Synthesis of azido arylselenides and azido aryldiselenides: a new class of selenium-nitrogen compounds

Article abstract of DOI:10.1016/j.tetlet.2010.04.076

We present here our results of the efficient synthesis of azido arylselenides and azido aryldiselenides under mild conditions. Starting from nitrogen-substituted benzenes, we incorporated selenium atom at aromatic ring and obtained amino arylselenides and diselenides in satisfactory yields. Treatment of these compounds with iso-pentyl nitrite (i-C₅H₁₁ONO) and azido trimethylsilane (Me₃SiN₃) in THF affords a variety of azido arylselenides and diselenides in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2010.04.076

Tetrahedron Letters 51 (2010) 3364–3367
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of azido arylselenides and azido aryldiselenides: a new class
of selenium–nitrogen compounds
Anna Maria Deobald a, Leandro R. Simon de Camargo a, Greice Tabarelli c, Manfredo Hörner a,
Oscar E. D. Rodrigues a, Diego Alves b, Antônio L. Braga c,
*
a Universidade Federal de Santa Maria, Departamento de Química, CEP 97105-900, Camobi, Santa Maria, RS, Brazil
b Universidade Federal de Pelotas, Departamento de Química Orgânica, CEP 96010-900, Pelotas, RS, Brazil
c Universidade Federal de Santa Catarina, UFSC - Departamento de Química, CEP 88040-900, Florianópolis, SC, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
We present here our results of the efficient synthesis of azido arylselenides and azido aryldiselenides
under mild conditions. Starting from nitrogen-substituted benzenes, we incorporated selenium atom
at aromatic ring and obtained amino arylselenides and diselenides in satisfactory yields. Treatment of
these compounds with iso-pentyl nitrite (i-C5H11ONO) and azido trimethylsilane (Me3SiN3) in THF affords
a variety of azido arylselenides and diselenides in good to excellent yields.
Received 7 February 2010
Revised 18 April 2010
Accepted 19 April 2010
Available online 24 April 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Organoselenium compounds become attractive synthetic tar-
gets because of their chemo-, regio-, and stereoselective reactions1
used in organic catalysis2 and useful biological activities.3 Many
classes of organoselenium compounds have been prepared and
studied to date mainly due their usefulness in organic synthesis.4
Selenides or diselenides containing nitrogen atom in their struc-
ture are a special class of these compounds and have been em-
ployed in various organic transformations such as asymmetric
synthesis.1,2,4
In this context, Tiecco et al. described asymmetric azido selen-
enylation of alkenes to obtain enriched nitrogen-containing com-
pounds.5 Additionally, these research group and others have
published a great number of synthesis of azido-selenium com-
pounds.6 These compounds have a larger synthetic importance
since they combine the well-known reactivity of the azido group
with the selenium moiety.7
give a variety of five-membered nitrogen heterocycles.13 This has
motivated a demand for readily accessible azide building blocks,
and consequently, a need for efficient methods for installing this
functional group.
However, the synthesis of aryl azides relies upon a more limited
selection of transformations which may sometimes be problematic
with respect to the presence of incompatible functional groups.8
Recently, Mose and co-workers reported a new approach in the
synthesis of aromatic azides from the corresponding amines under
mild reaction conditions. This methodology offers advantages over
typical procedures in terms of safety, ease of execution, and
efficiency.14
To the best of our knowledge, no reactions to obtain azidoaryl-
selenides or azidoaryldiselenides were described so far. Our
Since the synthesis of the first organic azide, namely phenyl
azide, these energy-rich and flexible intermediates have attracted
significant attention in organic and bioorganic chemistries.8 The
organic azides received considerable attention in the last century
with applications in the chemistry of the acyl, aryl, and alkyl
azides.8 In principle, organic azides may be prepared according to
five different methods:8 (a) substitution or addition of N3 group;
(b) insertion of an N2 group; (c) diazotization; (d) cleavage of triaz-
ides and analogous compounds; and (e) rearrangement of azides.
Because of their relatively high stability, organic azides9 were used
in combinatorial drug discovery,10 material science,11 and biocon-
jugation.12 Recently, a major application of this class of compounds
is the 1,3-dipolar cycloaddition with an unsaturated reactant to
X
ArSe
or
Se Se
R
N3
N3
N3
R = NO2, NH2
X = Cl, I
Scheme 1.
NaBH4/EtOH
DMSO
Zn / NH4Cl
THF
SePh
SePh
NH2
PhSeSePh
Cl
NO2
1a
2a
84%
NO2
* Corresponding author. Tel.: +55 48 37216844; fax: +55 48 37216850.
E-mail address: albraga@qmc.ufsc.br (A.L. Braga).
Scheme 2.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.076

A. M. Deobald et al. / Tetrahedron Letters 51 (2010) 3364–3367
3365
Table 1
continuing interest in the synthesis of selenium-containing nitro-
gen compounds2 prompted us to explore a general procedure to
obtain azidoarylselenides and azidoaryldiselenides starting from
nitrogen-substituted benzenes (Scheme 1).
Synthesis of amino arylchalcogeno compounds 2a–l18,19
NaBH4/EtOH
DMSO
Zn / NH4Cl
THF
SeAr
SeAr
NH2
ArSeSeAr
Cl
Our initial studies have focused on the synthesis of amino
arylselenides and diselenides, key intermediates for the synthesis
of desired azido-selenium compounds. Thus, a mixture of diphe-
nyl diselenide and NaBH4 in EtOH was treated with 2-chloronitro-
benzene in DMSO15 and refluxed for 12 h giving rise to nitro-
arylselenide 1a quantitatively, which could be used directly for
the next step without further purification. Reduction of nitro
compound 1a with Zn/NH4Cl in THF16 affords amino arylselenide
2a in 84% yield (Scheme 2). A variety of diaryl diselenides and
nitroaryl compounds were converted to the corresponding amino
arylselenides and satisfactory results were obtained under this
protocol (Table 1).
For the synthesis of amino aryldiselenides, other protocol was
used. Starting from 2-iodoaniline in THF, treatment with n-BuLi,
further trapping of lithium anion with elemental selenium and fer-
rocyanide oxidation,17 affords the corresponding amino aryldisele-
nide 2m in good yield. This protocol was extended to obtain
tellurium analogue and the corresponding amino arylditelluride
2n was synthesized in satisfactory yield (Scheme 3).
Next, we turned our attention to the synthesis of azido-sele-
nium compounds. We chose compound 2a, iso-pentyl nitrite
(i-C5H11ONO), and sodium azide (NaN3) as standard substrates to
improve the reaction conditions. Optimization studies were carried
out to access 3a, which was formed in poor yields when reactions
were performed using DMF, THF, and CH3CN as solvent. To our sat-
isfaction, the reaction proceeds smoothly and rapidly in THF by
using azido trimethylsilane (TMSN3) as azide source. In an opti-
mized reaction (Scheme 4), amino arylselenide 2a (1 equiv) was
NO2
NO2
Entry
1
Product
Total yielda (%)
Se
84
NH2
2a
OMe
2
3
4
75
68
60
Se
Se
NH2
2b
Me
Cl
NH2
2c
Se
2d
NH2
NH2
NH2
NH2
Se
5
6
7
71
65
58
OMe
Me
Cl
2e
1) n-BuLi
THF, -78 oC, 1 h
Se
I
2) Yo, r.t., 1 h
Y Y
2f
3) K3Fe(CN)6 aq.
NH2
NH2
NH2
Y - Se = 2m, 88%
Y - Te = 2n, 50%
Se
Scheme 3.
2g
Me
Me
1) i-C5H11ONO
THF, 0 oC
SePh
NH2
SePh
N3
8
45
Se
NH2
Me
Se
2) TMSN3
0 o
C
r.t.
2h
2a
1h
3a
99%
9
40
79
H2N
Scheme 4.
2i
2j
H2N
10
Se
Se
H2N
11
12
75
72
NH2
2k
S
NH2
2l
a
Yields are given for isolated products.
Figure 1. Molecular structure of 3a by X-ray analysis.

3366
A. M. Deobald et al. / Tetrahedron Letters 51 (2010) 3364–3367
Table 2
Table 2 (continued)
Synthesis of azido arylchalcogeno compounds 3a–m20
Entry
10
Starting material
Product
Yielda (%)
1) i-C5H11ONO
SeAr
H2N
N3
SeAr
N3
THF, 0 oC
2) TMSN3
NH2
40
Se
Se
0 o
C
r.t.
NH2
2k
N3
1h
3j
Entry
1
Starting material
Product
Yielda (%)
S
S
11
12
13
90
71
50
NH2
N3
Se
Se
99
2l
3k
N3
NH2
2a
3a
OMe
Me
Cl
OMe
Se Se
Se Se
NH2
NH2
N3
N3
2m
3l
Se
2
3
95
96
Se
N3
NH2
3b
2b
Te Te
Te Te
Me
NH2
NH2
N3
N3
2n
3m
Se
Se
a
Yields are given for isolated products.
N3
NH2
3c
2c
Cl
dissolved in THF and reacted in the presence of i-C5H11ONO
(1.55 equiv) and TMSN3 (1.2 equiv) at 0 °C, with warming to room
temperature, to yield compound 3a in 99%.
The molecular structure of the product 3a could be verified by
X-ray analysis of a suitable single crystal leading unequivocally
to the azido arylselenide 3a (Fig. 1).
Se
Se
NH2
4
5
6
7
88
95
99
80
N3
3d
2d
In order to demonstrate the efficiency of this protocol, a variety
of substituted amino arylselenides were converted to the corre-
sponding azido arylselenides and the results are summarized in Ta-
ble 2. Inspection of Table 2 shows that the reaction worked well for
a variety of amino arylselenides. A closer inspection of the results
revealed that the reaction is slightly sensitive to electronic effects.
For example, the presence of electron-donating groups on the
arylseleno moiety gave the best yields of products (Table 2; entries
2–3 and 5–6). Electron-withdrawing groups in the arylseleno moi-
ety promote a decrease in the yields of the desired products (Table
2; entries 4 and 7).
Compound 2h, a hindered amine, was converted to the corre-
sponding azido-selenium compound in 75% yield (Table 2; entry
8). Amino arylsulfide 2l was efficiently reacted in these conditions
and azido arylsulfide 3k was formed in excellent yield (Table 2;
entry 11). Notably, when amino aryldiselenide 2m and amino
arylditelluride 2n were used, the corresponding products 3l and
3m were obtained in satisfactory yields (Table 2; entries 12 and
13).
Se
Se
NH2
NH2
NH2
OMe
N3
N3
N3
OMe
Me
Cl
2e
3e
Se
Se
Me
2f
3f
Se
Se
Cl
2g
3g
Me
Me
Me
Me
In summary, we have successfully prepared a new class of sele-
nium–nitrogen compounds: azido arylselenides and azido aryldi-
selenides. The synthesis proceeds under mild conditions, starting
from nitrogen-substituted benzenes, and the azido-selenium com-
pounds were obtained in good to excellent yields. Applications of
this class of azido-selenium compounds are ongoing in our
laboratory.
Se
8
9
75
75
Se
N3
Me
NH2
Me
Se
3h
2h
H2N
N3
Se
Acknowledgment
2j
3i
We are obliged to CNPq (INCT-Catálise, INCT_NANOBIOSIMES).

A. M. Deobald et al. / Tetrahedron Letters 51 (2010) 3364–3367
3367
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References and notes
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18. General procedure for the synthesis of nitro-arylselenides: To
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appropriate diaryl diselenide (5 mmol) in ethanol (25 mL) NaBH4 (10.9 mmol,
0.413 g) was added in three portions under argon. The solution was stirred
until it changed to a colorless solution, then appropriate chloro-nitrobenzene
(9.2 mmol, 1.449 g) in 2 mL of DMSO was added slowly. The mixture was
stirred at a mild reflux for 12 h. After that, the solvent was removed under
vacuum, water (20 mL) was added, and the mixture was extracted with
dichloro methane. The organic layer was dried with MgSO4, concentrated
under vacuum, and the crude product was used in the next step.
5. Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.; Marini, F.; Bagnoli, L.;
Temperini, A. Angew. Chem., Int. Ed. 2003, 42, 3131.
19. General procedure for the synthesis of aminoarylselenides: The suspension of
nitro-arylselenide (5 mmol), zinc powder (75.4 mmol, 4.935 g), and
ammonium chloride (47.9 mmol, 2.565 g) in THF (38 mL) was refluxed for
20 h under argon atmosphere. The resulting suspension was filtered washing
the solid residue with dichloro methane. The organic layer was dried with
MgSO4, concentrated under vacuum, and the product was isolated by column
chromatography using hexane/ethyl acetate as eluent. Selected spectral and
analytical data for compound 2a: Yield: 84%; yellow oil; IR (KBr) 3462,
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Bagnoli, L.; Temperini, A. Tetrahedron 2007, 63, 12373; (b) Tingoli, M.; Tiecco,
M.; Chianelli, D.; Balducci, R.; Temperini, A. J. Org. Chem. 1991, 56, 6809; (c)
Tiecco, M.; Testaferri, L.; Temperini, A.; Bagnoli, L.; Marini, F.; Santi, C. Synth.
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Moses, J. E. J. Am. Chem. Soc. 2006, 128, 15972; (b) Lee, L. V.; Mitchell, M. L.;
Huang, S.-J.; Fokin, V. V.; Sharpless, K. B.; Wong, C.-H. J. Am. Chem. Soc. 2003,
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3363 cmÀ1 1H NMR (CDCl3, 400 MHz) d = 7.48 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H),
;
7.16–7.06 (m, 6H), 6.69 (d, J = 7.6 Hz, 1H), 6.61 (t, J = 7.6 Hz, 1H), 4.17 (s, 2H);
13C NMR (CDCl3, 100 MHz) d = 148.52, 138.47, 130.97, 129.30, 129.18, 127.54,
126.12, 118.74, 114.95, 112.69. HRMS calcd for C12H11NSe: 249.0057. Found:
250.0141.
20. General procedure for the synthesis of azidoarylselenides: To
a solution of
aminoarylselenide or aminoaryldiselenide (1 mmol) in THF (1.5 mL), iso-
pentyl nitrite (1.55 mmol, 0.21 mL) followed by TMSN3 (1.2 mmol, 0.16 mL)
was added drop by drop at 0 °C under air. Then the mixture was stirred at
0 °C for 10 min, the ice bath was removed, and the mixture was stirred at
room temperature for 0.5–1 h. The solvent was removed under vacuum and
the product was isolated by column chromatography using hexane or
hexane/ethyl acetate as eluent. Selected spectral and analytical data for
compound 3a: Yield: 99%; yellow solid; mp 49.8–50.4 °C; IR (KBr) 2130 cmÀ1
;
1H NMR (CDCl3, 400 MHz) d = 7.56–7.53 (m, 2H), 7.35–7.30 (m, 3H), 7.23 (td,
11. (a) Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.; Voit, B.; Pyun,
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Am. Chem. Soc. 2003, 125, 3192; (b) Speers, A. E.; Cravatt, B. F. Chem. Biol. 2004,
11, 535.
J
1 = 8.0 Hz,
1 = 8.0 Hz,
J
2 = 1.2 Hz, 1H), 7.12 (dd,
2 = 1.2 Hz, 1H), 6.94 (td,
J
1 = 8.0 Hz, 2 = 1.2 Hz, 1H), 7.02 (dd,
J
1 = 8.0 Hz, 2 = 1.2 Hz, 1H); 13C NMR
J
J
J
J
(CDCl3, 100 MHz) d = 138.83, 135.10, 131.86, 129.56, 128.30, 128.25, 127.88,
125.52, 124.57, 118.17. HRMS calcd for C12H9N3Se: 274.9962. Found:
274.9970.