A versatile and an efficient synthesis of 5-substituted-1H-tetrazoles

Article abstract of DOI:10.1007/s12039-011-0065-8

A simple, efficient and a versatile method for the synthesis of 5-substituted-1H-tetrazoles by a [3+2]-cycloaddition reaction of arylnitriles with sodium azide in DMF using ZrOCl₂.8 H₂O as catalyst has been developed. The reactions work well at 100°C and give the desired products in excellent yield. The examples studied include arylnitriles having electron donating as well as electron releasing groups on the arene nucleus. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0065-8

J. Chem. Sci., Vol. 123, No. 1, January 2011, pp. 75–79. * Indian Academy of Sciences.
A versatile and an efficient synthesis of 5-substituted-1H-tetrazoles
MADHUSUDANA REDDY MUTHUKUR BHOJE GOWD
and MOHAMED AFZAL PASHA*
Department of Studies in Chemistry, Central College Campus, Bangalore University,
Bangalore 560 001, India
e-mail: m_af_pasha@ymail.com
MS received 17 June 2010; revised 2 November 2010; accepted 4 November 2010
Abstract. A simple, efficient and a versatile method for the synthesis of 5-substituted-1H-tetrazoles by a
[
3+2]-cycloaddition reaction of arylnitriles with sodium azide in DMF using ZrOCl ·8 H O as catalyst has
2 2
been developed. The reactions work well at 100°C and give the desired products in excellent yield. The
examples studied include arylnitriles having electron donating as well as electron releasing groups on the
arene nucleus.
Keywords. Tetrazoles; ZrOCl ·8 H O; DMF; arylnitriles; sodium azide.
2
2
1
1b,c
1
. Introduction
tetrazoles.
Trimethylsilyl azide is also volatile and
11d
toxic reagent. More recently, CuO, triethylammo-
Tetrazoles are a class of heterocycles that have nium chloride in nitrobenzene, ZnCl and Tungsta-
received attention due to their wide range of applica- tes have been reported for the promotion of this
11e
2
11f
1
tions. In general, this nitrogen-rich ring system is used reaction.
in propellants, explosives, and in pharmaceuticals.
2
3
4
In order to overcome the limitations, syntheses
In addition, tetrazoles are important synthons in have been designed either to control the hydrazoic
5
12
synthetic organic chemistry, and also used as pre- acid formation or to use a large excess of azide ions
6
13
cursors of carbenes in flash vacuum pyrolysis. Various in the presence of metal catalysts or strong Lewis
tetrazole-based compounds have also shown good acids. Overall, these procedures are less desirable
coordination properties and are able to form stable due to the disadvantages of long reaction durations,
1
4
7
complexes with several metal ions. Furthermore, the low yield of products. The use of sodium azide as
tetrazole ring has strong electronwithdrawing property substrate in place of the hydrazoic acid or TMS-N3
and tetrazolyl halides have been successfully used in would be practically convenient. Zirconium com-
organic synthesis as derivatising agents for the chem- pounds on the other hand, are reported as excellent
8
15
ical modification of alcohols.
catalysts for various organic reactions. Among the
One of the well-known methods of synthesis of 5- various zirconium compounds, zirconyl chloride is
1
6
substituted-1H-tetrazoles is by a [3+2]-cycloaddition most effective, relatively non-toxic, inexpensive and
9
between hydrazoic acid and cyanides. While hydra- non-sensitive to air. A wide range of applications of
zoic acid is highly poisonous, explosive and low zirconyl chloride as a catalyst in organic synthesis are
1
7a
boiling liquid (~37ºC); trialkyltin azide (used in the reported. Some of them include oxidation,
acyla-
1
7b
17c–e
17f
synthesis of tetrazoles) is also volatile and toxic tion,
esterification,
nitration,
Michael addi-
1
0
17g
17h
17i
reagent, and is not readily available. Recently, tion, Mannich-type reactions, Biginelli reaction,
methods using trimethylsilyl azide (TMS-N ) are synthesis of 2-aliphatic aryloxazolines, synthesis of
reported by Yamamoto et al., for the synthesis of 5- benzimidazoles, synthesis of benzothiazoles, and
1
7j
3
1
7k
17l
11a
17m
substituted-tetrazoles;
and 2-allylated-5-substituted- synthesis of bis-oxazolines.
Recently, zirconyl
chloride has been proved to be highly effective
1
8a
catalyst for the synthesis of β-acetamido ketones,
1
8b
*
For correspondence
enaminones and enamino esters, α-aminophospho-
7
5

7
6
Madhusudana Reddy Muthukur Bhoje Gowd and Mohamed Afzal Pasha
1
8c
18d
nates,
1
homoallylic alcohols or amines
and catalyst was separated by filtration, washed with ethyl
acetate and the filtrate was taken into ethyl acetate
1
8e
,8-dioxo-octahydroxanthenes.
In continuation of our work on the synthesis of (30 mL) and 5N HCl (20 mL) was then added and
biologically important compounds using simple, effi- stirred vigorously. The organic layer was separated,
1
9
cient, non-toxic and readily available catalysts, we and the aqueous layer was washed with ethyl acetate
report herein the synthesis of 5-substituted-1H-tetra- (20 mL), and the combined extract was washed with
zoles by a [3+2]-cycloaddition reaction of arylnitriles water, dried over anhydrous Na SO and concentrated
2
4
with sodium azide in DMF using ZrOCl ·8 H O as a to get the crude crystalline 5-(4'-methoxyphenyl)-1H-
2
2
catalyst (scheme 1).
tetrazole. Column chromatography was performed
using silica gel (100–200 mesh) to afford pure product
as white solid (0·316 g, 90%), mp = 230–232°C. IR
2
. Experimental
−
1
(
KBr, ν cm ) 3200–3300 (br), 1298, 1184, 1035, 750;
1
2
.1 Materials
H NMR (400 MHz, DMSO-d ): δ 3·82 (3 H, s), 7·13
6
(
2 H, d, J = 9·0 Hz), 7·95 (2 H, d, J = 9·0 Hz); GC-
All solvents and reagents were commercial and used MS: m/z 175·1.
without further purification unless otherwise stated.
Nitrile (1h, table 1) was prepared from corresponding 3. Results and discussion
20
aldehyde as reported in the literature.
In search of an effective catalyst and to optimize the
experimental conditions, the reaction of 4-
methoxybenzonitrile and sodium azide was consid-
2
.2 Apparatus
Melting points were determined on a Raaga, Chennai, ered as the model reaction, and various zirconium
India melting point apparatus. Nuclear magnetic compounds were tested as catalysts. The best results
resonance spectra were obtained on a Bruker AMX were obtained by using 10 mol % of ZrOCl ·8H O
2
2
spectrophotometer in DMSO-d at 400 MHz instru- (table 2, entry e) in DMF as a solvent at 100°C after 6
6
ment. Chemical shifts are obtained in parts per million h to get the respective product in 90% yield. Under
(δ) and are measured using tetramethylsilane (TMS) as similar conditions, other zirconium compounds such
reference. GC-MS spectra were obtained on a Shi- as ZrO , ZrCl and ZrO(ClO ) ·6H O gave lower
2
4
4 2
2
madzu GC-MS QP 5050A (equipped with a 30 meter yields of tetrazole even after 10 h (table 2, entries a–
length and 0·32 mm of diameter BP-5 column with the c). Other metal catalysts such as CuCl , FeCl , NiCl
2
2
3
column temperature 80–15–250°C). IR spectra were or CoCl were also less effective in the promotion of
2
recorded on a Shimadzu FT-IR-8400s Spectropho- this reaction (table 2, entries f–i). The effect of
tometer using KBr pellets and are reported as wave solvent on the formation of tetrazoles was also
−
1
numbers (ν cm ).
studied. Use of other solvents (other than DMF) such
as DCM, MeCN and MeOH at reflux required longer
time (20h) to give the desired product in 30%, 61%
and 45% yield respectively. The necessity to use the
catalyst was realized by the observation that no
2
.3 General procedure for preparation
of 5-(4′-methoxyphenyl)tetrazole (2e)
ZrOCl ·8H O (10 mol%) is added to a mixture of 4- product was detected when the reaction was carried
2
2
methoxybenzonitrile (0·266 g, 2 mmol), sodium azide out in the absence of any catalyst either at room
0·195 g, 3 mmol) in DMF (5 mL) and stirred at 100°C temperature or at 100°C under neat conditions (table 2,
(
for 6 h. After completion of the reaction (TLC), the entry d).
N
HN
N
N
N
NaN / DMF
3
R
R
o
ZrOCl .8H O / 100 C
2
2
1
2
Scheme 1. Synthesis of 1H-tetrazoles from nitriles and catalytic ZrOCl ·8H O.
2
2

A versatile synthesis of 5-substituted-1H-tetrazoles
77
Table 1. Synthesis of tetrazoles from aromatic nitriles with sodium azide.
b
Entry
Nitrile(1)
Tetrazole(2)a
Time(h)
6
Yield(%)
N
HN
N
N
N
95
a
N
HN
N
N
N
6.5
93
90
88
90
88
b
c
d
e
f
H C
H C
3
3
N
N
HN
6
6
6
5
N
N
Cl
Cl
N
HN
N
N
N
HO
HO
N
HN
N
N
N
MeO
MeO
MeO
N
HN
N
N
N
MeO
N
HN
N
N
N
N
.
g
h
i
5 5
92
91
93
87
O N
O N
2
2
N
HN
N
N
O N
2
O N
2
5
5
9
NO2
NO2
N
N
HN
N
N
O
O
H
N
j
N
N
N
N
a
b
All reactions were performed using a nitrile (2 mmol), sodium azide (3 mmol) and ZrOCl ·8H O (10 mol%).
2
2
Isolated yield; and All the compounds are known and physical properties agree with literature values [refs. 9-11].

7
8
Madhusudana Reddy Muthukur Bhoje Gowd and Mohamed Afzal Pasha
Table 2. Effect of catalyst on the formation of 5-(4'-
methoxyphenyl)-1H-tetrazole.
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a
Entry Catalyst
Time(h)/Temp
°C)
Yield, 2e
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Cl, −OCH , −NO and −OH that do not interfere
3
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