Cross-linked poly (4-vinylpyridine) supported azide ion as a versatile and recyclable polymeric reagent for synthesis of 1-substituted-1H-1,2,3,4- tetrazoles

Article abstract of DOI:10.1007/s13738-013-0279-4

Cross-linked poly (4-vinylpyridine) supported azide ion, [P ₄-VP]N₃, is easily prepared and used as an efficient polymeric reagent for synthesis of 1-substituted-1H-1,2,3,4-tetrazoles via condensation reaction of azide ion, primary aromatic amines, and triethyl orthoformate in glacial acetic acid. After optimization of the reaction conditions, a wide variety of primary aromatic amines were also subjected to preparation of the corresponding 1-aryl-1 H-1,2,3,4- tetrazoles using [P ₄-VP]N₃ under heterogeneous conditions. In this method, the reaction times were very short and the isolated yields were excellent (90-98 %). 1-Aryl-1H-1,2,3,4- tetrazole products were characterized by Fourier transform infrared (FT-IR) and some of them were also characterized by proton nuclear magnetic resonance (¹H NMR) spectroscopy, and physical properties were compared with the literature values of known compounds. The spent polymeric reagent were regenerated quantitatively and reused for several cycles without significant loss of their activity.

Full text of DOI:10.1007/s13738-013-0279-4

J IRAN CHEM SOC
DOI 10.1007/s13738-013-0279-4
ORIGINAL PAPER
Cross-linked poly (4-vinylpyridine) supported azide ion
as a versatile and recyclable polymeric reagent for
synthesis of 1-substituted-1H-1,2,3,4-tetrazoles
Mohammad Ali Karimi Zarchi Fatemeh Nazem
•
Received: 26 January 2013 / Accepted: 22 May 2013
Ó Iranian Chemical Society 2013
Abstract Cross-linked poly (4-vinylpyridine) supported
azide ion, [P -VP]N , is easily prepared and used as an
in the production of large amounts of products. However,
recently the chemistry of functional polymers has received
great attention and has become a practical method for the
efficient preparation of novel chemical libraries [2–4].
Polymer-supported reagents particularly anion exchange
resins have been widely applied in organic synthesis
[2–16]. These polymeric reagents have been used in the
production of large number of products in single step
reactions. The advantages of this technique over conven-
tional classical methods are mild reaction conditions, safe
handling, rapid, and very simple work-up. On the other
hand, usually the spent polymeric reagents can be regen-
erated and reused for several times without significant loss
of their activity.
4
3
efficient polymeric reagent for synthesis of 1-substituted-
H-1,2,3,4-tetrazoles via condensation reaction of azide
1
ion, primary aromatic amines, and triethyl orthoformate in
glacial acetic acid. After optimization of the reaction
conditions, a wide variety of primary aromatic amines were
also subjected to preparation of the corresponding 1-aryl-1
H-1,2,3,4- tetrazoles using [P -VP]N under heterogeneous
4
3
conditions. In this method, the reaction times were very
short and the isolated yields were excellent (90–98 %).
1
-Aryl-1H-1,2,3,4- tetrazole products were characterized
by Fourier transform infrared (FT-IR) and some of them
were also characterized by proton nuclear magnetic reso-
1
nance ( H NMR) spectroscopy, and physical properties
In recent years, the number of publications and patents
describing the synthesis and investigations of the structural
and physicochemical properties of tetrazoles has grown
intensely. This is due to the wide range of practical
applications of these compounds. For example, 1-substi-
tuted tetrazoles have been used in different application in
many important field such as medicinal chemistry [17],
coordination chemistry [18, 19], color photography cou-
plers [20], agriculture [21], and high energy density
materials with high nitrogen contents [22, 23].
were compared with the literature values of known com-
pounds. The spent polymeric reagent were regenerated
quantitatively and reused for several cycles without sig-
nificant loss of their activity.
Keywords 1-Substituted-1H-1,2,3,4-tetrazoles Á
Polymer-supported azide ion Á Aromatic amine Á
Triethyl orthoformate
In general, the most direct and versatile method of the
synthesis of tetrazoles is the cycloaddition between nitriles,
cyanates and cyanamides, and azides [24–29].
Introduction
The problems associated with classical multi-step synthesis
in solution may overcome by a modified technique that was
introduced by Merrifield [1]. This technique has been used
1-Substituted tetrazoles are generally synthesized by the
reaction of isocyanides with large excess amounts of dan-
gerous and harmful hydrazoic acid [30, 31] or trimethyl-
silyl azide [32].
Other methods of a tetrazole ring synthesis include
addition of primary amines or their salts to sodium azide
and orthocarboxylic acid ester in acetic acid or trifluoro-
acetic acid [33, 34]. Recently, 1-substituted tetrazoles were
M. A. Karimi Zarchi (&) Á F. Nazem
Department of Chemistry, College of Science,
Yazd University, P. O. Box 89195-74, Yazd, Iran
e-mail: makarimi@yazd.ac.ir
123

J IRAN CHEM SOC
prepared in ionic liquids [35, 36]. Habibi et al. [37] have
reported silica sulfuric acid as an efficient heterogeneous
catalyst for the solvent-free synthesis of 1-substituted 1H-
data with pure compounds. All yields refer to the isolated
products. FT-IR and NMR spectra were run on a Bruker
Equinox (model 55) and Bruker AC 500, respectively,
1
1
,2,3,4-tetrazoles. Habibi et al. [38] have also reported the
Aveance DPX spectrophotometer at 500 MHz for H-NMR
synthesis of 1-substituted 1H-1,2,3,4-tetrazoles in the
in CDCl , and DMSO solution (using tetramethylsilane as
3
presence of Natrolite zeolite. Su et al. [39] have reported
internal reference).
1
-substituted 1H-1,2,3,4-tetrazoles using Yb (OTf).
All of these known methods suffered from some limi-
Preparation of [P -VP]N
4
3
tation such as low yields; tedious work-up procedures; the
use of expensive and toxic metal catalysts; the use of high
boiling point solvent such as dimethyl formamide (DMF);
and complex isolation and recovery procedures. Therefore,
it is desirable to develop a convenient method for the
synthesis of 1-substituted 1H-1,2,3,4-tetrazoles.
Poly (4-vinylpyridine) cross-linked with 2 % DVB (white
powder, 100–200 mesh) (1.0 g) was added to a solution of
methyl iodide (20 mmol, 3.24 g) in acetonitrile (10 mL), and
the mixture was stirred slowly for 24 h at room temperature.
The yellow quaternized polymer, [P -VP]I, was filtered and
4
Although there are numerous applications of polymeric
reagents in literature, there are only a few reports in the
literature based on polymer-supported azide ion and there
is only one report on the synthesis of 5-substituted 1-H-
tetrazoles based on polymer-supported azide ion [29].
Hassner et al. [40] have reported the use of the polymeric
quaternary ammonium azide for synthesis of alkyl azides
from alkyl halides or esters. Previously, we have reported
the synthesis and application of cross-linked poly (4-
vinylpyridine) supported azide ion, [P -VP]N , for syn-
washed with acetone (3 9 5 mL). It was then dried under
vacuum in the presence of P O at 40 °C overnight.
2
5
The obtained [P -VP]I was added to 40 mL of a
-
4
1
3 mol L
aqueous solution of sodium azide and was
stirred slowly for 24 h. The prepared resin, [P -VP]N , was
4
3
filtered off and was washed with distilled water. It was then
washed with diethyl ether (5 mL) and dried under vacuum
in the presence of P O at 40 °C overnight. The capacity of
2
5
the polymer was determined by potentiometric titration of
-
1
the filtrates with a 0.1 mol L aqueous solution of silver
nitrate, and it was found to be 3.4 mmol per gram of the
polymer.
4
3
thesis of alkyl azides from alkyl halides [41]. Recently, we
also used this polymeric reagent for synthesis of 5-substi-
tuted 1-H-tetrazoles [40], diazotization–azidation of pri-
mary aromatic amines [42, 43], and synthesis of acyl azides
from acyl halides [44].
General procedure for synthesis of 1-substituted
1-H-1,2,3,4-tetrazoles
In continuation of our studies on the development of
application of cross-linked poly (4-vinylpyridine) sup-
ported azide ion, [P -VP]N , in organic synthesis [29, 41–
A suspension of a primary aromatic amine (1 mmol), tri-
ethyl orthoformate (2.5 mmol), and [P -VP]N (2.5 mmol)
4
3
4
3
4
4], herein, we wish to report an efficient and easy method
for preparation of 1-substituted 1-H tetrazoles using
P -VP]N /ArNH /CH(OEt) /AcOH at 100 °C.
in glacial acetic acid (5 mL) was stirred for appropriate
time as indicated in Table 2 (shown later) at 100 °C. The
progress of reaction was monitored by TLC (n-hexane/
ethyl acetate: 9/1). After completion of the reaction, etha-
nol (8 mL) was added to the reaction mixture and heated at
70 °C for 5 min. The reaction mixture was filtered off and
was washed with hot ethanol. Then, the solution was
[
4
3
2
3
Experimental
-
1
Materials
cooled to room temperature and 4 mL of 4 mol L
aqueous solution of HCl was added. The precipitated
product was filtered, washed with water, and dried to
obtain the pure product. When further purification was
needed, column chromatography on silica gel (eluent: n-
hexane/ethyl acetate: 9/1) was applied and highly pure
product was obtained.
Chemicals were either prepared in our laboratory or were
purchased from Fluka (Buchs, Switzerland), Aldrich
(
Milwaukee, WI, USA), and Merck chemical companies.
Poly (4-vinylpyridine) cross-linked with 2 % divinyl ben-
zene (DVB), [P -VP] 2 % DVB, was purchased from Fluka
4
company (Buchs, Switzerland) and [P -VP]N , was pre-
3
4
pared according to our reported procedure [29].
Preparation of 1-(4-chlorophenyl)-1H-1,2,3,4-tetrazole:
a typical procedure
The reactions were monitored by thin layer chroma-
tography (TLC) using silica gel Poly Gram SIL G/UV 254
plates. All products were characterized by comparison of
their Fourier transform infrared (FT-IR), proton nuclear
A suspension of 4-chloroaniline (1 mmol), triethyl ortho-
formate (2.5 mmol), and [P -VP]N (2.5 mmol) in glacial
4
3
1
magnetic resonance ( H-NMR) spectra, TLC, and physical
acetic acid (5 mL) was stirred for 10 min at 100 °C (The
1
23

J IRAN CHEM SOC
progress of reaction was monitored by TLC; n-hexane/
ethyl acetate: 9/1). After completion of the reaction, etha-
nol (8 mL) was added to the reaction mixture and heated at
2,211, 1,500, 1,461, 1,385, 1,205, 1,174, 1,085, 1,040, 995,
822.
7
0 °C for 5 min. The reaction mixture was filtered off and
was washed with hot ethanol. Then, the solution was
1-(4-Methylphenyl)-1H-1,2,3,4-tetrazole
-
1
1
cooled to room temperature and 4 mL of 4 mol L
White solid; mp: 93–94 °C; H NMR (500 MHz, CDCl ,
3
aqueous solution of HCl was added. The precipitated
product was filtered, washed with water, and dried to
obtain the pure product.
298 K): d (ppm) = 3.02 (s, 3H), 7.40 (d, J = 8.4 Hz, 2H),
7.62 (d, J = 8.4 Hz, 2H), 9.02 (s, 1H); FT-IR: m
(cm ) = 3,105, 2,211, 1,500, 1,461, 1,385, 1,205, 1,174,
max
-
1
1
Yield: 178 mg (98 %), white solid; mp: 160–162 °C; H
1,085, 1,040, 995, 822.
NMR (500 MHz, CDCl , 298 K): d (ppm) = 7.62 (2H, d,
3
J = 8.7 Hz), 7.73 (d, J = 8.7 Hz, 2H), 9.2 (s, 1H); FT-IR:
-
1-(4-Methoxyphenyl)-1H-1,2,3,4-tetrazole
1
mmax (cm ) = 3,105, 2,211, 1,500, 1,461, 1,385, 1,205,
1
1
,174, 1,085, 1,040, 995, 822.
White solid; mp: 117–118 °C; H NMR (500 MHz, CDCl ,
3
298 K): d (ppm) = 3.82 (s, 3H), 7.00 (d, J = 8.9 Hz, 2H), 7.58
-1
1
-Phenyl-1H-1,2,3,4-tetrazole
(d, J = 8.9 Hz, 2H), 9.04 (s, 1H); FT-IR: mmax (cm ) = 3,105,
,211, 1,500, 1,461, 1,385, 1,205, 1,174, 1,085, 1,040, 995, 822.
2
1
Yield: 131 mg (98 %), white solid; mp: 63–65 °C;
H
NMR (500 MHz, CDCl , 298 K): d (ppm) = 7.32 (t,
1-(4-Acetylphenyl)-1H-1,2,3,4-tetrazole
3
J = 7.4 Hz, 1H), 7.63 (t, J = 7.6 Hz, 2H), 7.76 (d,
-
1
1
J = 7.8, 2H), 9.07 (s, 1H); FT-IR: mmax (cm ) = 3,105,
White solid; mp: 174–175 °C; H NMR (500 MHz, CDCl ,
3
2
,211, 1,500, 1,461, 1,385, 1,205, 1,174, 1,085, 1,040, 995,
298 K): d (ppm) = 2.61 (s, 3H), 7.89 (d, J = 8.9 Hz, 2H),
8
22.
8.12 (d, J = 8.9 Hz, 2H), 9.37 (s, 1H); FT-IR: m
(
max
-
cm ) = 3,105, 2,211, 1,500, 1,461, 1,385, 1,205, 1,174,
1
1
-(4-Bromophenyl)-1H-1,2,3,4-tetrazole
1,085, 1,040, 995, 822.
1
Yield: 143 mg (98 %) white solid; mp: 180–181 °C; H
1-(4-Nitrophenyl)-1H-1,2,3,4-tetrazole
NMR (500 MHz, CDCl , 298 K): d (ppm) = 7.64 (d,
3
1
J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 9.23 (s, 1H);
1
Yellow solid; mp: 191–193 °C; H NMR (500 MHz, CDCl ,
3
-
FT-IR: mmax (cm ) = 3,125, 1,493, 1,383, 1,270, 1,210,
298 K): d (ppm) = 8.06 (d, J = 8.9 Hz, 2H), 8.38 (d,
J = 8.9 Hz, 2H), 9.64 (s, 1H); FT-IR: mmax (cm ) = 3,105,
,211, 1,500, 1,461, 1,385, 1,205, 1,174, 1,085, 1,040, 995, 822.
-1
1
,194, 1,178, 992, 815.
2
1
-(4-Iodophenyl)-1H-1,2,3,4-tetrazole
1
-(3-Nitrophenyl)-1H-1,2,3,4-tetrazole
1
White solid; mp: 196–197 °C; H NMR (500 MHz, CDCl ,
3
1
2
98 K): d (ppm) = 7.52 (d, J = 6.9 Hz, 2H), 7.98 (d,
J = 6.9 Hz, 2H), 9.03 (s, 1H); FT-IR: mmax (cm ) = 3,105,
,211, 1,500, 1,461, 1,385, 1,205, 1,174, 1,085, 1,040, 995, 822.
White solid; mp: 108–110 °C; H NMR (500 MHz, CDCl ,
298 K): d (ppm) = 7.78 (t, J = 8.2 Hz, 1H), 8.21 (d,
3
-1
2
Table 1 Optimization of the reaction conditions for synthesis of
1-(4-chlorophenyl)-1H-1,2,3,4-tetrazole (1 mmol) using [P -VP]N /
1
-(4-Hydroxy phenyl)-1H-1,2,3,4-tetrazole
4
3
3
CH(OEt) /AcOH
1
White solid; mp: 210–211 °C; H NMR (500 MHz,
Entry [P
VP]N
mmol)
4
-
CH(OEt)
(mmol)
3
Reaction
Reaction
Isolated
DMSO-d , 298 K): d (ppm) = 6.98 (d, J = 8.9 Hz, 2H),
3
time (min) temp. (°C) yield (%)
6
(
7
.68 (d, J = 8.9 Hz, 2H), 9.91 (s, 1H), 10.11 (s, 1H); FT-
1
-
IR: mmax (cm ) = 3,105, 2,211, 1,500, 1,461, 1,385,
1
2
3
4
5
6
7
8
3.4
2.5
2
3
10
10
30
60
10
60
60
60
100
100
100
100
100
r.t
98
98
98
51
98
0
1
,205, 1,174, 1,085, 1,040, 995, 822.
3
3
1
-(4-Ethylphenyl)-1H-1,2,3,4-tetrazole
2.5
2.5
2.5
2.5
2.5
2
2.5
2.5
2.5
2.5
1
White solid; mp: 77–78 °C; H NMR (500 MHz, CDCl ,
3
2
98 K): d (ppm) = 1.33 (t, J = 7.6 Hz, 3H), 2.79 (q,
J = 7.6 Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 7.65 (d,
65
50
78
75
-1
J = 8.2 Hz, 2H), 9.00 (s, 1H); FT-IR: mmax (cm ) = 3,105,
123

J IRAN CHEM SOC
Table 2 Synthesis of 1-Aryl 1 H-1,2,3,4-tetrazoles using ArNH
2 4 3
/[P -VP] N /CH(OEt)
3
in glacial acetic acid at 100 °C
a
Entry
1
Substrate (ArNH
2
)
Product
Time (min)
25
Yield (%)
m.p. (°C)
Ref.
C
6 5
H NH
2
90
63–65
35, 36, 37, 39, 45
b
2
4-ClC
6
H
4
NH
NH
2
2
10
10
98
98
160–162
160–162
35, 36, 37, 39, 45
35, 36, 37, 39, 45
N
N
Cl
N
N
4
-ClC
H
6 4
N
N
Cl
N
N
b
3
4-ClC
4-ClC
6
H
4
NH
NH
2
2
10
10
95
92
160–162
160–162
35, 36, 37, 39, 45
35, 36, 37, 39, 45
N
b
4
Cl
N
N
N
N
b
5
H
6 4
N
Cl
N
N
b
6
4-ClC
6
H
4
NH
2
10
15
15
5
92
98
97
96
160–162
180–181
196–197
210–211
35, 36, 7, 39, 45
N
N
Cl
Br
I
N
N
N
N
7
8
9
4-BrC
6
H
4
NH
2
37
N
N
4-IC
6
H
4
NH
2
–
–
N
N
N
N
4-OHC
6 4 2
H NH
N
N
HO
N
N
1
0
4-EtC
6
H
4
NH
2
25
95
77–78
–
N
Et
N
N
N
N
1
1
1
1
1
2
3
4
4-MeC
6
H
4
NH
2
20
15
10
10
95
98
97
98
93–94
35, 36, 37, 39, 45
N
Me
N
N
4-OMeC
6
H
4
NH
2
117–118
174–175
191–193
35, 36
36
N
MeO
MeOC
N
N
N
6 4 2
4-MeCOC H NH
N
N
N
N
4-NO
3-NO
2
C
6
H
4
NH
2
2
37
N
N
O
2
N
N
N
1
5
2
C
6
H
4
NH
O
2
N
15
95
108–110
45
N
N
N
N
1
23

J IRAN CHEM SOC
Table 2 continued
a
Entry
Substrate (ArNH
2
)
Product
Time (min)
10
Yield (%)
98
m.p. (°C)
Ref.
–
1
6
7
4-CO
2-CO
2
HC
HC
6
H
4
NH
2
196–197
N
N
HO
2
C
N
N
1
2
H
6 4
NH
2
CO
2
H
15
92
194–195
–
N
N
N
N
a
Isolated yields based on amines
b
4 3
The entries 3-6 refer to the use of the [P -VP]N that is recycled first, second, third, and fourth time, respectively, under identical conditions
J = 8.1 Hz, 1H), 8.30 (d, J = 8.1, 1H), 8.72 (s, 1H), 9.67
-
procedure for synthesis of 1-substituted 1-H tetrazoles
1
(
s, 1H); FT-IR: mmax (cm ) = 3,105, 2,211, 1,500, 1,461,
using [P -VP]N /ArNH /CH(OEt) in glacial acetic acid. It
4
3
2
3
1
,385, 1,205, 1,174, 1,085, 1,040, 995, 822.
is important to note that this polymeric reagent is stable
and can be stored for long time (months), without losing its
activity and can be readily used in condensation reaction
with primary aromatic amines and triethyl orthoformate in
glacial acetic acid for synthesis of different 1-substituted
1-H tetrazoles. We disclose a less hazardous and practical
synthesis of 1-aryl 1-H tetrazoles from their corresponding
aryl amines using a stable and nonexplosive polymeric
reagent, [P -VP]N . A good range of available primary
4
-(1H-1,2,3,4-Tetrazol-1-yl)benzoic acid
1
White solid; mp: 196–197 °C; H NMR (500 MHz,
DMSO-d , 298 K): d (ppm) = 8.08 (d, J = 8.6 Hz, 2H),
6
8
.19 (d, J = 8.6 Hz, 2H), 10.21 (s, 1H), 13.34 (s, 1H); FT-
-
1
IR: mmax (cm ) = 3,105, 2,211, 1,500, 1,461, 1,385,
1
,205, 1,174, 1,085, 1,040, 995, 822.
4
3
aromatic amines were also subjected to synthesis of 1-aryl
1-H tetrazoles under heterogeneous conditions (Scheme 1).
To increase the yield of tetrazole compounds, optimi-
zation of the reaction conditions was accomplished.
4-Chloroaniline (1 mmol) was chosen as a model substrate
and was treated with different molar ratio of [P -VP]N /
2
-(1H-1,2,3,4-Tetrazol-1-yl)benzoic acid
1
White solid; mp: 194–195 °C; H NMR (500 MHz,
DMSO-d , 298 K): d (ppm) = 7.72 (d, J = 7.8 Hz, 1H),
6
7
.79 (t, J = 7.6 Hz, 1H), 7.86 (t, J = 7.4, 1H), 8.10 (d,
4
3
J = 7.8, 1H), 9.83 (s, 1H), 13.69 (s, 1H); FT-IR: m
CH(OEt) , and the results are given in Table 1. It was
3
max
-
1
(
cm ) = 3,105, 2211, 1,500, 1,461, 1,385, 1,205, 1,174,
,085, 1,040, 995, 822.
observed that the 2.5/2.5 molar ratio of [P -VP]N /
4
3
1
CH(OEt) at 100 °C were the best conditions to achieve the
3
highest yield of the product. With increasing the temper-
Regeneration of [P4-VP]N3
ature and also with increasing the amounts of [P -VP]N
4
3
and CH(OEt) result in bouts of higher yields and lower
3
The spent cream-colored polymer (1 g) was added to a 40 mL
reaction times (Table 1).
-1
of a 3 mol L aqueous solution of sodium azide and was
stirred slowly for 24 h. The mixture was filtered and washed
with distilled water (3 9 8 mL) and dried under vacuum in
the presence of P O at 40 °C overnight. The capacity of the
regenerated polymer was determined, and it was found that it
had the same capacity as the original form (3.4 mmol of azide
ion per gram of polymer). The regenerated polymer was
reused several times, without losing its activity and the results
are given in Table 2, entries 3–6 (shown later).
We then applied these conditions for synthesis of various
1-aryl- 1-H tetrazoles and the results are given in Table 2.
Various aromatic amines, with electron withdrawing groups as
well as electron donating groups, were transformed into 1-aryl-
1 H tetrazoles in high to excellent yields (90–98 %, Table 2).
It was observed that under similar conditions, a wide
range of anilines containing electron withdrawing groups
as well as electron donating groups such as Cl, Br, I, OH,
CH CO, CO H OMe, Et, Me, and NO easily underwent
2
5
3
2
2
condensation with triethyl orthoformate and azide ion
Results and discussion
[
P4-VP]N3
N
N
Ar-NH2
+ CH(OEt)3
Ar
N
Cross-linked poly (4-vinylpyridine) supported azide ion,
CH CO H, 100 °C
3
2
N
[
P -VP]N , was easily prepared according to our previ-
4 3
ously reported procedure [29] and used as an efficient
Scheme 1 Preparation of 1-substituted 1 H-1,2,3,4-tetrazoles
123

J IRAN CHEM SOC
Table 3 Comparison of different methods for synthesis of 1-substituted-1H-1,2,3,4-tetrazoles
Entry
Reagents and reaction conditions
Time
Isolated yield (%)
Ref. (%)
1
2
3
4
5
6
7
RNH
RNH
RNH
RNH
RNH
RNH
RNH
2
2
2
2
2
2
2
/[P
4
-VP]N
3
/CH(OEt)
3
, AcOH, 100 °C
10–25 min
1–1.5 h
15–35 min
2.5–8 h
4 h
90–98
85–91
85–91
88–96
80–94
71–91
70–90
a
/NaN
/NaN
/NaN
/NaN
/NaN
/NaN
3
/CH(OEt)
3
/CH(OEt)
3
/CH(OEt)
3
/CH(OEt)
3
/CH(OEt)
3
3
3
3
3
3
, IL/DMSO, 30 °C
, [Hbim]BF
35
36
37
38
39
45
b
4
, 100 °C
, SSA, 120 °C, solvent-free
,Natrolite zeolite, 120 °C
, Yb(OTf)
3
, 100 °C
6–9 h
/CH(OMe)
3
, In(OTf)
3
1.5–3.5 h
IL/DMSO ionic liquids/dimethyl sulfoxide, SSA silica sulfuric acid
a
Present method (Table 2)
b
[
4
Hbim]BF : 1-n-butylimidazolium tetrafluoroborate
Scheme 2 Preparation stages
of [P -VP]N and the plausible
reaction pathway of tetrazole
synthesis and regeneration of
the polymeric reagent
1
) [P -VP] 2% DVB + CH -I
[P
NaI (aq) + [P -VP]N
4 3
4
-VP]I
4
3
4
3
2) [P -VP]I + NaN (aq)
4
3
N
[
P -VP]N , AcOH, 100 °C
4
3
+
[P -VP]CO CH
3
) ArNH + CH(OEt)3
Ar
N
N
4
2
3
2
-3 EtOH
N
Regeneration
) [P -VP]CO CH + NaN (aq)
[P -VP]N3 + NaCO CH (aq)
4 2 3 3
4
4
2
3
....
)
....
(
2
[
P -VP] 2% DVB: Poly (4-vinylpyridine) cross-linked with 2% divinylbenzene ,
4
.
...
(
)
)
....
(
9
8
2
N
Fig. 1 The FT-IR of 1-(4-
chlorophenyl)-1H-1,2,3,4-
tetrazole
(
supported on polymer) to give 1-substituted-1H-1,2,3,4-
work-up by a simple filtration. The reactions can be driven
to completion using excess amounts of reagent without the
fear of separation of the excess of reagent from the prod-
ucts. On the other hand, one of the most disadvantages of
the polymeric reagents is their expensive, but in this case,
appropriate chemistry is available (Scheme 2, step 4) and
tetrazoles in very short reaction times (10–25 min) with
excellent isolated yields (90–98 %, Table 2).
This polymeric reagent is used in single step reaction; its
main advantage over non-polymeric reagents is its insolu-
bility in the reaction medium and consequently, its easier
1
23

J IRAN CHEM SOC
1
Fig. 2 The H NMR of 1-(4-
chlorophenyl)-1H-1,2,3,4-
tetrazole
1
Fig. 3 The expanded H NMR
of 1-(4-chlorophenyl)-1H-
,2,3,4-tetrazole
1
the spent polymeric reagents can in principle be recycled
many times (Table 2, entries 3–6). In Scheme 2, prepara-
tion stages of [P -VP]N , the plausible reaction pathway of
as 2-methoxyethanol, DMF, or methanol and very harsh
reaction conditions such as refluxing for 6–24 h followed
by very tedious work-up procedures involving distillation
of high boiling solvents under reduced pressure. Compared
to the reported methods, our method is convenient, fast,
safe, and easy to work-up. In Table 3, the present method is
compared with other reported methods [35–39]. As Table 3
reveals in this procedure, the reaction times are shorter than
previously reported methods and the isolated yields are
higher. This can probably be attributed to the local con-
centration of azide ion species inside the pores.
4
3
tetrazole synthesis, and regeneration of the polymeric
reagent are shown.
We have also successfully applied this new method on a
rather large scale. For example, up to 15 mmol of 4-chloro-
aniline (Table 2, Entry 2) could be converted into 1-(4-chlo-
rophenyl)- 1H- 1,2,3,4-tetrazole without any loss of efficiency.
The methods reported so far for the synthesis of
1
-substituted tetrazoles required highly polar solvents such
123

J IRAN CHEM SOC
1
-Substituted 1H-tetrazole products were characterized
and the pyridine, rings of the polymer chains were quat-
-1
ernized; this peaks were shifted to 1,634 and 1,460 cm
1
by FT-IR and H-NMR spectroscopy, and physical prop-
erties were compared with the literature values. For
1
example, the FT-IR and H NMR spectra of 1-(4-chloro-
(b). Also when [P -VP]I was converted to [P -VP]N by an
4
4
3
ion exchange reaction with NaN (aq.), these peaks were
3
-
also shifted to 1,638 and 1,463 cm and the appearance of
1
phenyl)-1H-1,2,3,4-tetrazole are shown in Figs. 1, 2, and 3,
respectively. On the other hand, in Fig. 4, the FT-IR
spectra of [P -VP] 2 % DVB, [P -VP]I, [P -VP]N and
-
1
-1
a new peak at 2,005 cm indicates that the N3 ion was
supported on the polymer. This interaction increases the
stiffness of the associated ring and consequently, more
energy is required to deform the aromatic cycle, reflected
in a higher wave number value. Figure 4 reveals that the
FT-IR spectra of [P -VP]N (c) and regenerated polymer
4
4
4
3
regenerated polymer were compared (a, b, c, and d,
respectively). The pyridine pendent groups of the polymer
chain of [P -VP] 2 % DVB exhibit strong C=C stretching
4
-
1
-1
at 1,554 cm
and C=N stretching at 1,414 cm
(a).
4
3
When [P -VP] 2 % DVB was treated with methyl iodide
4
(d) are similar.
Fig. 4 The FT-IR spectra of
[
4
P -VP] 2 % DVB (a), [P
4
-VP]I
(
regenerated polymer (d)
b), [P -VP]N (c), and
4
3
1
23

J IRAN CHEM SOC
The advantages of this method over conventional clas-
sical methods are separation of the supports from the
reaction mixture by simple filtration, low reaction time, and
excess of a polymeric reagent can be readily used without
incurring complication in work-up. In addition, there is
current research and general interest in heterogeneous
systems because these systems have importance in industry
and in developing technologies [46].
13. M.A. Karimi Zarchi, N. Ebrahimi, J. Appl. Polym. Sci. 124, 2807
2012)
(
1
1
4. M.A. Karimi Zarchi, N. Ebrahimi, Iran. Polym. J. 21, 591 (2012)
5. M.A. Karimi Zarchi, N. Ebrahimi, J. Appl. Polym. Sci. 125, 2163
(2012)
16. M.A. Karimi Zarchi, N. Ebrahimi, Phosphorous Sulfur 187, 1226
2012)
(
7. L. Myznikov, A. Hrabalek, G. Koldobskii, Chem. Heterocycl
Com. 43, 1 (2007)
1
18. E.A. Popova, R.E. Trifonov, V.A. Ostrovskii, Arkivoc 1, 45
2012)
9. H. Zhao, Z.R. Qu, H.Y. Ye, R.G. Xiong, Chem. Soc. Rev. 37, 84
2008)
0. O.E. Alawode, C. Robinson, S. Rayat, J. Org. Chem. 76, 216
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(
1
2
(
Conclusions
(
In conclusion, we have developed a mild, convenient, and
efficient method for the synthesis of 1-aryl-1H-1,2,3,4-
tetrazoles via condensation reaction of azide ion, primary
aromatic amines, and triethyl orthoformate in glacial acetic
acid under heterogeneous conditions in excellent yields.
The present method has the advantages of operational
simplicity, mild reaction conditions, ready availability, fast
reaction rates, and simple reaction work-up. The spent
polymeric reagents can be recovered by simple filtration
and after regeneration with sodium azide, reused several
times without significant loss of their activity. The product
can also be obtained by simple filtration and evaporation of
the solvent.
21. R.J. Nachman, G.M. Coast, K. Kaczmarek, H.J. Williams, J.
Zabrocki, Biopolymers 75, 412 (2004)
2
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7
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9
(
(
(
1
1
1
(
(
(
123