Antimony trioxide as an efficient Lewis acid catalyst for the synthesis of 5-substituted 1H-tetrazoles

Article abstract of DOI:10.1080/00397910802378381

Sb₂O₃ was found to be effective as a catalyst for a smooth (2 + 3) cycloaddition of sodium azide with nitriles to afford 5-substituted 1H-tetrazoles in good yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802378381

This article was downloaded by: [University of Sussex Library]
On: 23 July 2013, At: 01:02
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Antimony Trioxide as an
Efficient Lewis Acid Catalyst
for the Synthesis of 5-
Substituted 1H-Tetrazoles
G. Venkateshwarlu a , K. C. Rajanna a & P. K.
Saiprakash a
a Department of Chemistry, Osmania University,
Hyderabad, India
Published online: 08 Jan 2009.
To cite this article: G. Venkateshwarlu , K. C. Rajanna & P. K. Saiprakash (2009)
Antimony Trioxide as an Efficient Lewis Acid Catalyst for the Synthesis of 5-
Substituted 1H-Tetrazoles, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:3, 426-432, DOI:
10.1080/00397910802378381
To link to this article: http://dx.doi.org/10.1080/00397910802378381
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and

are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communications1, 39: 426–432, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802378381
Antimony Trioxide as an Efficient Lewis Acid
Catalyst for the Synthesis of 5-Substituted
1H-Tetrazoles
G. Venkateshwarlu, K. C. Rajanna, and P. K. Saiprakash
Department of Chemistry, Osmania University, Hyderabad, India
Abstract: Sb2O3 was found to be effective as a catalyst for a smooth (2 þ 3)
cycloaddition of sodium azide with nitriles to afford 5-substituted 1H-tetrazoles
in good yields.
Keywords: Sb2O3, sodium azide, 5-substituted 1H-tetrazoles
INTRODUCTION
Tetrazoles, a class of heterocycles, received considerable attention because
of their wide range of applications in pharmaceuticals as lipophilic
spacers and carboxylic acid surrogates and in speciality explosives, pho-
tography, and information recording systems.[1] They are important
ligands for many useful transformations and also precursors for a variety
of nitrogen-containing heterocycles.[2] Losartan, irbesartan, candesartan,
and valsartan are famous antihypertensive drugs belonging to the class of
nonpeptide angiotensin-II inhibitors, which prevent increases in blood
pressure; they have biphenyl tetrazolyl moiety in their structure. Deriva-
tives of tetrazoles are also used for biological activities such as antiviral,
antibacterial, antifungal, and antituberculous activities. In addition to
this, tetrazoles are used as catalysts in the synthesis of phosphonates.
Conventionally 5-substituted 1H-tetrazoles are synthesized via (2 þ 3)
cycloaddition of an azide and a nitrile.[3] The reagents used in the basic
method are highly toxic and expensive and are also water sensitive. In
Received April 24, 2008.
Address correspondence to K. C. Rajanna, Department of Chemistry, Osmania
University, Hyderabad, India. E-mail: kcrajannaou@rediffmail.com
426

Synthesis of Tetrazoles
427
addition to this, hydrazoic acid is not only highly toxic and explosive but
also volatile. To overcome the drawbacks of the earlier methods, atten-
tion has been paid to developing safer and neat methods for the synthesis
of tetrazoles. Accordingly 5-substituted tetrazoles are also prepared
through the reaction of sodium azide with corresponding nitriles in the
presence of an amine salt.[4] Demko and Sharpless and coworkers rep-
orted an innovative and safe procedure for the synthesis of tetrazoles
by the addition of sodium azide to nitriles using stoichiometric amounts
of Zn(II) salts in water.[5] Amantini et al. efficiently synthesized tetrazoles
by the addition of TMSN3 (trimethyl silyl azide) to organic nitriles using
10 mol% TBAF (tetra butyl ammonium fluoride) as catalyst.[6] Su et al.[7]
reported a series of 1-substituted 1H-1,2,3,4-tetrazole compounds that
have been synthesized in good yields from amines, triethyl orthofor-
mate, and sodium azide through the catalyzed reaction with Yb(OTf)3.
A series of primary alcohols and aldehydes were treated with iodine in
ammonia water under microwave irradiation to give the intermediate
nitriles, which without isolation underwent [2 þ 3] cycloaddition with
dicyandiamide and sodium azide to afford the corresponding triazines
and tetrazoles in high yields.[8] Katritzky and coworkers[9] suggested a
general method for the synthesis of 1,5-disubstituted tetrazoles from
imidoylbenzotriazoles under mild reaction conditions and shorter reac-
tion times. A versatile and highly efficient Zn(OTf)2-mediated one-pot
synthesis of 1,5-disubstituted tetrazoles derivatives has been achieved
by Hajra et al.[10] from alkenes, N-bromo succinimide (NBS), nitriles, and
TMSN3. In recent publications,[11,12] Lakshmi Kantam et al. developed
simple and efficient methods for the preparation of 5-substituted 1H-
tetrazoles via [2 þ 3] cycloaddition using nano ZnO and zinc hydroxy-
apatite (ZnHAP) as effective catalysts.
Antimony compounds are excellent catalysts to accelerate the poly-
merization in polyester manufacturing. Even though antimony trioxide is
the most widely used polymerization catalyst, to the best of our knowledge,
Sb2O3 has not been explored as a catalyst for such a transformation pre-
viously. In this communication, we report the synthesis of 5-substituted
1H-tetrazoles from a wide variety of organic nitriles with sodium azide
using Sb2O3 as a Lewis acid catalyst for the first time (Scheme 1).
Scheme 1. Synthesis of 5-substituted 1H-tetrazoles catalyzed by Sb2O3.

428
G. Venkateshwarlu, K. C. Rajanna, and P. K. Saiprakash
In an effort to develop a better catalytic system, various reaction
parameters were screened for [2 þ 3] cycloaddition of benzonitrile with
sodium azide to yield 5-phenyltetrazole and are presented in Table 1. The
solvent has a pronounced effect in these reactions (Table 1, entries 1–4), in
which dimethyl formamide (DMF) was proved to be the best solvent to give
good yields of corresponding tetrazole, whereas dimethyl sulfoxide (DMSO)
and NMP provided moderate yields, and water gave poor yields of 5-phenyl-
tetrazole. TMSN3 is also used in the reaction with benzonitrile in DMF at
120 ꢀC (Table 1, entry 5).
To understand the scope and limitations of Sb2O3-catalyzed [2 þ 3]
cycloaddition reaction, various structurally divergent benzonitriles
possessing a wide range of functional groups were reacted with sodium azide
to give corresponding tetrazoles, and the results are summarized in Table 2.
The various nitriles tested are aromatic, heteroaromatic, and aliphatic; the
aromatic benzonitriles gave moderate to good yields (Table 2, entries
1–14). 4-Chlorobenzonitriles provided the corresponding tetrazoles with
good yield, whereas 2-chlorobenzonitriles gave slightly less yield compared
to its para counterpart. This might be due to a more pronounced steric effect
of chloro group at the orthoposition (Table 2, entries 2 and 3). Benzonitriles
with electron-donating groups such as 4-methoxy benzonitrile and 4-methyl
benzonitrile afforded slightly better yields (Table 1, entries 8 and 9) com-
pared with electron-withdrawing groups such as hydroxy, chloro, cyano,
bromo, and formyl groups present on the aromatic ring (Table 1, entries
2–7). 4-Formylbenzonitrile gave only 1H-tetrazole with carbonyl (aldehyde)
functionality untouched (Table 2, entry 4). 1,4-Dicyanobenzene afforded di-
addition product (Table 2, entry 7). Aliphatic nitriles such as 4-chlorophenyl
Table 1. Screening of reaction parameters for the formation
5-phenyltetrazolea
Entry
Solvent
Azide
Yield (%)b
1
2
3
4
5
Water
DMF
DMSO
NMP
NaN3
NaN3
NaN3
NaN3
TMSN3
39
86
72
69
79
DMF
aReaction conditions: nitrile (1 mmol), NaN3 (2 mmol), Sb2O3
(0.029 g or 0.1 mmol), DMF (5 mL), reaction time (8 h), 120 ꢀC.
bIsolated yields.

Synthesis of Tetrazoles
429
Table 2. Preparation pf 5-substituted 1H-tetrazoles mediated by Sb2O3
Entry
1
Substrate
Temp (ꢀC)
120
Time (h)
8
Yield (%)
86
2
3
4
5
6
7
8
9
120
120
120
120
130
130
120
120
8
10
8
87
81
79
85
71
79
85
8
10
9
8
8
86
(Continued)

430
G. Venkateshwarlu, K. C. Rajanna, and P. K. Saiprakash
Table 2. Continued
Entry
10
Substrate
Temp (ꢀC)
120
Time (h)
4
Yield (%)
88
11
12
13
14
120
130
130
130
4
20
20
18
82
71
69
78
acetonitrile, phenyl acetonitrile, and (phenylsulfonyl) acetonitrile provided
moderate yields of corresponding tetrazoles with long duration of time
(Table 2, entries 12–14). Heteroaromatic nitriles such as 2-pyridinecarbo-
nitrile and cyanopyrazine gave the corresponding tetrazoles in shorter
reaction times with excellent yields (Table 2, entries 10 and 11).
In conclusion, a simple and efficient method was developed for the
preparation of 5-substituted 1H-tetrazoles via (2 þ 3) cycloaddition using
an economically cheap Sb2O3 catalyst. Various structurally divergent
nitriles were reacted with NaN3 at 120–130 ꢀC to yield the corresponding
5-substituted 1H-tetrazoles with moderate to good yields. This metho-
dology may find widespread use in organic synthesis for the preparation
of 5-substituted 1H-tetrazoles.
EXPERIMENTAL
Typical Procedure for Preparation of 5-Substituted 1H-Tetrazole
Sb2O3 was added (0.029 g or 0.1 mmol) to a mixture of benzonitrile
(0.103 g or 1 mmol), sodium azide (0.130 g or 2 mmol) in DMF (5 mL)

Synthesis of Tetrazoles
431
and stirred at 120 ꢀC for 12 h. After completion of reaction (as monitored
by thin-layer chromatography, TLC), the reaction mixture was treated
with ethyl acetate (30 mL) and washed with distilled water, and then
the organic layer was treated with 5 N HCl (20 mL) and stirred vigor-
ously. 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 solid
crystalline 5-phenyltetrazole. Column chromatography was performed
using silica gel (100–200 mesh) to afford pure 5-phenyltetrazole.
1H NMR (200 MHz, CDCl3 þ DMSO) d 8.04 (m, 2H), 7.61 (m, 3H);
MS (70 eV) m=z (%) 146 (Mþ, 12.65%), 118 (100%), 103 (13.94%), 91
(36.70%), 77 (30.37%), 63 (26.58%), 39(17.72%).
ACKNOWLEDGMENTS
The authors sincerely thank Dr. M. Lakshmi Kantham for constant
encouragement and helpful discussions.
REFERENCES
1. (a) Butler, R. N. In Comprehensive Heterocyclic Chemistry; A. R. Katritzky,
C. W., Rees, and E. F. V. Scriven (Eds.); Pergamon: Oxford, U.K., 1996; vol.
4; (b) Singh, H.; Chala, A. S.; Kapoor, V. K.; Paul, D.; Malhotra, R. K.
Medicinal chemistry of tetrazoles. Prog. Med. Chem.. 1980, 17, 151; (c)
Ostrovskii, V. A.; Pevzner, M. S.; Kofmna, T. P.; Sheherbinin, M. B.;
Tselinskii, I. V. Energetic 1,2,4-triazoles and tetrazoles synthesis, structure,
and properties. Targets Heterocycl. Syst. 1999, 3, 467; (d) Hiskey, M.;
Chavez, D. E.; Naud, D. L.; Son, S. F.; Berghout, H. L.; Bome, C. A. Pro-
gress in high-nitrogen chemistry in explosives, propellants, and pyrotechnics.
Proc. Int. Pyrotech. Semin. 2000, 27, 3.
2. Huisgen, R.; Sauer, J.; Sturm, H. J.; Markgraf, J. H. Ringoffnungen der
azole, II: Die bildung von 1.3.4-oxdiazolen bei der acylierung 5-substituierter
Tetrazole. Chem. Ber. 1960, 93, 2106–2124.
3. (a) Wittenberger, S. J. Recent development in tetrazole chemistry: A review.
Org. Prep. Proced. Intl. 1994, 26, 499; (b) Dunica, J. V.; Pierce, M. E.; Santella,
J. B. III. Three synthetic routes to a sterically hindered tetrazole: A new
one-step mild conversion of an amide into a tetrazole. J. Org. Chem. 1991,
56, 2395–2400; (c) Curran, D. P.; Hadida, S.; Kim, S. Y. tris-(2-Perflurohexy-
lethyl)tin azide: A new reagent for preparation of 5-substituted tetrazoles
from nitriles with purification by fluorous=organic liquid–liquid extraction.
Tetrahedron 1999, 55, 8997–9006; (d) Huff, B. E.; Staszak, M. A new method
for the preparation of tetrazoles from nitriles using trimethylsilyazide=
trimethylaluminum. Tetrahedron Lett.. 1993, 34, 8011–8014; (e) Kumar, A.;

432
G. Venkateshwarlu, K. C. Rajanna, and P. K. Saiprakash
Narayanan, R.; Shechter, H. Rearrangement reactions of (hydroxyphenyl)-
carbenes. J. Org. Chem. 1996, 61, 4462–4465.
4. Koguro, K.; Ora, T.; Mitsui, S.; Orita, P. Novel synthesis of 5-substituted
tetrazoles from nitriles. Synthesis 1998, 6, 910–914.
5. (a) Demko, Z. P.; Sharpless, K. B. Preparation of 5-substituted 1H-tetrazoles
from nitriles in water. J. Org. Chem. 2001, 66, 7945–7950; (b) Himo, F.;
Demko, Z. P.; Noodleman, L.; Sharpless, K. B. Mechanisms of tetrazole
formation by addition of azide to nitriles. J. Am. Chem. Soc. 2002, 124,
12210–12216; (c) Himo, F.; Demko, Z. P.; Noodleman, L.; Sharpless, K. B.
Why is tetrazole formation by addition of azide to organic nitriles catalyzed
by zinc(II) salts? J. Am. Chem. Soc. 2003, 125, 9983–9987.
6. Amantini, D.; Beleggia, R.; Fringuelli, F.; Pizzo, F.; Vaccoro, L. TBAF-
catalyzed synthesis of 5-substituted 1H-tetrazoles under solventless conditions.
J. Org. Chem. 2004, 69, 2896–2898.
7. Su, W. K.; Hong, Z.; Shan, W. G.; Zhang, X. X. A facile synthesis of
1-substituted 1H-1,2,3,4-tetrazoles catalyzed by ytterbium triflate hydrate.
Eur. J. Org. Chem. 2006, 2723–2726.
8. Shie, J. J.; Fang, J. M. Microwave-assisted one-pot tandem reactions
for direct conversion of primary alcohols and aldehydes to triazines and
tetrazoles in aqueous media. J. Org. Chem. 2007, 72, 3141–3144.
9. Katritzky, A. R.; Cai, C.; Meher, N. K. Efficient synthesis of
1,5-disubstituted tetrazoles. Synthesis 2007, 1204–1208.
10. Hajra, S.; Sinha, D.; Bhowmick, M. Metal triflate catalyzed reactions of
alkenes, NBS, nitriles, and TMSN3: Synthesis of 1,5-disubstituted tetrazoles.
J. Org. Chem. 2007, 72, 1852–1855.
11. Lakshmi Kantam, M.; Shiva Kumar, K. B.; Sridhar, C. Nanocrystalline
ZnO as an efficient hetrogeneous catalyst for the synthesis of 5-substitued
1H-tetrazoles. Adv. Synth. Catal. 2005, 347, 1212–1214.
12. Lakshmi Kantam, M.; Balasubramanyam, V.; Shiva Kumar, K. B. Zinc
hydroxyapatite–catalyzed efficient synthesis of 5-substituted 1H-tetrazoles.
Synth. Commun. 2006, 36, 1809–1814.