselanyl-1H- tetrazoles in good yields. This simple one-pot procedure brings new possibilities for the preparation of variously substituted selenium compounds. It also opens the way to further investigations of selenium isosteres of the widely utilized 5-thiotetrazole moiety in biomedical applications.

Full text of DOI:10.1016/j.tet.2013.07.103

Tetrahedron 69 (2013) 8798e8808
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot synthesis of 1-substituted-5-alkylselanyl-1H-tetrazoles
from isoselenocyanates: unexpected formation of N-alkyl-N-
arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N0-diarylisoselenoureas
,
a
Galina Karabanovich a, Jaroslav Roh a , Zdenka Padelkova , Zdenek Novak ,
ꢁ b
ꢀ
ꢁ
*
ꢀ
ꢀ
a
ꢀ
ꢁ
ꢁ a
ꢁ
Katerina Vavrova , Alexandr Hrabalek
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203,
a
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
Hradec Kralove 50005, Czech Republic
b
ꢁ
Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10,
Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 April 2013
Received in revised form 11 July 2013
Accepted 22 July 2013
Available online 4 August 2013
1-Substituted-5-alkylsulfanyl-1H-tetrazoles are well known class of organic substances with various
applications in medicinal chemistry or photographic industry. Their selenium analogues, 1-substituted-
5-alkylselanyl-1H-tetrazoles are, however, much less explored because of the lack of suitable methods
for their preparation. In this work we investigated the synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tet-
razoles from synthetically available alkyl/arylisoselenocyanates. One-pot reactions of arylisoseleno
cyanates with sodium azide and alkylating agent led to the target 5-alkylselanyl-1-aryl-1H-tetrazoles but
also to interesting side products, namely N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N0-dia-
rylisoselenoureas. Nevertheless, when alkylisoselenocyanates were utilized as the substrates, the re-
actions led exclusively to the formation of 1-alkyl-5-alkylselanyl-1H-tetrazoles in good yields. This
simple one-pot procedure brings new possibilities for the preparation of variously substituted selenium
compounds. It also opens the way to further investigations of selenium isosteres of the widely utilized 5-
thiotetrazole moiety in biomedical applications.
Keywords:
Selenium
Isoselenocyanate
Tetrazole
Cyanamide
Tetrazole-5-selenol
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Our group has been interested in the chemistry of tetrazole-
containing compounds, especially 5-substituted tetrazoles and
Selenium is a trace element, essential for normal human de-
velopment, growth, metabolism, and function of the immune sys-
tem. Originally, selenium was considered as one of the most toxic
elements. Its benefits were not fully appreciated until 1957, when
Schwarz and Foltz described the relationship between selenium
intake by food and prevention of liver necrosis in rats.1 In 1973 it
was discovered that selenium is a part of glutathione peroxidases
GSHPx, antioxidant proteins that reduce potentially damaging re-
active oxygen species, such as hydrogen peroxide and lipid hy-
droperoxides, to harmless products.2 In recent years increasing
attention has been paid to selenium-containing compounds due to
their use as synthetic tools,3 and as promising biologically active
substances exhibiting antifungal,4 antimycobacterial,5 antiviral,6
antitumor7 or antihypertensive properties.8
substituted tetrazole-5-thiols. Tetrazoles are a well-described class
of nitrogen-containing heterocycles with valuable properties,
which have found widespread application in various fields of in-
dustry and science, mainly in medicinal chemistry as lipophilic and
metabolically stable surrogates for other functional groups.9,10
Tetrazole-5-thiols are also a frequent fragment of pharmaceuti-
cally active compounds. The best-known examples of drug con-
taining 1-substituted-5-alkyl/arylsulfanyl-1H-tetrazole are the
b-
lactam antibiotics of the cephalosporin and cephamycin series,
which exhibit low toxicity and a wide spectrum of antibacterial
activity.10 In addition, 1-aryltetrazol-5-ylthioacetanilides were
identified as potent inhibitors of HIV-1RT with low nanomolar in-
trinsic activity on the enzyme and submicromolar antiviral activity
in HIV infected cells.11 In a series of 1-substituted 5-alkyl/arylsul-
fanyl-1H-tetrazole compounds, antitubercular,12,13 antibacterial,14
and antifungal activities15 were found.
Although the chemistry of selenium compounds is quite similar
to the chemistry of sulfur compounds, 1-substituted-5-alkyl/aryl-
selanyl-1H-tetrazoles have been much less explored compared to
* Corresponding author. Tel.: þ420 495067339; fax: þ420 495067166; e-mail
addresses: jaroslav.roh@faf.cuni.cz, roh_j1aa@faf.cuni.cz (J. Roh).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.103

G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
8799
their sulfur isosteres. Most publications dealing with 5-selanyl
tetrazoles describe the syntheses of 5-alkyl/arylselanyl-1H-tetra-
zoles (1) based on the reaction of alkyl/arylselenocyanates with
sodium azide under various conditions (Scheme 1).16e18 5-Alkyl/
arylselanyl-1H-tetrazoles could be subsequently functionalized.
However, low regioselectivity of these reactions leads to the for-
mation of 1,5- and mainly 2,5-disubstituted derivatives.9,19 A series
of compounds 2 (Fig. 1), which have been synthesized from corre-
sponding 5-arylselanyl-1H-tetrazoles and p-toluensulfonic acid
using dicyclohexylcarbodiimide, can be shown as an example.20
However, the resulting 1,5-regioisomer was not fully confirmed.
alkyl/arylisothiocyanates. This involved both two-step and one-pot
procedures under various conditions including phase-transfer
catalysis.
2. Results and discussion
The starting alkyl/arylisoselenocyanates 10e16 were prepared
by a one-pot reaction from the corresponding N-alkyl/arylfor-
mamides 9 (Table 1).29 The reaction proceeded through the for-
mation of an isonitrile, which than reacted with selenium to form
an isoselenocyanate. These compounds are an advantageous
starting material for the synthesis of different organoselenium
compounds because of their simple synthesis and safety handling
and storage.
H
N
N
NaN3, Et3N.HCl
PhMe, reflux
KSeCN
N
N
R X
X = I, Br, N2+Cl-
1. Synthesis of
R Se C N
R Se
1
Table 1
Preparation of alkyl/arylisoselenocyanates 10e16.
Scheme
5-alkyl/arylselanyl-1H-tetrazoles
from
alkyl/
1) Et3N, triphosgene
arylselenocyanates.
O
H
2) Se powder
H
N
R1
R1 NCSe
CH2Cl2, reflux
9
10-16
O
R
R1
Yield [%]
N N
N N
N N
N
Entry
Product
N
O
N
N
Se
Se
Se
N
Ph
1
2
3
4
5
6
7
10
11
12
13
14
15
16
Phe
4-MeOPhe
4-BrPhe
CH3(CH2)3e
CH3(CH2)5e
C6H11e
63
68
58
67
43
98
67
N
Ph
N
O
N
H
Ts
2
3
4
H
N
Y
CH3(CH2)7e
R1
N N
N N
N
O
N
Se
Se
N
Ar
N
Ph
HN
R
First, we attempted to synthesize 1-substituted-1H-tetrazole-5-
selenols from the corresponding isoselenocyanates. To find suitable
conditions for the preparation of 1-substituted-1H-tetrazole-5-
selenols, we treated phenylisoselenocyanate (10) with sodium
azide in various solvents (H2O, CH3OH, C2H5OH, CH3CN, THF, DMF,
CH3NO2, Et3N, CH2Cl2/H2O), with tetrabutylammonium azide
(TBAA) or Et3N$HN3 in toluene or CH2Cl2, with Me3SnN3 in toluene,
THF, CH3CN or CH2Cl2 and also with Me3SiN3 itself. Unfortunately
all these reactions led to decomposition with precipitation of se-
lenium powder, confirming that many nucleophilic selenium spe-
cies are highly reactive and usually cannot be isolated.30 Neverthe
less, reaction of cyclohexylisoselenocyanate (15) with sodium azide
in water was successful and sodium 1-cyclohexyl-1H-tetrazole-5-
selenolate was isolated as a mixture with residual sodium azide.
Unfortunately, acidification of sodium 1-cyclohexyl-1H-tetrazole-
5-selenolate led to precipitation of red selenium at pH 5.5e6.
As tetrazole-5-selenolates were sensitive to acidification, we
decided to alkylate them without isolation under the conditions of
phase-transfer catalysis with tetrabutylammonium bromide
(TBAB) as a phase-transfer catalyst (method 1, Table 2). Reaction of
alkylisoselenocyanates 13e15 with sodium azide followed by ad-
dition of an alkylating agent under the condition of phase-transfer
catalysis led to the formation of the intended 1-alkyl-5-alkyl
selanyl-1H-tetrazoles (23a, 25a, 26a, 31a, 33a, and 34a) as the
only products, but only in low-to-moderate yields (11e50%). In the
case of aryl derivatives, the target compounds (17e19a, 21a) were
formed in very low yields (5e14%), due to an unexpected formation
of N-alkyl-N-arylcyanamides (17e19b) as the main products.
Moreover, reaction of 4-bromophenylisoselenocyanate (12) led to
complex mixture of products. In the case of alkyl derivatives, the
formation of N,N-disubstituted cyanamides was not observed.
These results encouraged us to carry out one-pot reactions in an
attempt to immediately alkylate tetrazole-5-selenolate before its
decomposition. Reactions of phenylisoselenocyanate (10) and 4-
methoxyphenylisoselenocyanate (11) with benzyl bromide and
Y = H, Br
5
6
HO
Et
Et
N N
N N
N
Se
O
N
Ph
N
Se
N
Ar
OH
8
7
Fig. 1. Structures of known 1-substituted 5-alkyl/arylselanyl-1H-tetrazoles.
1-Substituted 5-alkyl/arylselanyl-1H-tetrazoles can be also
prepared using double alkylation of sodium selenide. The major
disadvantage of these reactions lies in low selectivity, which causes
the formation of symmetrical selenides and low yields of the de-
sired products. 5-{[(1-Phenyl-1H-tetrazol-5-yl)selanyl]methyl}
uracil and its methyl derivative 3 were prepared using this pro-
tocol.21 5-Methylselanyl-1-phenyl-1H-tetrazole (4) was prepared
from 5-chloro-1-phenyl-1H-tetrazole by its reaction with bis(me-
thoxymagnesium)diselenide in methanol. However, the target
product was obtained in 14% yield only.22 Compounds with struc-
tures 5e8 and some of their derivatives were described in patents
connected with the development of photographic light-sensitive
materials.23e25
To investigate these sulfur/selenium bioisosteres in greater de-
tail, a general method of 1-substituted 5-alkyl/arylselanyl-1H-tet-
razoles synthesis, using easily available reactants and a simple
experimental procedure, is needed.
In this study we explored the possibility of the synthesis
of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles starting from alkyl/
arylisoselenocyanates, analogous with the simplest and most suc-
cessful approaches for the synthesis of 1-substituted 5-alkyl/aryl-
sulfanyl-1H-tetrazoles,14,26e28 starting from the corresponding

8800
G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
Table 2
Synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles prepared from alkyl/arylisoselenocyanates 10e15 by method 1
N N
R2X, TBAB
CH2Cl2
N N
R2
N
NaN3
R1
R1 NCSe
N
N
+
Se-
+
Se
N
Na
N
H2O, rt
N
R2
R1
R1
10-15
a
b
Entry
Substrate
R1
R2
X
Product
Yield [%]
a
b
1
2
3
4
5
6
7
8
9
10
11
10
12
13
14
14
15
15
15
Phe
4-CH3OPhe
Phe
4-BrPhe
CH3(CH2)3e
CH3(CH2)5e
CH3(CH2)5e
C6H11e
PhCH2e
PhCH2e
3,5-(NO2)2PhCH2e
3,5-(NO2)2PhCH2e
PhCH2e
CH3e
PhCH2e
CH3e
3,5-(NO2)2PhCH2e
2,4-(NO2)2PhCH2e
eBr
eBr
eCl
eCl
eBr
eOSO3CH3
eBr
eOSO3CH3
eCl
17
18
19
21
23
25
26
31
33
34
5
5
14
5
11
17
15
44
47
50
52
49
57
d
0
0
0
0
0
C6H11e
C6H11e
10
eCl
0
azide in different solvents were accomplished to find suitable
conditions for the synthesis of 5-alkylselanyl-1-aryl-1H-tetrazoles
(Table 3).
benzylselanyl-1-phenyl-1H-tetrazole (17a) were achieved in THF
or CH3CN, both with a small amount of water, at rt (Table 3, entries
4 and 7).
As shown in Table 3, almost all reactions of substrate 10 led
again to the formation of the target product 17a together with
cyanamide 17b, as in the case of method 1. Furthermore, another
unexpected side product was found, confirmed to be (Z)-Se-benzyl-
N-cyano-N,N0-diphenylisoselenourea (17c) by NMR and X-ray
crystallography experiments (Fig. 2). The highest yields of 5-
However, the main products of all these reactions were N-ben-
zyl-N-phenylcyanamide (17b) or (Z)-Se-benzyl-N-cyano-N,N0-
diphenylisoselenourea (17c). The reaction of the substrate 11 pro-
ceeded similarly, 5-benzylselanyl-1-(4-methoxyphenyl)-1H-tetra-
zole (18a), N-benzyl-N0-(4-methoxyphenyl)cyanamide (18b), and
(Z)-Se-benzyl-N-cyano-N,N0-bis(4-methoxyphenyl)isoselenourea
Table 3
One-pot reactions of arylisoselenocyanates 10 and 11 with azide anion under various reaction conditions
R
N N
N
NCSe
R
N
N
Se
PhCH2Br (0.7 equiv.)
azide donor (1.2 equiv.)
N
N
N
+
+
Se
N
R
R
R
(1 equiv.)
10 R = H
17a R = H
17b R = H
17c R = H
11 R = -OCH3
18a R = -OCH3
18b R = -OCH3
18c R = -OCH3
Entry
Substrate
Solvent
Water [%]
Azide donor
Temp
Product
Yield [%]
a
b
c
1
2
3
4
5
6
7
8
10
10
10
10
10
10
10
10
10
10
10
10
11
11
11
11
11
11
11
11
H2O
1,4-Dioxane
1,4-Dioxane
THF
THF
d
5
50
5
5
d
NaN3
NaN3
NaN3
NaN3
NaN3
TBAA
NaN3
NaN3
NaN3
NaN3
NaN3
(CH3)3SiN3
NaN3
NaN3
NaN3
Me3SiN3
TBAA
NaN3
NaN3
NaN3
rt
rt
rt
rt
17
17
17
17
17
17
17
17
17
17
17
17
18
18
18
18
18
18
18
18
4
10
3
22
5
5
17
7
16
4
0
56
0
0
10
2
23
19
3
71
56
47
65
Trace
12
51
4
ꢀ45 ꢁC
THF
rt
rt
CH3CN
CH3CN
CH3CN
CH2Cl2
C6H5N
(CH3)3SiN3
H2O
H2O
THF
THF
THF
5
5
ꢀ45 ꢁC
9
d
50
5
d
d
d
5
d
d
5
rt
rt
rt
rt
rt
rt
rt
56
64
10a
11
12
13
14b
15
16
17
18
19
20a
1
Decomposition
Decomposition
0
1
43
0
10
45
27
Trace
0
62
23
Trace
0
18
20
Trace
40
10
47
16
28
21
27
38
ꢀ60 ꢁC
rt
rt
rt
rt
CH3CN
DMF
CH2Cl2
5
50
a
Tetrabutylammonium bromide (TBAB) was used as phase-transfer catalyst.
b
Compound 11 was reacted with sodium azide and pyridine (1:1.2:3 molar ratio) in water for 3 h at rt, followed by addition of benzyl bromide (in 0.7 molar ratio) in THF.
Reaction mixture was stirred overnight.

G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
8801
Based on the aforementioned results we decided to use THF
(method 2) or CH3CN (method 3) as the solvents, both with 5% added
water, for the synthesis of a series of 1-substituted-5-alkylselanyl-
1H-tetrazoles. Moreover, the results achieved by these two methods
were compared with yields obtained by the one-pot reactions under
phase-transfer catalysis (method 4), which proceeded with the
highest yields of the side products, N-alkyl-N-arylcyanamides and
(Z)-Se-alkyl-N-cyano-N,N0-diarylisoselenoureas. Special attention
was paid to the synthesis of 1-substituted-5-[(dinitrobenzyl)
selanyl]-1H-tetrazoles, because many previous studies showed high
antimycobacterial activity of related mono/dinitro substituted
compounds.31e34
The results of the reactions of arylisoselenocyanates 10e12 are
summarized in Table 4. The target 1-aryl-5-[(3,5-dinitrobenzyl)
selanyl]-1H-tetrazoles (19e21a) were prepared as in previous cases
in low-to-moderate yields, which were not increased even by utili-
zation of 3,5-dinitrobenzyl iodide. Changes in the solvent system as
well as in the azide donor led again to a decrease in the yields of
products (e.g., product 19a was obtained in 21% yield by the reaction
of substrate 10 with 3,5-dinitrobenzyl iodide and sodium azide in the
mixture of CH3CN/H2O, 1:1, the side products 19b and 19c were ob-
tained in 39 and 11%, respectively; while the reaction of substrate 11
with 3,5-dinitrobenzyl iodide and TBAA in THF led to formation of
cyanamide 20b as the only product). In the case of the one-pot phase-
transfer catalyzed reaction (Table 4, method 4), 3,5-dinitrobenzyl
iodide had to be used to obtain reasonable yields. As all the re-
actions at temperatures below 0 ꢁC led to the formation of cyana-
mides as the main products, we decided to carry out the reaction
of 4-bromophenylisoselenocyanate with sodium azide and 3,5-
dinitrobenzyl iodide in THF at 55 ꢁC. In this case, 1-(4-bromo
phenyl)-5-[(3,5-dinitrobenzyl)selanyl]-1H-tetrazole (21a) was iso-
lated in 23% yield, and cyanamide 21b in 45% yield. Unfortunately,
none of the modifications of the reaction conditions or reactant ratios
improved the yields of the target 5-alkylselanyl-1-aryl-1H-tetrazoles.
Thusmethods 2 and3 are the methodsofchoicefor thepreparation of
1-substituted-5-alkylselanyl-1H-tetrazoles.
The results of the reactions of alkylisoselenocyanates 13e16 are
summarized in Table 5. In contrast to their aryl analogues, 1-alkyl-
5-alkylselanyl-1H-tetrazoles 22e34 were prepared in good yields
using one-pot reactions (methods 2 and 3), which are complete in
30 min to 3 h. Surprisingly, neither N,N-dialkyl cyanamides nor Se-
alkyl-N-cyano-N,N0-dialkylisoselenoureas were found regardless of
the method used. Tetrabutylammonium azide was also used in-
stead of sodium azide, but, as in the above-mentioned cases, this
change did not increase the product yields; tetrazole 32 was pre-
pared in 46% and its dinitro analogue 33 was not formed at
alldinseparable mixture of side products was formed.
In this work we demonstrated the enhanced reactivity of alkyl/
arylisoselenocyanates toward azide anion compared to alkyl/ary-
lisothiocyanates. Whereas reactions of alkyl/arylisothiocyanates
with azide anion lead exclusively to the formation of 1-alkyl/aryl-
1H-tetrazole-5-thiols, which can be further alkylated,28 1-alkyl/
aryl-1H-tetrazole-5-selenols are unstable compounds and only 1-
cyclohexyl-1H-tetrazole-5-selenol was partially isolated as its so-
dium salt. The attempts to alkylate sodium 1-alkyl/aryl-1H-tetra-
zole-5-selenolates in situ under phase-transfer catalysis conditions
led to the formation of 1-alkyl-5-alkylselanyl-1H-tetrazoles in
moderate yields, but 1-aryl-5-alkylselanyl-1H-tetrazoles were
formed only in very low yields due to unexpected formation of N-
alkyl-N-arylcyanamides (Table 2).
One-pot reactions of alkyl/arylisoselenocyanates with an azide
donor and alkylating agent significantly increased the yields of
target 1-substituted-5-alkylselanyl-1H-tetrazoles. In the case of
alkyl derivatives, good yields of the products 22e34 were achieved
(Table 5). In the case of aryl derivatives, the target tetrazoles
17e21a were formed in low-to-moderate yields (Tables 3 and 4),
Fig. 2. The molecular structure (ORTEP 50% probability level) of isoselenourea 17c.
Selected interatomic distances [A], angles and interplanar angle [ꢁ]: Se1eC1
ꢂ
1.9394(16), Se1eC2 1.9830(16), C1eN1 1.419(2), C1eN3 1.257(2), N1eC9 1.346(2),
C9eN2 1.147(2); C1eSe1eC2 100.29(7), Se1eC1eN1 112.29(11), Se1eC1eN3
130.25(12), C1eN1eC9 121.53(13), C1eN3eC16 123.17(14), N1eC9eN2 175.03(18);
Se1eC1eN3 versus C9eN1eC10 10.90(3).
(18c) were formed almost under any conditions. The highest yields
of the target tetrazole 18a were again achieved in THF or CH3CN
with a small amount of water (Table 3, entries 15 and 18). In-
terestingly, when one-pot reactions under phase-transfer catalysis
or in water were performed, the target tetrazoles 17a and 18a were
formed either in trace amounts or were not formed at all. As Table 3
demonstrates, variations in the obtained yields are high and hardly
predictable.
It should be noted that reactions in dry solvents and in a mixture
of organic solvent/water, 1:1 (v/v) proceeded with slightly lower
yields than in the case of using approx. 5% of water to dissolve
sodium azide before its addition to reaction mixture.
The formation of the unexpected N-alkyl-N-arylcyanamides and
(Z)-Se-alkyl-N-cyano-N,N0-diarylisoselenoureas explains the re-
lease of elemental selenium in all these reactions. We suggest that
after the addition of the azide anion to arylisoselenocyanate, ni-
trogen together with selenium could be released and sodium
N-cyano-N-arylamide (I) formed (Scheme 2). This anion could
be subsequently alkylated to form N-alkyl-N-arylcyanamide (II)
or it could react with another molecule of arylisoselenocyanate
and, after alkylation, produce (Z)-Se-alkyl-N-cyano-N,N0-diary-
lisoselenourea (III).
-Se
N-
N+
C N
Se
-
-Se
N
N3
C
N
N
C
N
Ar
N
-Se
-N2
Ar
N
Ar
N
N
N-
RCH2X
-X-
C
C
C
N-
Ar
N
Ar
N
Ar
R
I
II
ArNCSe
Ar
Ar
N
N
N
N
RCH2X
-X-
C
C
N
Ar
-Se
Se
R
N
Ar
III
Scheme 2. Formation of side products of the reactions of arylisoselenocyanates with
azide anion.

8802
G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
Table 4
Reactions of arylisoselenocyanates 10e12 with sodium azide and 3,5-dinitrobenzyl halide by methods 2, 3, and 4
R
NO2
N N
N
NCSe
R
X
O2N
N
N
Se
N
R
N
N
NaN3 (1.2 equiv.)
O2N
+
+
+
Se
N
R
NO2
NO2
NO2
O2N
NO2
R
(1 equiv.)
(0.7 equiv.)
10 R = H
19a R = H
19b R = H
19c R = H
11 R = -OCH3
12 R = -Br
20a R = -OCH3
21a R = -Br
20b R = -OCH3
21b R = -Br
20c R = -OCH3
21c R = -Br
Substrate
Product
Yield [%]
Method 2
Method 3
Method 4
X¼Cl
X¼I
X¼Cl
X¼I
X¼I
10
10
10
11
11
11
12
12
12
19a
19b
19c
20a
20b
20c
21a
21b
21c
15
33
2
33
40
5
12
0
0
28
31
15
19
62
19
34
20
0
28
8
2
33
60
0
5
0
0
30
17
32
5
44
4
11
15
36
16
27
22
Trace
43
16
17
26
20
Furthermore, isoselenoureas 17c and 19c (Figs. 2 and 3) were
characterized using X-ray crystallography. Both compounds crys-
tallized in the triclinic space group P-1, isoselenourea 17c with two
molecules within the unit cell, while its dinitro analogue 19c
crystallized with two independent molecules and with four mole-
cules within the triclinic unit cell. To the best of our knowledge,
analogous structures are still elusive in the literature; only several
cyclic isoselenoureas (e.g., A,35,36 B,37,38 C,39,40 D,41,42 E,35,43 F,44,45
G46,47), which resemble the structural motif of compounds 17c
and 19c, were found within the crystallographic database (Fig. 4).
These compounds reveal rather similar distances and angles of
interest within various ring arrangements to the isoselenoureas 17c
and 19c. The lack of conjugation is seen from the separation of C
and N atoms in both molecules of 17c and 19c, and thus the double
Table 5
Synthesis and yields of 1-alkyl-5-alkylselanyl-1H-tetrazoles (22e34) prepared by
methods 2, 3, and 4
R2X (0.9 equiv.)
NaN3 (1.2 equiv.)
N N
R2
Se
R1 NCSe
N
org.solvent, H2O, rt
N
R1
(1 equiv.)
13-16
22-34
R2 = CH3, X = OSO3CH3; R2 = PhCH2, X = Br; R2 = 3,5-(NO2)2PhCH2, X = Cl
Substrate Product R1
R2
Yield [%]
Method Method Method
2
3
4
13
13
13
14
14
14
16
16
16
15
15
15
15
22
23
24
25
26
27
28
29
30
31
32
33
34
CH3(CH2)3e CH3e
CH3(CH2)3e PhCH2e
CH3(CH2)3e 3,5-(NO2)2PhCH2e 44
CH3(CH2)5e CH3e
CH3(CH2)5e PhCH2e
CH3(CH2)5e 3,5-(NO2)2PhCH2e 30
CH3(CH2)7e CH3e
CH3(CH2)7e PhCH2e
50
73
59
d
d
d
54
d
61
25
d
d
d
d
30
66
41
84
45
48
74
71
d
57
58
54
56
CH3(CH2)7e 3,5-(NO2)2PhCH2e 38
C6H11e
C6H11e
C6H11e
C6H11e
CH3e
PhCH2e
3,5-(NO2)2PhCH2e 38
2,4-(NO2)2PhCH2e
73
76
65
68
57
a
a
a
a
Unseparable mixture. TLC showed the formation of 34 in insignificant amount
only.
because these reactions again proceeded via the formation of N-
alkyl-N-arylcyanamides (17e21b) and, surprisingly, (Z)-Se-alkyl-N-
cyano-N,N0-diarylisoselenoureas (17e21c) as the main products.
In general, alkyl substituents stabilized the 1-alkyl-1H-tetra-
zole-5-selenolates formed after the addition of the azide anion to
isoselenocyanates and facilitated the formation of 1-alkyl-5-
alkylselanyl-1H-tetrazoles. On the other hand, aryl substituents
facilitated the decomposition of 1-aryl-1H-tetrazole-5-selenolates
leading to the formation of side products, N-alkyl-N-arylcyana-
mides and (Z)-Se-alkyl-N-cyano-N,N0-diarylisoselenoureas.
Fig. 3. The molecular structure (ORTEP 50% probability level) ꢁof isoselenourea 19c.
ꢂ
Selected interatomic distances [A], angles and interplanar angle [ ] for molecules A and
B (appropriate parameters are given in parentheses): Se1eC1 1.934(2) (1.930(2)),
Se1eC2 1.9737(19) (1.972(2)), C1eN3 1.427(2) (1.421(3)), C1eN5 1.255(3) (1.256(3)),
N3eC9 1.347(3) (1.343(3)), C9eN4 1.145(3) (1.143(3)); C1eSe1eC2 97.62(8)(97.65(8)),
Se1eC1eN3 114.71(14) (115.44(14)), Se1eC1 N5 127.31(15) (126.86(16)), C1eN3eC9
119.91(16) (120.78(17)), C1eN5eC16 123.19(18) (122.73(18)), N3eC9eN4 175.9(2);
Se1eC1eN5 versus C9eN3eC10 22.28(2) (16.76(3)).

G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
8803
One-pot reactions of arylisoselenocyanates with sodium azide
and an alkylating agent led unexpectedly to the formation of
N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N0-diaryliso
selenoureas as the main products, while 1-aryl-5-alkylselanyl-1H-
tetrazoles were formed only in low yields. Nevertheless, when
alkylisoselenocyanates were utilized as the substrates, the re-
actions led exclusively to the formation of 1-alkyl-5-alkylselanyl-
1H-tetrazoles in good yields.
N
N
N
N
N
N
N
N
Se
Se
Se
Se
A
B
C
D
N
N
N
N
N
N
Se
Se
Se
Simple and general methods described in this work bring new
possibilities for the synthesis of these selenium-containing com-
pounds and can be used in the synthesis and further investigations
of biologically active sulfur/selenium bioisosteres.
E
F
G
Fig. 4. Structural motifs of compounds similar to isoselenoureas 17c and 19c found in
the crystallographic database.
and triple bonds between carbon and nitrogen can be surely
assigned (Figs. 2 and 3).
4. Experimental section
4.1. General
In the crystal packing of isoselenoureas 17c and 19c (Figs. 5
and 6), no structurally interesting interatomic nor
pep in-
teractions were observed. On the other hand, along the a-axis, an
intriguing supramolecular architecture is detected. In the case of
17c, a dimer-like structure is formed (Fig. 5), while in the case of
19c, its molecules are mutually oriented in layers (Fig. 6) with
alternating domains of selenium and oxygen atoms.
All chemicals for synthesis were obtained from SigmaeAldrich
(Schnelldorf, Germany) and used as received. TLC was performed
on Merck aluminum sheets with silica gel 60 F254 and/or
Merck aluminum sheets with silica gel 60 RP-18 F254s. Merck Kieselgel
60 (0.040e0.063 mm) and/or Merck LiChroprep RP-18 (0.015
e0.025 mm) were used for column chromatography. Melting points
€
were recorded on a Buchi B-545 apparatus and are uncorrected. In-
frared spectra were measured on a Nicolet 6700 (ATR mode). 1H and
13C NMR spectra were recorded on Varian Mercury Vx BB 300 or
VNMR S500 NMR spectrometers. Chemical shifts were reported as
d
values in parts per million (ppm) and were indirectly referenced to
tetramethylsilane (TMS) via the solvent signal. The elemental analysis
was carried out on Automatic Microanalyser EA1110CE (Fisons In-
struments S.p.A., Milano, Italy). Electrospray ionization mass spec-
troscopic (ESI MS) experiments were performed using Acquity UPLC
with MS/MS Quattro Micro detection (MicromassþWaters). High-
resolution mass spectra were recorded on VG-Analytical ZAB-SEQ.
4.2. Crystallography
The X-ray data for the colorless and yellowish crystals of iso-
selenoureas 17c and 19c were obtained at 150 K using an Oxford
Cryostream low-temperature device on a Nonius KappaCCD dif-
ꢂ
fractometer with Mo K
a
radiation (
and
l
¼0.71073 A), a graphite
Fig. 5. Crystal packing of isoselenourea 17c view along axis a.
monochromator, and the
f
c
scan mode. Data reductions were
performed with DENZO-SMN.48 The absorption was corrected by
integration methods.49 Structures were solved by direct methods
(Sir92)50 and refined by full matrix least-square based on F2
(SHELXL97).51 Hydrogen atoms were mostly localized on a differ-
ence Fourier map, however, to ensure uniformity of treatment of
crystal, all hydrogens were recalculated into idealized positions
(riding model) and assigned temperature factors Hiso(H)¼1.2 Ueq(-
ꢂ
pivot atom) with CeH¼0.97 and 0.93 A for methylene and hydro-
gen atoms in aromatic rings.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
P
P
P
P
Rint
¼
F2 ꢀ Fo2;mean
=
Fo2; GOF ¼ ½ ðwðFo2 ꢀ Fc2Þ2Þ=
o
P
P
ðNdiffrs ꢀ NparamsÞꢂ1=2 for all data, R(F)¼ rrForꢀrFcrr/ rForfor ob-
P
served data, wRðF2Þ ¼ ½ ðwðFo2 ꢀ Fc2Þ2Þ=ð wðFo2Þ2Þꢂ1=2 for all data.
Crystallographic data for structural analysis have been de-
posited with the Cambridge Crystallographic Data Centre, CCDC no.
928734 and 928735 for 17c and 19c, respectively. Copies of this
information may be obtained free of charge from The Director,
CCDC, 12 Union Road, Cambridge CB2 1EY, UK (fax: þ44 1223
336033; e-mail: deposit@ccdc.cam.ac.uk or website: http://
www.ccdc.cam.ac.uk).
Fig. 6. Crystal packing of isoselenourea 19c view along axis a.
3. Conclusions
Single crystals of isoselenoureas 17c and 19c were of sufficient
quality for X-ray diffraction techniques. The crystallographic data
and structure refinement parameters for compound 17c are:
In this work, the synthesis of 1-substituted-5-alkylselanyl-1H-
tetrazoles from alkyl/arylisoselenocyanates has been described.

8804
G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
ꢂ
C21H17N3Se,
M¼390.34,
triclinic,
P-1,
a¼9.0471(5)
A,
CH2Cl2 and then for 5.5 h after the addition of selenium powder.
Mobile phase: hexane/EtOAc, 30:1. Yield: 67% as slightly yellow
¼83.622(4)ꢁ,
b
¼68.472(3)ꢁ,
ꢂ
ꢂ
b¼10.6140(5) A, c¼10.6470(3) A,
a
3
¼68.326(4)ꢁ, Z¼2, V¼883.47(8) A , Dc¼1.467
g
cmꢀ3
,
viscous oil. 1H NMR (500 MHz, CDCl3)
d
3.59 (2H, t, J¼6.6 Hz),
ꢂ
g
m
¼2.133 mmꢀ1, Tmin/Tmax¼0.519/0.739; ꢀ11ꢃhꢃ11, ꢀ13ꢃkꢃ13,
1.74e1.67 (2H, m),1.50e1.41 (2H, m), 0.94 (3H, t, J¼7.3 Hz); 13C NMR
ꢀ13ꢃlꢃ13; 18,954 reflections measured (qmax¼27.49ꢁ), 18,869 in-
(125 MHz, CDCl3): d 121.82 (NCSe), 45.11, 31.30, 19.66, 13.13. IR
dependent (Rint¼0.0226), 3769 with I>2
s
(I), 226 parameters,
(KBr): 2959, 2938, 2873, 2140 (s, NCSe), 1736, 1458, 1446, 1344,
S¼1.098, R1(obsd data)¼0.0246, wR2(all data)¼0.0612; max., min.
1116, 743 cmꢀ1
.
ꢂꢀ3
residual electron density¼0.527, ꢀ0.775 e A
.
Crystallographic data for compound 19c: C21H15N5O4Se,
4.3.5. Hexylisoselenocyanate (14).55 The refluxing mixture was
stirred for 4.5 h after the addition of the solution of triphosgene in
CH2Cl2 and then for 8 h after the addition of selenium powder.
Mobile phase: hexane/EtOAc, 30:1. Yield: 43% as slightly yellow
ꢂ
ꢂ
M¼480.34, triclinic, P-1, a¼12.7870(9) A, b¼13.1701(10) A,
c¼14.4670(9) A,
a
3
¼78.456(6)ꢁ,
b
¼68.953(4)ꢁ,
g
¼63.744(6)ꢁ, Z¼4,
ꢂ
V¼2036.7(3) A , Dc¼1.566
g
cmꢀ3
,
m
¼1.883 mmꢀ1
, Tmin/
ꢂ
Tmax¼0.549/0.772; ꢀ16ꢃhꢃ16, ꢀ17ꢃkꢃ17, ꢀ18ꢃlꢃ18; 44,792 re-
viscous oil. 1H NMR (500 MHz, CDCl3):
d
3.58 (2H, t, J¼6.6 Hz),
flections
(Rint¼0.0296), 7683 with I>2
measured
(
qmax¼27.5ꢁ),
44,722
independent
1.75e1.68 (2H, m), 1.45e1.37 (2H, m), 1.36e1.26 (4H, m), 0.89 (3H, t,
s
(I), 559 parameters, S¼1.116, R1(obsd
J¼6.9 Hz); 13C NMR (125 MHz, CDCl3):
d 121.87 (NCSe), 45.42, 30.82,
29.35, 26.12, 22.33, 13.87. IR (KBr): 2955, 2928, 2858, 2138 (s, NCSe),
data)¼0.0298, wR2(all data)¼0.0570; max., min. residual electron
ꢂꢀ3
density¼0.362, ꢀ0.382 e A
.
1449, 1344, 726 cmꢀ1
.
4.3. Synthesis of alkyl/arylisoselenocyanates (10e16)
4.3.6. Cyclohexylisoselenocyanate (15).56 Cyclohexylisoselenocyanate
was prepared from commercially available cyclohexyl isocyanide. A
mixture of cyclohexyl isocyanide (1 g, 9.16 mmol) and selenium
powder (1.45 g, 18.32 mmol) in dry CH2Cl2 (15 ml) was stirred at
reflux for 3 h. After completion, as determined by TLC, the solvent
was evaporated under reduced pressure and the crude product was
purified by silica gel column chromatography (hexane/EtOAc, 50:1).
Yield: 98% (1.69 g, 8.98 mmol) as slightly yellow viscous oil. 1H NMR
4.3.1. Phenylisoselenocyanate (10).52 To a refluxing mixture of the
N-phenylformamide (1 g, 8.25 mmol) and triethylamine (3.59 g,
4.95 ml, 35.49 mmol) in CH2Cl2 (35 ml) a solution of triphosgene
(1.3 g, 4.37 mmol) in CH2Cl2 (15 ml) was added dropwise over
a period of 1 h. After the addition was complete, the mixture was
stirred at reflux for an additional 3 h until the starting material
disappeared, as determined by TLC. Selenium powder (1.3 g,
16.5 mmol) was then added, and the mixture was refluxed for an
additional 12 h. The formation of isoselenocyanate could be ob-
served by formation of an orange spot on TLC (after oxidation on
air). After completion, the mixture was cooled, filtered, and the
precipitate on the filter was washed with EtOAc. The organic so-
lution was evaporated under reduced pressure and the residue was
purified by silica gel column chromatography (mobile phase: hex-
ane) to give 0.95 g (5.2 mmol, 63%) of 10 as a yellow viscous oil. 1H
(300 MHz, CDCl3):
d
3.84e3.74 (1H, m), 1.95e1.87 (2H, m), 1.79e1.63
121.65
(4H, m), 1.54e1.32 (4H, m); 13C NMR (75 MHz, CDCl3):
d
(NCSe), 55.85, 32.65, 24.88, 23.01. IR (KBr): 2933, 2855, 2114 (s, NCSe),
2065, 1448, 1361, 1318, 1126, 1048, 891, 671 cmꢀ1
4.3.7. Octylisoselenocyanate (16). The refluxing mixture was stirred
for 3 h after the addition of the solution of triphosgene in CH2Cl2
and then for 5 h after the addition of selenium powder. Mobile
phase: hexane/EtOAc, 35:1. Yield: 67% as slightly yellow viscous oil.
NMR (500 MHz, CDCl3):
NMR (125 MHz, CDCl3):
126.06. IR (KBr): 2110 (s, NCSe), 2049, 1588, 1487, 1070, 907, 845,
748, 683 cmꢀ1
d
7.40e7.31 (3H, m), 7.30e7.27 (2H, m); 13
129.68, 129.54, 129.31 (NCSe), 128.07,
C
1H NMR (300 MHz, CDCl3):
d
3.59 (2H, t, J¼6.7 Hz), 1.77e1.68 (2H,
d
m), 1.47e1.21 (10H, m), 0.89 (3H, t, J¼6.8 Hz); 13C NMR (75 MHz,
CDCl3):
d 121.70 (NCSe), 45.42, 31.64, 29.36, 28.97, 28.65, 26.47,
.
22.56, 14.03. IR (KBr): 2924, 2855, 2135 (s, NCSe), 1737, 1456, 1343,
1116, 722 cmꢀ1; HRMS m/z (CI) calcd for C9H17NSeþHþ (MþHþ)
220.0599, found 220.0595.
Isoselenocyanates 11e14 and 16 were prepared according to
procedure in Section 4.3.1.
4.3.2. 4-Methoxyphenylisoselenocyanate (11).53 The refluxing mix-
ture was stirred for 3 h after the addition of the solution of tri-
phosgene in CH2Cl2 and then for 6 h after the addition of selenium
powder. Mobile phase: hexane/EtOAc, 35:1. Yield: 68% as slightly
pink solid; mp 49e50 ꢁC (lit.53 50e51 ꢁC). 1H NMR (500 MHz,
4.4. Synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles
4.4.1. General procedures. Dimethylsulfate, benzyl bromide, 3,5-
dinitrobenzyl chloride, and 3,5-dinitrobenzyl iodide were used as
alkylating agents.
CDCl3):
d
7.22 (2H, d, J¼9.0 Hz), 6.86 (2H, d, J¼9.0 Hz), 3.81 (3H, s);
13C NMR (125 MHz, CDCl3):
d
159.13, 127.37 (2C, NCSeþAr), 122.14,
4.4.2. Method 1. Isoselenocyanate (1 mmol) and sodium azide
(1.2 mmol) in water (7 ml) were stirred for 12e24 at rt until
completion, as determined by TLC (for Rf values see later). Pre-
cipitated selenium was filtered off and the aqueous solution was
washed with EtOAc (2ꢄ10 ml). The alkylating agent (0.7 mmol) and
TBAB (0.035 mmol) in CH2Cl2 (7 ml) were added to the aqueous
solution. The reaction mixture was gently stirred at rt overnight.
The organic phase was separated, washed with water (2ꢄ10 ml),
and dried over anhydrous sodium sulfate. The solvent was evapo-
rated and the crude products were separated and purified by col-
umn chromatography on silica gel.
114.79, 55.57. IR (KBr): 2993, 2955, 2930, 2834, 2116 (s, NCSe), 2058,
1877, 1502, 1452, 1441, 1303, 1248, 1166, 1105, 1028, 820, 759,
702 cmꢀ1
.
4.3.3. 4-Bromophenylisoselenocyanate (12).45 The refluxing mix-
ture was stirred for 4.5 h after the addition of the solution of tri-
phosgene in CH2Cl2 and then for 12 h after the addition of selenium
powder. Mobile phase: hexane. Yield: 58% as white crystalline
solid; mp 80e81 ꢁC. 1H NMR (500 MHz, DMSO):
d 7.66 (2H, d,
J¼8.6 Hz), 7.47 (2H, d, J¼8.6 Hz); 13C NMR (126 MHz, DMSO):
d
132.98, 129.66 (NCSe), 128.52, 128.31, 121.60. IR (KBr): 3083, 2119
(s, NCSe), 2050, 1479, 1398, 1069, 1011, 845, 816 cmꢀ1. Anal. Calcd
for C7H4BrNSe: C, 32.22; H, 1.54; N, 5.37. Found: C, 32.03; H, 1.83;
N, 5.45.
4.4.3. Method 2. To the solution of isoselenocyanate (1 mmol) and
alkylating agent (0.7 mmol for arylisoselenocyanates/0.9 mmol for
alkylisoselenocyanates) in THF (10 ml), sodium azide (1.2 mmol) in
water (0.5 ml) was added. The reaction mixture was stirred until
the starting isoselenocyanate disappeared, as determined by TLC.
After completion, the THF was evaporated, the crude product was
4.3.4. Butylisoselenocyanate (13).54 The refluxing mixture was
stirred for 4.5 h after the addition of the solution of triphosgene in

G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
8805
dissolved in EtOAc (10 ml), and washed with water (2ꢄ10 ml). The
organic phase was dried over anhydrous sodium sulfate. The sol-
vent was evaporated under reduced pressure and the crude prod-
ucts were purified by silica gel column chromatography and/or
reverse phase column chromatography (see later).
LRMS m/z (ESI) 346.7 (100, MHþ), 344.8 (50), 342.8 (20%); HRMS m/
z (ESI) calcd for C15H14N4OSeþHþ (MþHþ) 347.04056, found
347.04056.
4.5.5. N-Benzyl-N-(4-methoxyphenyl)cyanamide (18b). White crys-
talline solid; mp 60 ꢁC. Rf (hexane/EtOA, 3:1) 0.43, Rf (RP-18; MeCN/
4.4.4. Method 3. This method is same as method 2, only acetoni-
trile was used instead of THF.
H2O, 2:1) 0.41. 1H NMR (300 MHz, CDCl3):
d 7.43e7.31 (5H, m), 7.05
(2H, d, J¼9.1 Hz), 6.86 (2H, d, J¼9.1 Hz), 4.74 (2H, s), 3.77 (3H, s); 13C
NMR (75 MHz, CDCl3):
d 156.26, 134.47, 133.07, 129.00, 128.47,
4.4.5. Method 4. Isoselenocyanate (1 mmol) and alkylating agent
(0.7 mmol for arylisoselenocyanates/0.9 mmol for alkylisoseleno-
cyanates) in CH2Cl2 (7 ml) and sodium azide (1.2 mmol) in H2O
(7 ml) were stirred in the presence of TBAB (0.035/0.045 mmol for
aryl/alkylisoselenocyanate, respectively) at rt until completion
(usually overnight). The organic phase was then separated, washed
with water (2ꢄ10 ml), and dried over anhydrous sodium sulfate.
The solvent was evaporated and the crude product was purified by
column chromatography on silica and/or reverse phase column
chromatography (see later).
127.47, 118.25, 114.83, 55.53, 54.64. IR (KBr): 2956, 2926, 2359, 2212
(s, C^N), 1509, 1453, 1373, 1291, 1230, 1178, 1019, 821, 740, 703,
684 cmꢀ1. Anal. Calcd for C15H14N2O: C, 75.61; H, 5.92; N, 11.76.
Found: C, 75.73; H, 6.05; N, 12.03.
4.5.6. (Z)-Se-Benzyl-N-cyano-N,N0-di(4-methoxyphenyl)iso-
selenourea (18c). Yellow viscous oil. Rf (hexane/EtOAc, 3:1) 0.35, Rf
(RP-18; MeCN/H2O, 2:1) 0.19. 1H NMR (300 MHz, acetone):
d
7.35e7.20 (7H, m), 7.00 (2H, d, J¼9.0 Hz), 6.88 (2H, d, J¼8.8 Hz),
6.78 (2H, d, J¼9.0 Hz), 4.03 (2H, s), 3.83 (3H, s), 3.76 (3H, s); 13C
NMR (75 MHz, acetone):
d 160.69, 157.84, 145.20, 141.90, 138.39,
4.5. 5-Alkylselanyl-1-aryl-1H-tetrazoles (17e21b)
131.28, 129.82, 129.50, 128.66, 128.31, 122.57, 115.56, 114.86, 111.96,
55.91, 55.64, 32.01; 15N NMR (50.7 MHz, CDCl3):
d
296.5, 214.1,
Yields of the products are given in Tables 2e4.
Compounds 17a, 17b, and 17c were separated by reverse phase
column chromatography, mobile phase: MeCN/H2O, 2:1.
103.4. IR (KBr): 2956, 2835, 2222 (C^N), 1621, 1504, 1292, 1242,
1177, 1077, 1031, 831, 697 cmꢀ1. LRMS m/z (ESI) 451.7 (100, MHþ),
449.8 (52), 452.7 (28), 448.8 (21.5%); HRMS m/z (ESI) calcd for
C23H21N3O2SeþHþ (MþHþ) 452.08718, found 452.08711.
4.5.1. 5-Benzylselanyl-1-phenyl-1H-tetrazole (17a). Beige solid; mp
71 ꢁC. Rf (hexane/EtOAc, 3:1) 0.72, Rf (RP-18; MeCN/H2O, 2:1) 0.27.
Compounds 19a, 19b, and 19c were separated by silica gel col-
umn chromatography, mobile phase: hexane/EtOAc, 10:1.
1H NMR (300 MHz, CDCl3):
d
7.55e7.44 (5H, m, Ar), 7.42e7.36 (2H,
m, Ar), 7.33e7.24 (3H, m, Ar), 4.68 (s, 2H); 13C NMR (75 MHz, CDCl3)
147.18, 136.24, 133.94, 130.20, 129.75, 129.11, 128.80, 127.91,
4.5.7. 5-(3,5-Dinitrobenzylselanyl)-1-phenyl-1H-tetrazole
Light beige crystalline solid; mp 141e143 ꢁC (with decomposition).
Rf (hexane/EtOAc, 3:1) 0.18. 1H NMR (300 MHz, acetone):
8.85 (2H,
d, J¼2.1 Hz), 8.80 (1H, t, J¼2.1 Hz), 7.78e7.39 (5H, m), 4.95 (2H, s);
13C NMR (75 MHz, acetone):
149.29, 147.59, 144.56, 134.88, 131.44,
(19a).
d
123.88, 32.56. IR (KBr): 3030, 2922, 1595, 1497, 1374, 1233, 1089,
1014, 973, 765, 693 cmꢀ1. Anal. Calcd for C14H12N4Se: C, 53.34; H,
3.84; N, 17.77. Found: C, 53.25; H, 3.98; N, 17.53.
d
d
130.88, 130.46, 125.20, 118.29, 30.39. IR (KBr): 3098, 1536 (NO2),
1499, 1342 (NO2), 1232, 1093, 1036, 914, 809, 771, 734, 692,
672 cmꢀ1. Anal. Calcd for C14H10N6O4Se: C, 41.50; H, 2.49; N, 20.74.
Found: C, 41.32; H, 2.71; N, 20.47.
4.5.2. N-Benzyl-N-phenylcyanamide (17b).57 White crystalline
solid; mp 62 ꢁC (lit.57 59e60 ꢁC). Rf (hexane/EtOAc, 3:1) 0.75, Rf (RP-
18; MeCN/H2O, 2:1) 0.33. 1H NMR (300 MHz, CDCl3):
d
7.45e7.30
(7H, m, Ar), 7.17e7.05 (3H, m, Ar), 4.81 (2H, s); 13C NMR (75 MHz,
CDCl3): 139.76, 134.25, 129.62, 129.06, 128.50, 127.31, 123.67,
115.98, 113.90, 53.70. IR (KBr): 3030, 2925, 2216 (s, C^N), 1599,
1494, 1453, 1367, 1233, 1181, 1078, 930, 878, 766, 718, 686 cmꢀ1
d
4.5.8. N-(3,5-Dinitrobenzyl)-N-phenylcyanamide (19b). Yellowish
solid; mp 174e176 ꢁC. Rf (hexane/EtOAc, 3:1) 0.28. 1H NMR
.
(300 MHz, acetone):
7.46e7.39 (2H, m), 7.31e7.26 (2H, m), 7.18e7.11 (1H, m), 5.38 (2H,
s); 13C NMR (75 MHz, acetone):
149.76, 140.98, 140.39, 130.78,
d
8.92 (1H, t, J¼2.1 Hz), 8.76 (2H, d, J¼2.1 Hz),
Anal. Calcd for C14H12N2: C, 80.74; H, 2.81; N,13.45. Found: C, 80.40;
H, 2.52; N, 13.62. LRMS m/z (ESI) 208.88 (100, MHþ), 209.89 (15%).
d
128.85, 124.89, 119.28, 116.86, 113.66, 52.39. IR (KBr): 3115, 2921,
2360, 2221 (s, C^N),1597,1538 (NO2), 1492, 1342 (NO2),1234,1188,
1083, 903, 810, 763, 723, 696, 666 cmꢀ1. Anal. Calcd for C14H10N4O4:
C, 56.38; H, 3.38; N, 18.78. Found: C, 56.3; H, 3.56; N, 18.88.
4.5.3. (Z)-Se-Benzyl-N-cyano-N,N0-diphenylisoselenourea
(17c). White crystalline solid; mp 97e98 ꢁC. Rf (hexane/EtOAc, 3:1)
0.8, Rf (RP-18; MeCN/H2O, 2:1) 0.12. 1H NMR (300 MHz, CDCl3):
d
7.44e7.08 (13H, m, Ar), 6.79e6.71 (2H, m, Ar), 4.05 (2H, s); 13C
NMR (75 MHz, CDCl3):
d
147.54, 144.34, 137.35, 136.59, 129.55,
4.5.9. (Z)-Se-(3,5-Dinitrobenzyl)-N-cyano-N,N0-diphenylisoselenourea
129.11, 128.91, 128.74, 128.25, 127.72, 125.03, 124.76, 120.42, 111.20,
(19c). Yellowish solid; mp 130 ꢁC. Rf (hexane/EtOAc, 3:1) 0.39. 1H
31.96. IR (KBr): 2223 (s, C^N), 1627, 1587, 1486, 1240, 1231, 1187,
NMR (300 MHz, acetone):
d
8.81 (1H, t, J¼2.2 Hz), 8.54 (2H, d,
1163, 1077, 851, 751, 690 cmꢀ1
;
HRMS m/z (ESI) calcd for
J¼2.2 Hz), 7.53e7.38 (5H, m), 7.32e7.24 (2H, m), 7.14e7.07 (1H, m),
C21H17N3SeþHþ (MþHþ) 392.06605, found 392.06597. Anal. Calcd
for C21H17N3Se: C, 64.62; H, 4.39; N, 10.77. Found: C, 64.58; H, 4.79;
N, 10.86.
6.84e6.78 (2H, m), 4.42 (2H, s); 13C NMR (75 MHz, acetone):
d
149.37, 148.32, 144.24, 144.09, 138.50, 130.61, 129.97, 129.77,
129.47, 126.34, 125.59, 121.30, 118.31, 111.33, 30.26. IR (KBr): 3087,
2963, 2922, 2220 (C^N), 1651, 1592, 1537 (NO2), 1488, 1343 (NO2),
1237, 1183, 1076, 912, 853, 809, 754, 695 cmꢀ1. Anal. Calcd for
C21H15N5O4Se: C, 52.51; H, 3.15; N, 14.58. Found: C, 52.46; H, 3.32;
N, 14.30; HRMS m/z (ESI) calcd for C21H15N5O4SeþHþ (MþHþ)
482.03620, found 482.03618.
Compounds 18a, 18b, and 18c were separated by reverse phase
column chromatography, mobile phase: MeCN/H2O, 2:1.
4.5.4. 5-Benzylselanyl-1-(4-methoxyphenyl)-1H-tetrazole
(18a). Yellowish viscous oil. Rf (hexane/EtOAc, 3:1) 0.34, Rf (RP-18;
MeCN/H2O, 2:1) 0.28. 1H NMR (300 MHz, acetone):
d
7.47e7.40 (4H,
m, Ar), 7.32e7.20 (3H, m, Ar), 7.17e7.10 (2H, m), 4.64 (2H, s), 3.88
(3H, s); 13C NMR (75 MHz, acetone):
161.96, 148.22, 138.71, 129.92,
129.42, 128.40, 127.62, 126.99, 115.71, 56.08, 32.53. IR (KBr): 3062,
2837, 1608, 1515, 1454, 1377, 1258, 1171, 1023, 834, 761, 698 cmꢀ1
Compounds 20a, 20b, and 20c were separated by silica gel col-
umn chromatography, mobile phase: hexane/EtOAc, 7:1.
d
4.5.10. 5-(3,5-Dinitrobenzylselanyl)-1-(4-methoxyphenyl)-1H-tetra-
zole (20a). Brownish solid; mp 131e132 ꢁC (with decomposition).
.

8806
G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
Rf (hexane/EtOAc, 3:1) 0.12. 1H NMR (500 MHz, acetone):
d
8.83 (2H,
calcd for
659.83855.
C
21H13Br2N5O4SeþNaþ (MþNaþ) 659.83917, found
d, J¼2.1 Hz), 8.80 (1H, t, J¼2.1 Hz), 7.48 (2H, d, J¼9.0 Hz), 7.14 (2H, d,
J¼9.0 Hz), 4.91 (2H, s), 3.89 (3H, s); 13C NMR (125 MHz, acetone):
d
162.07,149.27,147.77,144.63,130.42,127.39,126.94,118.26, 115.81,
4.6. 1-Alkyl-5-alkylselanyl-1H-tetrazoles (22e34)
Yields of the products are given in Tables 2 and 5.
56.11, 30.26. IR (KBr): 3089, 2923,1608,1591,1537 (NO2),1511,1446,
1342 (NO2), 1257, 1173, 1020, 913, 839, 730, 672 cmꢀ1. Anal. Calcd
for C15H12N6O5Se: C, 41.39; H, 2.78; N, 19.31. Found: C, 41.59; H,
2.41; N, 19.0.
4.6.1. 1-Butyl-5-methylselanyl-1H-tetrazole (22). Yellowish viscous
oil. 1H NMR (300 MHz, CDCl3):
d
4.24 (2H, t, J¼7.2 Hz), 2.72 (3H, s),
4.5.11. N-(3,5-Dinitrobenzyl)-N-(4-methoxyphenyl)cyanamide
1.92e1.82 (2H, m), 1.42e1.30 (2H, m), 0.96 (3H, t, J¼7.3 Hz); 13C
(20b). Yellowish solid; mp 121e122 ꢁC. Rf (hexane/EtOAc, 3:1) 0.24.
NMR (75 MHz, CDCl3): d 146.45, 47.70, 31.14, 19.57, 13.36, 8.13. IR
1H NMR (500 MHz, acetone):
d
8.91 (1H, t, J¼2.1 Hz), 8.73 (2H, d,
J¼2.1 Hz), 7.23 (2H, d, J¼9.2 Hz), 6.97 (2H, d, J¼9.2 Hz), 5.28 (2H, s),
3.76 (3H, s); 13C NMR (125 MHz, acetone):
157.70, 149.73, 141.15,
(KBr): 2960, 2935, 2874, 2218 (w), 1458, 1428, 1383, 1275, 1186,
1078, 978, 925, 753 cmꢀ1. LRMS m/z (ESI) 220.7 (100, MHþ), 218.9
(52), 216.8 (20%); HRMS m/z (ESI) calcd for C6H12N4SeþHþ (MþHþ)
221.02999, found 221.02997.
d
133.51, 128.97, 119.37, 119.25, 115.92, 114.53, 55.83, 53.32. IR (KBr):
3091, 2839, 2218 (s, C^N), 1596, 1545 (NO2), 1509, 1439, 1344
(NO2), 1238, 1180, 1025, 913, 821, 729 cmꢀ1. Anal. Calcd for
C15H12N4O5: C, 54.88; H, 3.68; N, 17.07. Found: C, 54.65; H, 4.04; N,
16.72.
4.6.2. 5-Benzylselanyl-1-butyl-1H-tetrazole (23). Yellowish viscous
oil. 1H NMR (300 MHz, CDCl3):
d 7.29e7.19 (5H, m), 4.51 (2H, s), 4.05
(2H, t, J¼7.2 Hz), 1.74e1.59 (2H, m), 1.14e1.26 (2H, m), 0.85 (3H, t,
J¼7.3 Hz); 13C NMR (75 MHz, CDCl3):
d 145.91, 136.72, 128.93,
4.5.12. (Z)-Se-(3,5-Dinitrobenzyl)-N-cyano-N,N0-di(4-
methoxyphenyl)isoselenourea (20c). Yellowish solid; mp 142 ꢁC
(with decomposition). Rf (hexane/EtOAc, 3:1) 0.29. 1H NMR
128.81, 127.92, 47.67, 32.91, 31.20, 19.46, 13.30. IR (KBr): 2960, 2873,
1495, 1454, 1426, 1381, 1183, 1070, 979, 760, 697 cmꢀ1. LRMS m/z
(ESI) 296.8 (100, MHþ), 294.8 (49), 292.9 (18%); HRMS m/z (ESI)
calcd for C12H16N4SeþHþ (MþHþ) 297.06129, found 297.06131.
(500 MHz, acetone):
d
8.80 (1H, t, J¼2.2 Hz), 8.48 (2H, d,
J¼2.2 Hz), 7.40 (2H, d, J¼9.0 Hz), 7.01 (2H, d, J¼9.0 Hz), 6.90e6.76
(4H, m), 4.32 (2H, s), 3.83 (3H, s), 3.76 (3H, s); 13C NMR (125 MHz,
4.6.3. 1-Butyl-5-(3,5-dinitrobenzylselanyl)-1H-tetrazole (24). White
acetone):
d
160.90, 158.05, 149.35, 144.26, 143.74, 141.20, 131.06,
solid; mp 89 ꢁC. 1H NMR (300 MHz, CDCl3):
d
8.92 (1H, t, J¼2.0 Hz),
129.91, 128.73, 122.76, 118.22, 115.68, 114.92, 111.56, 55.96, 55.64,
30.05. IR (KBr): 3112, 2904, 2221 (C^N), 1625, 1542 (NO2), 1505,
1342 (NO2), 1245, 1175, 1076, 1038, 833, 730 cmꢀ1; HRMS m/z
(ESI) calcd for C23H19N5O6SeþHþ (MþHþ) 542.05733, found
542.05739.
8.69 (2H, d, J¼2.1 Hz), 4.77 (2H, s), 4.20(2H, t, J¼7.2 Hz), 1.94e1.67 (2H,
m),1.40e1.15 (2H, m), 0.93 (3H, t, J¼7.3 Hz); 13C NMR (75MHz, CDCl3):
d
148.52,145.00,142.05,129.43,118.13, 47.97, 31.18, 29.66,19.54,13.31.
IR (KBr): 3103, 2965, 2877, 1537 (NO2), 1428, 1343 (NO2), 1194, 1075,
987, 915, 810, 731, 677 cmꢀ1. Anal. Calcd for C12H14N6O4Se: C, 37.41; H,
3.66; N, 21.82. Found: C, 37.5; H, 4.0; N, 21.75.
Compounds 21a, 21b, and 21c were separated by silica gel col-
umn chromatography, mobile phase: hexane/EtOAc, 8:1.
4.6.4. 5-Methylselanyl-1-hexyl-1H-tetrazole (25). Yellowish viscous
4.5.13. 1-(4-Bromphenyl)-5-(3,5-dinitrobenzylselanyl)-1H-tetrazole
oil. 1H NMR (300 MHz, CDCl3):
d
4.22 (2H, t, J¼7.2 Hz), 2.70 (3H, s),
1.94e1.79 (2H, m), 1.41e1.15 (6H, m), 0.94e0.79 (3H, m); 13C NMR
(75 MHz, CDCl3): 146.43, 47.96, 30.97, 29.12, 25.95, 22.33, 13.87,
(21a). White solid; mp 154e155 ꢁC (with decomposition). Rf
(hexane/EtOAc, 3:1) 0.12. 1H NMR (500 MHz, acetone)
d
8.84 (2H, d,
d
J¼2.1 Hz), 8.80 (1H, t, J¼2.1 Hz), 7.84 (2H, d, J¼8.8 Hz), 7.58 (2H, d,
8.12. IR (KBr): 2955, 2931, 2859, 2213 (w), 1457, 1427, 1382, 1275,
1180, 1082, 925, 728, 659 cmꢀ1. LRMS m/z (ESI) 248.8 (100, MHþ),
246.9 (52), 244.9 (21%); HRMS m/z (ESI) calcd for C8H16N4SeþHþ
(MþHþ) 249.06129, found 249.06131.
J¼8.3 Hz), 4.95 (2H, s); 13C NMR (125 MHz, acetone):
d 148.38,
146.76, 143.59, 133.19, 133.11, 129.57, 126.28, 123.99, 117.40, 29.71. IR
(KBr): 3104, 2923, 1530 (NO2), 1496, 1361, 1340 (NO2), 1176, 1073,
1007, 841, 731, 674 cmꢀ1. Anal. Calcd for C14H9BrN6O4Se: C, 34.73; H,
1.87; N, 17.36. Found: C, 34.93; H, 1.68; N, 17.01.
4.6.5. 5-Benzylselanyl-1-hexyl-1H-tetrazole (26). Yellowish viscous
oil. 1H NMR (300 MHz, CDCl3):
d 7.32e7.23 (5H, m), 4.55 (2H, s),
4.5.14. N-(4-Bromphenyl)-N-(3,5-dinitrobenzyl)cyanamide
4.08 (2H, t, J¼7.2 Hz), 1.78e1.68 (2H, m), 1.29e1.19 (6H, m), 0.86
(21b). Beige solid; mp 170 ꢁC (with decomposition). Rf (hexane/
(3H, t, J¼6.5 Hz); 13C NMR (75 MHz, CDCl3):
d 145.93, 136.71, 128.91,
EtOAc, 3:1) 0.18. 1H NMR (300 MHz, acetone):
d
8.92 (1H, t,
128.80, 127.92, 47.96, 32.89, 30.92, 29.20, 25, 87, 22.30, 13.87. IR
J¼2.2 Hz), 8.77 (2H, d, J¼2.1 Hz), 7.57 (2H, d, J¼9.1 Hz), 7.26 (2H, d,
(KBr): 2930, 2858,1495,1454,1426,1381,1178,1069, 760, 697 cmꢀ1
.
J¼9.1 Hz), 5.39 (2H, s); 13C NMR (75 MHz, acetone)
d
149.80, 140.53,
LRMS m/z (ESI) 324.8 (100, MHþ), 322.8 (52), 326.9 (19%); HRMS m/
139.92, 133.59, 128.99, 119.41, 118.95, 117.09, 113.21, 52.51. IR (KBr):
3149, 2959, 2230 (s, C^N), 1595, 1492, 1485, 1395, 1283, 1252, 1178,
1074,1010, 813 cmꢀ1. Anal. Calcd for C14H9BrN4O4: C, 44.58; H, 2.41;
N, 14.86. Found: C, 44.2; H, 2.71; N, 14.59.
z
(ESI) calcd for C14H20N4SeþHþ (MþHþ) 325.09260, found
325.09262.
4.6.6. 5-(3,5-Dinitrobenzylselanyl)-1-hexyl-1H-tetrazole
(27). White crystalline solid; mp 57e58 ꢁC. 1H NMR (500 MHz,
4.5.15. (Z)-Se-(3,5-Dinitrobenzyl)-N-cyano-N,N0-di(4-bromophenyl)
isoselenourea (21c). Beige solid; mp 156e158 ꢁC (with de-
composition). Rf (hexane/EtOAc, 3:1) 0.33. 1H NMR (300 MHz, ac-
acetone):
d
8.82e8.79 (3H, m), 4.89 (2H, s), 4.29 (2H, t, J¼7.1 Hz),
1.81e1.76 (2H, m), 1.25e1.20 (6H, m), 0.82 (3H, t, J¼7.0 Hz); 13C
NMR (125 MHz, acetone):
d 149.28, 146.43, 144.77, 130.30, 118.25,
etone):
d
8.82 (1H, t, J¼2.1 Hz), 8.58 (2H, d, J¼2.1 Hz), 7.68 (2H, d,
48.66, 31.67, 30.55, 30.32, 26.52, 22.96, 14.10. IR (KBr): 3111, 2933,
2859,1541 (NO2), 1460, 1426, 1385, 1343 (NO2), 1179, 1074, 809, 729,
675 cmꢀ1. Anal. Calcd for C14H18N6O4Se: C, 40.69; H, 4.39; N, 20.33.
Found: C, 41.01; H, 4.61; N, 20.14. LRMS m/z (ESI) 415.0 (100, MHþ),
413.1 (43), 416.9 (16%).
J¼8.8 Hz), 7.50 (2H, d, J¼8.8 Hz), 7.43 (2H, d, J¼8.6 Hz), 6.76 (2H, d,
J¼8.6 Hz), 4.52 (s, 2H); 13C NMR (75 MHz, acetone):
d 149.41,
147.57, 144.97, 144.03, 137.66, 133.68, 132.73, 129.95, 128.61, 123.53,
122.78, 118.37, 118.32, 110.95, 30.60. IR (KBr): 3101, 2923, 2234
(C^N), 1616, 1539 (NO2), 1487, 1344 (NO2), 1184, 1071, 1013, 913,
825, 730, 672 cmꢀ1. Anal. Calcd for C21H13Br2N5O4Se: C, 39.53; H,
2.05; N, 10.97. Found: C, 39.91; H, 2.43; N, 10.76; HRMS m/z (ESI)
4.6.7. 5-Methylselanyl-1-octyl-1H-tetrazole (28). Yellowish viscous
oil. 1H NMR (300 MHz, CDCl3):
d
4.23 (2H, t, J¼7.2 Hz), 2.72 (3H,

G. Karabanovich et al. / Tetrahedron 69 (2013) 8798e8808
8807
s), 1.93e1.84 (2H, m), 1.35e1.22 (10H, m), 0.91e0.84 (3H,
m); 13C NMR (75 MHz, CDCl3):
146.44, 47.99, 31.65, 29.19,
28.97, 28.82, 26.30, 22.57, 14.04, 8.14. IR (KBr): 2926, 2856,
1455, 1426, 1340 (NO2), 1277, 1193, 1175, 1083, 997, 913, 817, 802,
744, 712, 684 cmꢀ1. Anal. Calcd for C14H16N6O4Se: C, 40.89; H, 3.92;
N, 20.43. Found: C, 40.57; H, 4.17; N, 20.06.
d
2218, 1457, 1427, 1383, 1276, 1176, 1087, 975, 924, 724 cmꢀ1
.
LRMS m/z (ESI) 276.9 (100, MHþ), 274.8 (48), 273.9 (19%); HRMS
m/z (ESI) calcd for C10H20N4SeþHþ (MþHþ) 277.09260, found
277.09263.
Acknowledgements
This work was supported by the Grant Agency of Charles Uni-
versity (Project GAUK 55610/2010) and Charles University in Prague
(SVV 267 001).
4.6.8. 5-Benzylselanyl-1-octyl-1H-tetrazole (29). Yellowish viscous
oil. 1H NMR (300 MHz, CDCl3):
d 7.32e7.22 (5H, m), 4.55 (2H, s),
4.07 (2H, t, J¼7.3 Hz), 1.78e1.68 (2H, m), 1.31e1.16 (10H, m), 0.86
(3H, t, J¼6.7 Hz); 13C NMR (75 MHz, CDCl3):
d 145.90, 136.71, 128.91,
Supplementary data
128.80, 127.92, 47.94, 32.89, 31.61, 29.23, 28.91, 28.74, 26.21, 22.53,
14.01. IR (KBr): 2926, 2855, 1495, 1454, 1426, 1381, 1174, 760, 723,
697 cmꢀ1. LRMS m/z (ESI) 352.8 (100, MHþ), 350.9 (53), 354.8 (21%);
HRMS m/z (ESI) calcd for C16H24N4SeþHþ (MþHþ) 353.12390,
found 353.12386.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.07.103.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
4.6.9. 5-(3,5-Dinitrobenzylselanyl)-1-octyl-1H-tetrazole (30). White
References and notes
solid; mp 61e62 ꢁC. 1H NMR (300 MHz, CDCl3):
d 8.92 (1H, t,
J¼2.1 Hz), 8.69 (2H, d, J¼2.1 Hz), 4.76 (2H, s), 4.19 (2H, t,
1. Schwarz, K.; Foltz, C. J. Am. Chem. Soc. 1957, 79, 3292e3293.
2. Dodig, S.; Cepelak, I. Acta Pharm. 2004, 54, 261e276.
3. Koketsu, M.; Ishihara, H. Curr. Org. Chem. 2003, 7, 175e185.
4. Libero, F. M.; Xavier, M. C. D.; Victoria, F. N.; Nascente, P. S.; Savegnago, L.; Perin,
G.; Alves, D. Tetrahedron Lett. 2012, 53, 3091e3094.
5. Koketsu, M.; Tanaka, K.; Takenaka, Y.; Kwong, C. D.; Ishihara, H. Eur. J. Pharm.
Sci. 2002, 15, 307e310.
6. Parnham, M. J.; Graf, E. Prog. Drug Res. 1991, 36, 9e47.
J¼7.2 Hz), 1.88e1.76 (2H, m), 1.32e1.20 (10H, m), 0.90e0.83 (m,
3H); 13C NMR (75 MHz, CDCl3)
d 148.54, 144.97, 142.05,
129.40, 118.12, 48.23, 31.59, 29.66, 29.23, 28.91, 28.75, 26.27,
22.53, 14.01. IR (KBr): 3087, 2930, 2857, 1533 (NO2), 1450, 1430,
1344 (NO2), 1175, 1084, 931, 809,732, 676 cmꢀ1. Anal. Calcd for
C16H22N6O4Se: C, 43.54; H, 5.02; N, 19.04. Found: C, 43.58; H,
5.36; N, 19.07.
7. Koketsu, M.; Ishihara, H.; Wu, W. J.; Murakami, K.; Saiki, I. Eur. J. Pharm. Sci.
1999, 9, 157e161.
8. May, S. W.; Wang, L. Q.; GillWoznichak, M. M.; Browner, R. F.; Ogonowski, A. A.;
Smith, J. B.; Pollock, S. H. J. Pharm. Exp. Ther. 1997, 283, 470e477.
9. Roh, J.; Vavrova, K.; Hrabalek, A. Eur. J. Org. Chem. 2012, 6101e6118.
10. Myznikov, L. V.; Hrabalek, A.; Koldobskii, G. I. Khim. Geterotsikl. Soedin. 2007,
3e13.
11. Muraglia, E.; Kinzel, O. D.; Laufer, R.; Miller, M. D.; Moyer, G.; Munshi, V.; Or-
vieto, F.; Palumbi, M. C.; Pescatore, G.; Rowley, M.; Williarns, P. D.; Summa, V.
Bioorg. Med. Chem. Lett. 2006, 16, 2748e2752.
12. Adamec, J.; Waisser, K.; Kunes, J.; Kaustova, J. Arch. Pharm. 2005, 338, 385e389.
13. Adamec, J.; Beckert, R.; Weiss, D.; Klimesova, V.; Waisser, K.; Mollmann, U.;
Kaustova, J.; Buchta, V. Bioorg. Med. Chem. 2007, 15, 2898e2906.
14. Shin, K. J.; Koo, K. D.; Yoo, K. H.; Kim, D. C.; Kim, D. J.; Park, S. W. Bioorg. Med.
Chem. Lett. 2000, 10, 1421e1425.
4.6.10. 1-Cyclohexyl-5-methylselanyl-1H-tetrazole (31). Yellowish
viscous oil. 1H NMR (300 MHz, CDCl3):
d
4.20e4.07 (1H, m), 2.71
(3H, s), 2.10e1.87 (6H, m), 1.80e1.70 (1H, m), 1.54e1.19 (3H, m); 13C
NMR (75 MHz, CDCl3) 145.42, 58.85, 32.21, 25.14, 24.78, 7.99. IR
d
(KBr): 2935, 2857, 1452, 1423, 1383, 1366, 1272, 1189, 1083, 1001,
894, 817, 752 cmꢀ1. LRMS m/z (ESI) 246.9 (100, MHþ), 244.8 (52),
243.0 (20%); HRMS m/z (ESI) calcd for C8H14N4SeþHþ (MþHþ)
247.04564, found 247.04571.
15. Dhayanithi, V.; Syed, S. S.; Kumaran, K.; Sankar, K. R. J.; Ragavan, R. V.; Goud, P.
S. K.; Kumari, N. S.; Pati, H. N. J. Serb. Chem. Soc. 2011, 76, 165e175.
16. Disli, A.; Salman, M. Russ. J. Org. Chem. 2009, 45, 151e153.
17. Sureshbabu, V. V.; Vasantha, B.; Hemantha, H. P. Synthesis 2011, 1447e1455.
18. Kanakaraju, S.; Prasanna, B.; Chandramouli, G. V. P. J. Chem. Pharm. Res. 2012, 4,
2994e2998.
19. Koldobskii, G. I.; Kharbash, R. B. Russ. J. Org. Chem. 2003, 39, 453e470.
20. Yildirir, Y.; Us, M. F.; Colak, N.; Ozkan, H.; Yavuz, S.; Disli, A.; Ozturk, S.; Turker,
L. Med. Chem. Res. 2009, 18, 91e97.
4.6.11. 5-Benzylselanyl-1-cyclohexyl-1H-tetrazole (32). White solid;
mp 62 ꢁC. 1H NMR (300 MHz, CDCl3): 7.32e7.20 (5H, m), 4.53 (2H,
s), 4.08e3.97 (1H, m), 1.90e1.79 (6H, m), 1.71e1.67 (1H, m),
1.37e1.20 (3H, m); 13C NMR (75 MHz, CDCl3):
d 144.91, 136.79,
128.91, 128.77, 127.83, 58.81, 32.77, 32.23, 25.08, 24.73. IR (KBr):
2935, 2857, 1494, 1452, 1421, 1365, 1272, 1185, 1083, 1001, 894, 817,
753, 696 cmꢀ1. Anal. Calcd for C14H18N4Se: C, 52.34; H, 5.65; N,
17.44. Found: C, 52.27; H, 5.98; N,17.36. LRMS m/z (ESI) 322.97 (100,
MHþ), 321.0 (48), 319.01 (19%).
21. Bartelskeith, J. R.; Mahoney, J. B.; Puttick, A. J. J. Org. Chem. 1985, 50, 980e987.
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3725e3731.
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4.6.12. 1-Cyclohexyl-5-(3,5-dinitrobenzylselanyl)-1H-tetrazole
(33). Yellowish crystalline solid; mp 103 ꢁC. 1H NMR (500 MHz,
CDCl3):
4.13e4.04 (1H, m), 2.02e1.86 (6H, m), 1.77e1.74 (1H, m), 1.46e1.22
(3H, m); 13C NMR (125 MHz, CDCl3):
148.51, 143.93, 142.17,
d 8.94e8.90 (1H, m), 8.72e8.69 (2H, m), 4.77 (2H, s),
d
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129.44, 118.07, 59.27, 32.29, 29.48, 25.05, 24.67. IR (KBr): 3095,
2941, 2859, 1538 (NO2), 1452, 1424, 1383, 1361, 1342 (NO2), 1276,
1198, 1083, 1005, 922, 817, 808, 731, 671 cmꢀ1. Anal. Calcd for
C14H16N6O4Se: C, 40.89; H, 3.92; N, 20.43. Found: C, 40.93; H, 4.21;
N, 20.74.
30. Iwaoka, M.; Tomoda, S. Top. Curr. Chem. 2000, 208, 55e80.
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Seo, M. J.; Park, E. J.; Skovierova, H.; Pham, H.; Riccardi, G.; Nam, J. Y.; Marsollier,
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32. Makarov, V.; Manina, G.; Mikusova, K.; Mollmann, U.; Ryabova, O.; Saint-Joanis,
B.; Dhar, N.; Pasca, M. R.; Buroni, S.; Lucarelli, A. P.; Milano, A.; De Rossi, E.;
Belanova, M.; Bobovska, A.; Dianiskova, P.; Kordulakova, J.; Sala, C.; Fullam, E.;
Schneider, P.; McKinney, J. D.; Brodin, P.; Christophe, T.; Waddell, S.; Butcher, P.;
Albrethsen, J.; Rosenkrands, I.; Brosch, R.; Nandi, V.; Bharath, S.; Gaonkar, S.;
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4.6.13. 1-Cyclohexyl-5-(2,4-dinitrobenzylselanyl)-1H-tetrazole
(34). Yellowish crystalline solid; mp 98e99 ꢁC. 1H NMR (500 MHz,
CDCl3):
d
8.98 (1H, d, J¼2.3 Hz), 8.41 (1H, dd, J¼8.6, 2.3 Hz), 8.18 (1H,
d, J¼8.6 Hz), 4.94 (2H, s), 4.07e3.98 (1H, m), 2.01e1.85 (6H, m),
1.78e1.71 (1H, m), 1.46e1.20 (3H, m); 13C NMR (125 MHz, CDCl3):
d
147.44, 146.94, 145.12, 141.32, 134.33, 128.21, 121.08, 59.20, 32.22,
28.08, 25.04, 24.68. IR (KBr): 3089, 2955, 2853, 1611, 1537 (NO2),

8808
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