Nano indium oxide as a recyclable catalyst for the synthesis of arylaminotetrazoles

Article abstract of DOI:10.1007/s12039-012-0348-8

Nano indium oxide is an effective heterogeneous catalyst for the reaction between aryl cyanamides and sodium azide to synthesize the arylaminotetrazoles in good yields. This method has advantages of high yields, simple methodology, short reaction times an

Full text of DOI:10.1007/s12039-012-0348-8

c
J. Chem. Sci. Vol. 125, No. 1, January 2013, pp. 153–157. ꢀ Indian Academy of Sciences.
Nano indium oxide as a recyclable catalyst for the synthesis
of arylaminotetrazoles
SIAVASH BAHARI∗ and MEHDI AHMADI SABEGH
Department of Chemistry, Ahar Branch, Islamic Azad University, Ahar, 5451116714, Iran
e-mail: siavashbahari89@gmail.com; s-bahari@iau-ahar.ac.ir
MS received 18 February 2012; revised 17 May 2012; accepted 18 June 2012
Abstract. Nano indium oxide is an effective heterogeneous catalyst for the reaction between aryl cyanamides
and sodium azide to synthesize the arylaminotetrazoles in good yields. This method has advantages of high
yields, simple methodology, short reaction times and easy work-up. The catalyst can be recovered and reused
in good yields.
Keywords. Arylaminotetrazole; aryl cyanamides; nano indium oxide; reusable catalyst.
1. Introduction
such as natrolite zeolite (local zeolite)21 and ZnCl2.22
The development of a catalytic synthetic method for
tetrazoles still remains an active research area.
In recent years there has been a tremendous interest
in various chemical transformations performed under
the heterogeneous catalysis. Among heterogeneous cata-
lysts, metal nanoparticles have been used widely as
efficient catalysts in organic reactions due to their high
catalytic activity, ease of handling, reusability, and
benign character.23–28 Indium (III) compounds are mild
and water-tolerant Lewis acids and show high regio-,
stereo-, and chemoselectivity.29–33 However, until now
the use of nano In2O3 as a catalyst is limited in organic
synthesis.34
Despite the scarcity of tetrazoles in natural systems,
the chemistry of this heterocycle has gained increas-
ing attention since the early 1980s. Tetrazoles have a
wide range of applications as lipophilic spacers and
carboxylic acid surrogates in pharmaceuticals, as spe-
cial explosives and information recording systems in
materials, as ligands in coordination chemistry and as
precursors to a variety of nitrogen-containing com-
pounds.1–8
The conventional method of synthesizing tetrazoles
is by addition of azide ions to organic nitriles or
cyanamides.9–14 Earlier reported methods for the syn-
thesis of arylaminotetrazoles suffer from drawbacks
such as poor yield, long reaction times, harsh reac-
tion conditions; difficulty of obtaining and/or start-
ing materials preparation, tedious work-up, the use of
expensive and toxic metal reagents, and the in situ-
generated hydrazoic acid, which is highly toxic and
explosive.15–19 On the other hand, in most cases only the
1-aryl-5-amino-1H-tetrazoles were obtained.
Here, we describe an efficient method for the prepa-
ration of arylaminotetrazoles using nano In2O3 as a
heterogeneous catalyst (scheme 2).
2. Experimental
2.1 General
Nasrollahzadeh and co-workers have shown that
cyanamides may be converted to arylaminotetrazoles
using FeCl3–SiO2 as a heterogeneous catalyst which
often result in a mixture of isomers 5-arylamino-
1H-tetrazoles (isomer A) and 1-aryl-5-amino-1H-
tetrazoles (isomer B) (scheme 1).20
Several syntheses of arylaminotetrazoles have
been reported through the [2+3] cycloaddition of
cyanamides using NaN3 in the presence of catalysts
All reagents were purchased from Merck and Aldrich
chemical companies and used without further purifica-
1
tion. Products were characterized by FT-IR, H NMR
and 13C NMR, elemental analysis (CHN), and melt-
1
ing points. H NMR spectra were recorded on Bruker
Avance DRX 250, 300 and 500 MHz instruments.
NMR spectra were recorded in CDCl3, DMSO-d6 and
acetone-d6. Chemical shifts (δ) are reported in ppm
relative to tetramethylsilane (TMS) as internal stan-
dard. J values are given in Hz. 13C NMR spectra were
recorded at 125 and 75 MHz. FT-IR (KBr) spectra
∗For correspondence
153

154
Siavash Bahari and Mehdi Ahmadi Sabegh
Scheme 1. Synthesis of arylaminotetrazoles by the FeCl3–SiO2.
Scheme 2. Synthesis of arylaminotetrazoles by the nano In2O3.
were recorded on PerkinElmer 781 spectrophotometers. apparatus and are uncorrected. Thin-layer chromatog-
Melting points were obtained on a Reichert 7905 hot- raphy (TLC) was performed on silica gel polygram SIL
stage microscope or an Electrothermal IA9000 capillary G/UV 254 plates.
Table 1. Synthesis of arylaminotetrazoles (3) via secondary aryl cyanamides (1) catalysed by nano In2O3.
Entry
Ar
Product
3 (A or B)
Time (min)
Yielda%
m.p.(◦) [lit. mpref]
218–220 [218–22021]
272–274 [273–27421]
1
2
4-NO2-C6H4
2,5-(Cl)2-C6H3
3a (A)
110
81
3b (A)
110
80
3
4
3c (A)
100
60
82
86
214–215 [215–21721]
C6H5
2,6-(Me)2-C6H3
3d (B)
148–150 [147–14922b
]
H2N
N
N
N
N
5
6
4-Me-C6H4
2-Me-C6H4
3e (B)
3f (B)
60
60
80
84
177–178 [175.5–17716]
191–192 [191–19221]
199–201 [199–20121]
H3C
7
8
2,4-(Me)2-C6H3
1,4-C6H4
3g (B)
3h (B)
60
55
83
84
NH2
H2N
N
N
N
N
N
220–221 [220–22114c
]
N
N
N
aYield refers to pure isolated products

Nano indium oxide as a recyclable catalyst for the synthesis
155
2.2 General procedure for the synthesis
of arylaminotetrazoles
2H), 7.42 (t, J = 7.7 Hz, 1H); 13C NMR (125 MHz,
DMSO-d6): 16.8, 125.2, 128.3, 135.9, 136.0, 155.2;
Anal. Calcd for C9H11N5: C, 57.12; H, 5.86; N, 37.02.
Found: C, 57.19; H, 5.91; N, 37.09.
Nano In2O3 (0.1 g) was added to a mixture of
cyanamides (1a–h) (2 mmol), NaN3 (0.2 g, 3 mmol)
in distilled dimethylformamide (5 mL) and stirred at
120◦C for the appropriate time (table 1). After com-
pletion of the reaction (as monitored by TLC), the cat-
alyst was centrifuged, washed with ethyl acetate and
the centrifugate was treated with ethyl acetate (35 mL)
and 5 N HCl (20 mL). The resultant organic layer was
separated and the aqueous layer was again extracted
with ethyl acetate (20 mL). The combined organic lay-
ers were washed with water, concentrated, and washed
with ethanol to give different arylaminotetrazoles. The
physical data (mp, IR, NMR) of known compounds
were found to be identical to those reported in the
literature.21,22
5-Arylamino-1H-tetrazoles isomers (A) contain two
NH bonds (NH of the amine attached to the aryl
group (NHA) and NH of the tetrazole ring (NHT))
and 1-aryl-5-amino-1H-tetrazoles isomers (B) contain
a NH2 bond. The disappearance of one strong and
sharp absorption band (CN stretching band) and the
appearance of a NH stretching band in the IR spec-
tra provided clear evidence for the formation of aryl-
aminotetrazoles. 13C NMR spectra displayed signals at
δ = 154–157.5 ppm, indicative of C5 in the tetrazole
ring.21,22
3. Results and discussion
The cyanamides were prepared according to the lite-
rature.14b The general synthetic method is depicted in
scheme 1. Arylaminotetrazoles were obtained from the
reaction of cyanamides with sodium azide in the pre-
sence of nano In2O3 as an efficient heterogeneous cata-
lyst at 120◦ for the appropriate time in good yields
(table 1).
To show the advantages of nano In2O3, its reac-
tion was compared with FeCl3–SiO2, glacial HOAc,
ZnCl2 and Natrolite zeolite in the synthesis of 5-(2,5-
dichlorophenyl)amino-1H-tetrazole (3c). As shown in
table 2, nano In2O3 is an effective catalyst since the
products are regiospecific, whereas with FeCl3–SiO2
and glacial HOAc, a mixture of isomers will be pro-
22
duced. ZnCl2 is homogeneous which cannot be sepa-
rated from the reaction mixture, while nano In2O3 is
heterogeneous and can easily be recovered and reused.
Natrolite zeolite21 is a good catalyst, but there are dif-
ficulties in the preparation and availability of catalyst.
Not many organic solvents are suitable for the cycload-
dition reactions which usually need high temperatures
(sometimes as high as 130◦), and so DMF is a most
commonly used solvent for this purpose.2,20,21 The opti-
2.2a 1-(2,6-Dimethylphenyl)-5-amino-1H-tetrazole mum amount of nano In2O3 was found to be 0.1 g in
(3d): M.P. 148–150◦; FT-IR (KBr): 3441, 3383, the presence of cyanamide (2 mmol) and sodium azide
3351, 2952, 2921, 1697, 1651, 1604, 1583, 1558, (3 mmol) in DMF (6 mL). We have also examined a
1526, 1486, 1442, 1247, 1228, 1194, 1168, 1032, 987, variety of structurally divergent phenylcyanamide pos-
1
938, 780 cm−1; H-NMR (500 MHz, DMSO-d6, δ / sessing a wide range of functional groups to under-
ppm): 1.92 (6H, s), 6.67 (2H, s), 7.30 (d, J = 7.7 Hz, stand the scope and generality of nano In2O3-promoted
Table 2. Comparison of nano In2O3 activity with other reagents in the synthesis of arylaminotetrazoles.
Entry
Catalyst
Solvent
Time (min)
Yielda%
Product (A or B)
1
2
3
4
5
6
7
8
9
10
FeCl3-SiO2 (0.1 g)
Glacial HOAc (3 mL)
ZnCl2 (0.4 g)
Natrolite zeolite (0.1 g)
Natrolite zeolite (0.1 g)
Nano In2O3 (0.05 g)
Nano In2O3 (0.07 g)
Nano In2O3 (0.10 g)
Nano In2O3 (0.10 g)
Nano In2O3 (0.15 g)
DMFb
Glacial HOAcc
H2Oe
120
30 hd
15 h
9 h
76
72
84
49
81
69
73
80
80
81
A+B
A+B
A
A
A
A
A
A
A
H2Oe
DMFf
DMF
DMF
DMF
DMSO
DMF
95
120
120
120
120
120
A
aIsolated yield. bUnder thermal conditions at 110◦. cGlacial acetic acid as both solvent and proton source. dRoom temperature.
eUnder reflux conditions. fUnder thermal conditions at 110–115◦

156
Siavash Bahari and Mehdi Ahmadi Sabegh
cycloaddition reaction to form arylaminotetrazoles and
the results are summarized in table 1.
The products were completely regiospecific. This
observation is in contrast with those reports that the
other reagents will often produce a mixture of isomers
(scheme 3).
As shown in table 1, cyanamides having methyl as an
electron releasing group (entries 4–7) were completed
at 120◦ after 60 min, while the species bearing the
electron withdrawing groups NO2 or Cl (entries 1–2)
require higher reaction times.
Scheme 4. Synthesis of arylaminotetrazoles by the hydra-
zoic acid.
The influences of various substituents in different
ortho, meta or para positions on the type of products
were examined. Generally, when the substituent on the
aryl ring of 1 is electron-releasing, formation of 1-aryl-
5-amino-1H-tetrazoles (B) is favoured via the guani-
dine azide intermediate Bꢀ (table 1, entries 4, 5, 6 and
7), while with electron-withdrawing substituents the
product is shifted toward the formation of 5-arylamino-
1H-tetrazoles (A) via the guanidine azide intermedi-
ate Aꢀ (table 1, entries 1 and 2). In the earlier research
carried out, the nature of the substituent did not have
any effect.15–17,35–37 In the previously reported meth-
ods, substituents as different in their electrical effects
as the methyl group and the p-nitrophenyl group per-
mit the formation of the same type of compound (iso-
mer B).17 No clear explanation was given by the pre-
vious workers about the isolation or detection of other
isomers, although Stolle and Heintz reported the isola-
tion of 5-anilinotetrazole in low yield from the reaction
of phenylthiourea with lead oxide and sodium azide.38
In other words, in the synthesis of aminotetrazoles from
cyanamides, only the 1-aryl-5-amino-1H-tetrazole (B)
or a mixture of isomers (A + B) was obtained (scheme
4).13,20
HN3, FeCl3-SiO2 and glacial HOAc, 1-(4-nitrophenyl)-
5-amino-1H-tetrazole (isomer B) or a mixture of iso-
mers (A + B) was obtained.
The mechanism of the catalysis may originate from
the nitrile group coordinating with the surface of the
solid acid. The solid acid is supposed to activate the
nitriles and enhance their reactivity with sodium azide.
However, further experiments are necessary to gain a
clearer insight into these reactions.
The catalyst recycling is an important step as it
reduces the cost of the process. Nano In2O3 was recov-
ered quantitatively by simple centrifugation and reused
for three cycles with consistent activity. This reusabi-
lity demonstrates the high stability and turnover of nano
In2O3 under operating conditions.
4. Conclusion
We have developed a simple and efficient method for
the synthesis of arylaminotetrazoles by treatment of
cyanamides with sodium azide in the presence of nano
In2O3 as an effective heterogeneous catalyst. The sig-
nificant advantages of this methodology are high yields,
elimination of dangerous and harmful hydrazoic acid,
a simple work-up procedure, and easy preparation and
handling of the catalyst. The catalyst can be recovered
by filtration and reused.
Due to the presence of two CN groups, 1 h (table 1,
entry 8) interestingly afforded the double-addition
product.
4-Nitrophenylcyanamide interestingly gave 5-(4-
nitrophenyl)amino-1H-tetrazole (isomer A), while with
Acknowledgements
FeCl3-SiO2
A + B
We are thankful to the Islamic Azad University, Ahar
Branch for partial financial support to carry out this
research work.
DMF, 110 oC
Glacial HOAc
+
NaN3
A + B
A + B
Ar-NH-CN
rt
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Scheme 3. Synthesis of arylaminotetrazoles under differ-
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