A fast and efficient method for the preparation of aryl azides using stable aryl diazonium silica sulfates under mild conditions

Article abstract of DOI:10.1016/j.tetlet.2009.05.049

An efficient, fast, and straightforward procedure for the synthesis of aromatic azides using aryl diazonium silica sulfates and sodium azide at room temperature under mild conditions is described. The use of inexpensive materials, simple and clean work-up

Full text of DOI:10.1016/j.tetlet.2009.05.049

Tetrahedron Letters 50 (2009) 4443–4445
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Tetrahedron Letters
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A fast and efficient method for the preparation of aryl azides using stable
aryl diazonium silica sulfates under mild conditions
Amin Zarei a,b, , Abdol R. Hajipour b,c, Leila Khazdooz d, Hamidreza Aghaei e
*
a Department of Science, Islamic Azad University, Fasa Branch, PO Box No. 364, Fasa 7461713591, Fars, Iran
b Pharmaceutical Research Laboratory, College of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
c Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison 53706-1532, WI, USA
d Department of Science, Islamic Azad University, Khorasgan Branch, Isfahan, 81595-158, Iran
e Department of Chemistry, Islamic Azad University, Shahreza Branch, Shahreza, 311-86145, Isfahan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient, fast, and straightforward procedure for the synthesis of aromatic azides using aryl diazonium
silica sulfates and sodium azide at room temperature under mild conditions is described. The use of inex-
pensive materials, simple and clean work-up, short reaction times and good yields are advantages of this
method.
Received 8 March 2009
Revised 3 May 2009
Accepted 15 May 2009
Available online 22 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Aryl diazonium silica sulfates
Sodium azide
Aryl azides
Aryl azides are versatile intermediates with various applica-
tions in organic and bioorganic chemistry.1 A major application
of these compounds is 1,3-dipolar cycloaddition to produce five-
membered heterocycles.2 In addition, aromatic azides are well
known for their use as photoaffinity labeling agents for proteins.3
Typically, these compounds are prepared from aromatic amines
with nitrous acid followed by addition of sodium azide at low tem-
perature.1a,4 Aryl azides have also been prepared by reaction of
arylmagnesium halides or aryllithium reagents with para-toluene-
sulfonyl azide.5 The above-mentioned conversion has also been
accomplished under mild conditions using a combination of aryl
amine, TfN3, CuSO4, and triethylamine.6 Direct coupling of aryl ha-
lides7 or aryl boronic acids8 with sodium azide catalyzed by copper
salts has been reported. These compounds have also been synthe-
sized from aromatic amines with t-BuONO followed by addition of
NaN39 or TMSN310 under mild conditions. Furthermore, [ArN2][BF4]
salts immobilized in [Bmim][PF6] ionic liquid with TMSN3 have
been reported for the preparation of aryl azides.11 Although some
of these methods utilize convenient protocols with good yields,
some of them suffer from disadvantages such as long reaction
times, low yields, and high temperatures leading to decomposition
of the aryl azides, poor stability of the reagents, use of toxic sol-
vents, and high costs.
In continuation of our studies on the stabilization of diazonium
salts on silica sulfuric acid and their applications in organic synthe-
sis,12 we report herein an efficient, fast, and convenient procedure
for the synthesis of aryl azides employing aryl diazonium silica sul-
fates in the presence of sodium azide at room temperature
(Scheme 1).
Diazonium salts are versatile compounds in organic chemistry.
However, their poor thermal stability limits their applications.
Usually these compounds are synthesized at around 10 °C, and to
avoid their decomposition, they are handled below 0 °C. In our pre-
vious work,12 we reported an efficient, fast, and convenient meth-
od for the preparation of aryldiazonium salts supported on the
surface of silica sulfuric acid13 (aryldiazonium silica sulfates). We
found that these aryldiazonium salts, ArNþ2 ꢀOSO3 ꢀ SiO2, were suf-
ficiently stable and could be kept at room temperature under anhy-
drous conditions.12 For example, 4-nitrophenyl diazonium silica
sulfate, which had been stored in a desiccator at room temperature
for three days, reacted with sodium azide in H2O and provided al-
most the same yield of 1-azido-4-nitrobenzene as that prepared
from fresh 4-nitrophenyl diazonium silica sulfate (Table 1, entry
12). To illustrate the scope of the present method, a range of aro-
matic amines were rapidly converted into the corresponding aryl
NaN3, H2O
r.t., 10-15 min
ArN3
ArN2 OSO3-SiO2
* Corresponding author. Tel.: +98 9171302528; fax: +98 3113912661.
E-mail address: aj_zarei@yahoo.com (A. Zarei).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.049

4444
A. Zarei et al. / Tetrahedron Letters 50 (2009) 4443–4445
Table 1
Conversion of aryl amines into the corresponding aryl azides using aryldiazonium silica sulfates at room temperaturea
Entry
Substrate
Time (min)
Product
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
C6H5NH2
10
10
10
15
10
10
10
15
15
10
10
10
15
10
C6H5N3
77
80
78
81
83
82
84
90
84
86
85
82
78
83
4-MeC6H4NH2
4-MeOC6H4NH2
4-PhC6H4NH2
4-ClC6H4NH2
4-MeC6H4N3
4-MeOC6H4N3
4-PhC6H4N3
4-ClC6H4N3
3-ClC6H4N3
4-BrC6H4N3
4-N3C6H4COOH
2-N3C6H4COOH
4-MeCOC6H4N3
4-NCC6H4N3
4-O2NC6H4N3
2-O2NC6H4N3
3-O2NC6H4N3
3-ClC6H4NH2
4-BrC6H4NH2
4-H2NC6H4COOH
2-H2NC6H4COOH
4-MeCOC6H4NH2
4-NCC6H4NH2
4-O2NC6H4NH2
2-O2NC6H4NH2
3-O2NC6H4NH2
N3
NH2
15
16
10
15
65
85
N
N
O
NH2
O
N3
O
O
O
O
17
18
15
15
15
87
76
88
N3
NH
2
N3
NH2
O
O
O
O
19
H3C
NH2
H3C
N3
a
Yield refers to isolated pure products which were characterized from their spectral data and by comparison with authentic samples.6–11,15,18
azides in good to high yields under mild conditions (Table 1).14,15
Acknowledgments
In contrast to related methods, aromatic amines with electron-
withdrawing groups or electron-donating groups also reacted.
The steric effects of ortho-substituents had relatively little influ-
ence on the reaction time and yields (Table 1, entries 9, 13, and
16). The corresponding phenol derivatives were formed in trace
yields as by-products. The crude products were obtained by filtra-
tion and work-up, and if necessary, were purified by short column
chromatography. In contrast to conventional methods, the reaction
rate increases on supporting the aryldiazonium salt on silica sulfu-
ric acid, as the surface area for reaction increases.12,16 Finally, after
completion of the reaction and isolation of the product, the solid
support could be recycled.12 In addition, the present procedure
for the preparation of aryldiazonium silica sulfates and aryl azides
is safe and non-explosive because by supporting aryldiazonium
salts on the surface of silica sulfuric acid as a bulky support, the
stability of these salts increases.12,17
We gratefully acknowledge the funding support received for
this project from the Islamic Azad University of Fasa and the Isfa-
han University of Technology (IUT).
References and notes
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In summary, we have developed an efficient, rapid, experimen-
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tion of aryl azides using aryldiazonium silica sulfates. These
reactions proceed at room temperature under mild conditions in
high yields. Further investigations on new applications of this
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A. Zarei et al. / Tetrahedron Letters 50 (2009) 4443–4445
4445
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H2O (3 mL), freshly prepared 4-bromophenyldiazonium silica sulfate (1 mmol)
was added gradually and the reaction mixture was stirred at rt for 10 min. The
mixture was diluted with EtOAc (15 mL) and was filtered after vigorous
stirring. The residue was extracted with EtOAc (3 ꢁ 12 mL) and the combined
organic layer was washed with 5% NaOH solution (12 mL) and then dried over
anhydrous Na2SO4. The solvent was evaporated to afford 1-azido-4-
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solid; mp 80–82 °C; 1H NMR (400 MHz, CDCl3) d 7.83 (2H, d, J = 8.8 Hz), 7.69
(2H, d, J = 8.0 Hz), 7.30 (2 H, d, J = 8.0 Hz), 7.12 (2 H, d, J = 8.8 Hz), 2.45 (3 H, s).
13C NMR (100 MHz, CDCl3) d 195.06, 144.19, 143.27, 134.85, 134.40, 132.00,
130.12, 129.06, 118.72, 21.68. IR (KBr) cmꢀ1: 3025, 2923, 2129, 2089, 1642,
1597, 1496, 1412, 1306, 1286, 1178, 1115, 929, 851, 826, 752. Anal. Calcd for
C14H11N3O: C, 70.88; H, 4.64; N, 17.72. Found: C, 70.75; H, 4.75; N, 17.63.
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14. General procedure for the preparation of aryl diazonium silica sulfate: An aromatic
amine (1 mmol), silica sulfuric acid (0.70 g),13e,f and sodium nitrite (2 mmol)
were ground in
a mortar with a pestle for a few minutes to afford a
homogeneous mixture. Then, a few drops of water were added gradually and
the reaction mixture was ground for 10–15 min to give the corresponding aryl
diazonium silica sulfate. Typical procedure for the preparation of 1-azido-4-
bromobenzene: To a stirring solution of sodium azide (2.5 mmol, 0.163 g) in