Nanocrystalline ZnO as an efficient heterogeneous catalyst for the synthesis of 5-substituted 1H-tetrazoles

Article abstract of DOI:10.1002/adsc.200505011

Nanocrystalline ZnO is an effective heterogeneous catalyst for the [2 + 3]-cycloaddition of sodium azide with nitriles to afford 5-substituted 1H-tetrazoles in good yields.

Full text of DOI:10.1002/adsc.200505011

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Nanocrystalline ZnO as an Efficient Heterogeneous Catalyst for
the Synthesis of 5-Substituted 1H-Tetrazoles
M. Lakshmi Kantam,* K. B. Shiva Kumar, Ch. Sridhar
Inorganic Chemistry Division, Indian Institute of Chemical Technology, Hyderabad – 500007, India
Fax: (þ91)-40-27160921; e-mail: mlakshmi@iict.res.in
Received: January 11, 2005; Accepted: April 11, 2005
Abstract: Nanocrystalline ZnO is an effective heter-
ogeneous catalyst for the [2þ3]-cycloaddition of so-
dium azide with nitriles to afford 5-substituted 1H-
tetrazoles in good yields.
Scheme 1. Nano ZnO-catalyzed synthesis of 5-substituted
1
H-tetrazoles.
Keywords: [2þ3]-cycloaddition; heterogeneous cata-
lyst; nano ZnO; 5-substituted 1H-tetrazoles
Herein, we report the synthesis of 5-substituted 1H-
tetrazoles from a wide variety of organic nitriles with so-
dium azide using nano ZnO catalyst (Scheme 1).
In an effort to develop a better catalytic system, vari-
Tetrazoles have a wide range of applications in pharma- ous reaction parameters were studied for the prepara-
ceuticals as lipophilic spacers and carboxylic acid surro- tion of 5-phenyltetrazole by the reaction of benzonitrile
gates, in materials as specialty explosives and informa- with sodium azide and the results are summarized in Ta-
tion recording systems, in coordination chemistry as li- ble 1. The solvent has a pronounced effect in these reac-
gands and also as precursors to a variety of nitrogen-con-
[
1]
taining heterocycles. Generally, 5-substituted 1H-tet-
razoles are prepared by the addition of azides to
[2]
nitriles. The earlier reported methods suffer from Table 1. Screening of reaction parameters for the formation
[a]
some disadvantages like use of strong Lewis acids, ex- 5-phenyltetrazole.
pensive and toxic metals and the in situ generated hydra-
zoic acid is highly toxic and explosive. Later, Sharpless
and co-workers reported an innovative and safe proce-
dure for the synthesis of tetrazoles by the addition of so-
dium azide to nitriles using stoichiometric amounts of
[
3]
Zn(II) salts in water. Very recently, Pizzo and co-work-
ers efficiently synthesized tetrazoles by the addition of
TMSN to organic nitriles using 10 mol % TBAFas cat-
3
[4]
alyst.
In recent years, there has been increasing emphasis on
the use and design of environmentally friendly solid cat-
alysts to reduce the amount of toxic waste. Nanocrystal-
[5]
line metal oxides have been efficiently used as absorb-
ents for gases and destruction of hazardous chemicals
and as catalysts for organic transformations such as ep-
[6]
[7]
oxidation, benzylation, etc. These high reactivities
are due to high surface areas combined with unusually
reactive morphologies.
ZnO is an important semiconductor material and has
been used widely in pigments, cosmetics, chemical sen-
[
a]
Reaction
conditions:
nitrile
(2.5 mmol),
NaN3
[
8]
(2.75 mmol), nano ZnO (0.1 g), DMF (5 mL), reaction
time (14 h), 120–1308C.
Yield of isolated products.
Yield after third cycle.
Stoichiometric amounts of Zn salts were used.
sors, solar cells and optoelectronics. Recently, efficient
Friedel–Crafts acylation as well as Beckmann rear-
rangement reactions and a facile synthesis of cyclic
ureas from diamines have been reported using ZnO
[b]
[c]
[d]
[
9]
[e]
catalyst.
Zn(acac) , 10 mol %.
2
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ꢀ 2005 WILEY-VCHVerlag GmbH& Co. KGaA, Weinheim
DOI: 10.1002/adsc.200505011
Adv. Synth. Catal. 2005, 347, 1212–1214

Synthesis of 5-Substituted 1H-Tetrazoles
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Table 2. Nano ZnO-mediated preparation of 5-substituted similarly to provide the corresponding tetrazoles which
[a]
1
H-tetrazoles.
shows that there is no effect of the substitution on ben-
zonitrile (Table 2, entries 2 and 3). Interestingly, phtha-
lonitrile afforded the monoaddition product (Table 2,
entry 4), whereas with Zn(II) salts the diaddition prod-
[
3]
uct is reported in the literature. 4-Formylbenzonitrile
gave only the 1H-tetrazole with the carbonyl (aldehyde)
functionality remaining untouched (Table 2, entry 5). 4-
Chlorophenylacetonitrile provided good yields with a
long reaction time (Table 2, entry 6). Heteroaromatic
nitriles such as 2-pyridinecarbonitrile and cyanopyra-
zine gave the corresponding tetrazoles in shorter reac-
tion times with excellent yields (Table 2, entries 7 and
8).
In conclusion, we have developed a simple and effi-
cient method for the preparation of 5-substituted 1H-
tetrazoles via [2þ3]-cycloaddition using nano ZnO as
a heterogeneous catalyst. Various nitriles reacted with
NaN at 120–1308C to yield the corresponding 5-substi-
3
tuted 1H-tetrazoles with moderate to good yields (69–
82%). The catalyst can be readily recovered and reused.
This methodology may find widespread use in organic
synthesis for the preparation of 5-substituted 1H-tetra-
zoles.
Experimental Section
Typical Procedure for the Preparation of 5-Substituted
1H-Tetrazoles
Nano ZnO (0.1 g) was added to a mixture of benzonitrile
0.257 g, 2.5 mmol) and sodium azide (0.178 g, 2.75 mmol) in
DMF (5 mL) and stirred the mixture was at 1208C for 14 h. Af-
ter completion of reaction (as monitored by TLC), the catalyst
was centrifuged, washed with ethyl acetate and the centrifu-
gate was treated with ethyl acetate (30 mL) and 5 N HCl
[
[
a]
Reaction
conditions:
nitrile
(2.5 mmol),
NaN3
(
(
2.75 mmol), nano ZnO (0.1 g), DMF (5 mL), 120–
308C.
Isolated yields.
1
b]
(
20 mL) and stirred vigorously. The resultant organic layer
was separated and the aqueous layer was again extracted
with ethyl acetate (20 mL). The combined organic layers
were washed with water and concentrated to give the crude sol-
id crystalline 5-phenyltetrazole. Column chromatography was
performed using silica gel (100–200 mesh) to afford pure 5-
tions (Table 1, entries 1–4), in which DMF and NMP
provided better yields. TMSN was also used in the reac-
3
tion with benzonitrile in DMF at 1208C (Table 1, en-
try 5). Various catalysts were screened and it was found
that Nano ZnO is an effective catalyst (Table 1, en-
1
phenyltetrazole; yield: 0.277 g (72%). HNMR (200 M Hz ,
tries 4, 6–8). A control reaction conducted under iden- CDCl /DMSO): d¼8.04 (m, 2H), 7.61 (m, 3H); MS (70 eV):
3
þ
tical conditions but devoid of nano ZnO gave no addi- m/z (%)¼146 (M , 12.65%), 118 (100%), 103 (13.94%), 91
(
36.70%), 77 (30.37%), 63 (26.58%), 39 (17.72%).
tion product, despite prolonged reaction times. Nano
ZnO was recovered quantitatively by simple centrifuga-
tion and reused for three cycles with minimal loss of ac-
tivity (Table 1, entry 4).
Acknowledgements
We chose a variety of structurally divergent benzoni-
triles possessing a wide range of functional groups to un- K. B. S. K and Ch. S thank the CSIR fortheirfellowships.
derstand the scope and the generality of the nano ZnO
promoted [2þ3]-cycloaddition reaction to form 5-sub-
stituted 1H-tetrazoles and the results are summarized
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