Fast preparation of benzofuroxans by microwave-assisted pyrolysis of o-nitrophenyl azides

Article abstract of DOI:10.1016/j.mencom.2013.07.013

Microwave-assisted pyrolysis of o-nitrophenyl azides gives benzofuroxans in good yields in short reaction times.

Full text of DOI:10.1016/j.mencom.2013.07.013

Mendeleev
Communications
Mendeleev Commun., 2013, 23, 217–218
Fast preparation of benzofuroxans by microwave-
assisted pyrolysis of o-nitrophenyl azides
Elisa Leyva,* Socorro Leyva, Regina M. González-Balderas,
Denisse de Loera and Rogelio Jiménez-Cataño
Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P. México 78290.
E-mail: elisa@uaslp.mx
DOI: 10.1016/j.mencom.2013.07.013
Microwave-assisted pyrolysis of o-nitrophenyl azides gives benzofuroxans in good yields in short reaction times.
O
Benzofuroxans (benzo-2,1,3-oxadiazole N-oxides) are important
heterocyclic compounds with diverse biological activity. They
R3
R2
R3
R2
1
NO2
N
hv, or MW
N2
have gained interest as cardiovascular agents since they generate
nitric oxide which plays an important role as a biological mes-
O
–
N
N3
2
R1
R1
senger. They have been extensively investigated as calcium
3
1
4
channel modulators, herbicides and energetic materials.
1
a–i
2a–i
In organic synthesis, benzofuroxans have been used for
the preparation of many pharmaceutical compounds like benz-
Scheme 1
5
imidazole-3-oxides. They react very easily with carbonyl com-
5
these assertions.13 To induce this reaction, an aryl azide is usually
refluxed for several hours at high temperature (100–160°C) in
toluene, xylene, DMSO or acetic acid. The principal drawback of
pounds in basic media to give quinoxaline-1,4-dioxides. Benzo-
furoxans bearing electron-withdrawing substituents (fluoro, chloro
or nitro) are highly reactive and they have been applied in the
synthesis of a variety of heterocyclic compounds.5
10
this method is the long reaction time.
S
everal methods to prepare benzofuroxans have been reported.6,7
The application of microwave irradiation (MW) as a non-
o-Nitroaryl azides are the suitable precursors for heterocycliza-
conventional energy source for reactions has become a very
14
tion synthesis of benzofuroxans (Scheme 1) by photolysis or
popular and useful technique in organic chemistry. In general,
the use of MW energy leads to enhanced conversion rates, higher
yields, easier work up and cleaner reactions demonstrating the
real advantages of this methodology. In this paper, we report the
preparation of benzofuroxans by microwave-assisted pyrolysis of
o-nitrophenyl azides 1a–i (Scheme 1). This procedure represents
a fast methodology to prepare benzofuroxans.
At first, we performed the pyrolysis under conventional con-
ditions and refluxed the corresponding o-nitrophenyl azides 1a–i
at 110°C in acetic acid for 6 to 10 h (Table 1). Under these
conditions, we obtained the corresponding benzofuroxans 2b–i
in reasonable yields. However, benzofuroxan 2a was obtained in
moderate yield (50%). In this case, TLC analysis of the reaction
mixture indicated the presence of several by-products.
8
–10
pyrolysis.
Fluid phase photolysis of o-nitrophenyl azides produces benzo-
furoxans only in moderate yields (30–35%), while photolysis
in the crystalline state affords the corresponding heterocyclic
compounds in quantitative yields.10 However, this latter method
provides good yields only in cases of crystalline substrates having
a high melting point above 50°C because the reaction proceeds
under topotactic control due to the proximity of reacting groups
11
NO and N in the crystal.
2
3
Thermal cyclization of o-nitrophenyl azides is most widely
used in the preparation of benzofuroxans.10 It has been proposed
that an ortho-nitro substituent participates in a pericyclic process
with little nitrene character.12 The computational studies support
Table 1 Preparation of benzofuroxans 2a–i from o-nitrophenyl azides 1a–i.
Traditional pyrolysisa
Microwave pyrolysisb
Product
R1
R2
R3
Mp/°C
Time/h
Yield (%)
Time/min
Yield (%)
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
g
h
i
H
H
H
6
6
50
85
81
82
65
67
91
65
75
10
15
15
15
10
10
10
15
10
65
80
80
80
60
65
90
60
70
68–7115
84–8616
96–9716
96–9716
116–11716
47–4816
130–13117
141–14317
71–7218
Me
H
H
H
Me
H
H
6
H
Me
OMe
Cl
6
H
H
6
H
H
6
H
Cl
H
Cl
6
NO2
H
H
10
6
H
NO2
aA solution of o-nitrophenyl azide (150 mg) in acetic acid (20 ml) was refluxed. bA solution of o-nitrophenyl azide (150 mg) in DMSO (5 ml) and H O
2
(
1 ml) was irradiated in a microwave reactor (Discover CEM) at 120°C (100 W). The reaction mixture was poured into ice-water. Each product was
recrystallized from ethanol and characterized by UV-VIS, IR, Raman spectroscopy and mass spectrometry.
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2013 Mendeleev Communications. All rights reserved.
– 217 –

Mendeleev Commun., 2013, 23, 217–218
In order to choose an appropriate solvent, pyrolysis of o-nitro-
phenyl azide 1b was investigated under microwave irradiation
S. A. Shevelev, Mendeleev Commun., 2010, 20, 165; (g) O.Yu. Smirnov,
A. Yu. Tyurin, A. M. Churakov, Yu. A. Strelenko and V. A. Tartakovsky,
Russ. Chem. Bull., Int. Ed., 2006, 55, 137 (Izv. Akad. Nauk, Ser. Khim.,
(
100 W) at 120°C for 20 min using AcOH, DMF/H O and
2
2
006, 133); (h) A. Yu. Tyurin, O. Yu. Smirnov, A. M. Churakov, Yu. A.
Strelenko and V. A. Tartakovsky, Russ. Chem. Bull., Int. Ed., 2006,
5, 351 (Izv. Akad. Nauk, Ser. Khim., 2006, 341); (i) S. K. Kotovskaya,
D
MSO/H O as solvents. The crude product mixtures were
2
analyzed by TLC, which indicated that the reaction proceeded
5
only in DMSO/H O. The microwave-assisted pyrolysis of o-nitro-
2
S. A. Romanova, V. N. Charushin and M. I. Kodess, Russ. J. Org. Chem.,
2004, 40, 1167 (Zh. Org. Khim., 2004, 40, 1214); (j) V. A. Voronina,
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phenyl azides 1a–i provided the corresponding crystalline benzo-
furoxans 2a–i in reasonable yields (Table 1).
1
384 (Zh. Org. Khim., 2004, 40, 1431); (k) I. V. Galkina, E. V. Tudrii,
The starting o-nitrophenyl azides were prepared following the
E. A. Berdnikov, L. M. Yusupova, F. S. Levinson, D. B. Krivolapov,
I. A. Litvinov, R. A. Cherkasov and V. I. Galkin, Russ. J. Org. Chem.,
2012, 48, 721 (Zh. Org. Khim., 2012, 48, 722).
procedure previously reported by us.10 An amount of each azide
1
a–i in DMSO/H O was irradiated (100 W) in a microwave
2
reactor at 120°C for several minutes. The microwave method
accelerated the synthesis of benzofuroxans 2a–i and also gave
purer crystalline products. The isolated yields of products were
comparable with those obtained by conventional refluxing (see
Table 1). Substrates bearing electron-withdrawing and electron-
donating substituents showed good reactivity.
6
7
A. B. Sheremetev, N. S. Aleksandrova, N. V. Ignat’ev and M. Schulte,
Mendeleev Commun., 2012, 22, 95.
G. Nikonov and S. Bobrov, in Comprehensive Heterocyclic Chemistry III,
eds. A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven and R. J. K. Taylor,
Elsevier, Amsterdam, London, 2008.
(a) G. Smolinski, J. Org. Chem., 1961, 26, 4108; (b) C. Wentrup, Adv.
Heterocycl. Chem., 1981, 28, 279.
8
9
In conclusion, microwave-assisted pyrolysis of o-nitrophenyl
A. R. Katritzky and M. F. Gordeev, Heterocycles, 1993, 35, 483 and
references therein.
azides in DMSO/H O represents a versatile, fast and cleaner
2
technique to prepare benzofuroxans.
10 (a) S. Leyva, V. Castanedo and E. Leyva, J. Fluorine Chem., 2003, 121,
1
71; (b) E. Leyva, D. de Loera and R. Jiménez-Cataño, Tetrahedron Lett.,
2
010, 51, 3978; (c) E. Leyva, R. M. González-Balderas, D. de Loera and
This work was supported by CONACyT (grant no. CB-2010-
5678). R.M.G.-B. acknowledges financial support by CONACyT
scholarship no. 290618) for an intership at UCLA.
R. Jimenez-Cataño, Tetrahedron Lett., 2012, 53, 2447; (d) D. de Loera
Carrera, E. Leyva and R. Jiménez Cataño, Bol. Soc. Quím. Méx., 2009,
3
1
(
5
, 93; (e) E. Leyva, D. de Loera, S. Leyva and R. Jiménez-Cataño, in
Nitrene and Nitrenium Ions, eds. D. E. Falvey andA. D. Gudmundsdottir,
John Wiley & Sons, Inc., New York, 2013.
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Received: 15th January 2013; Com. 13/4046
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