Aluminum(III) hydrogensulfate: An efficient solid acid catalyst for the preparation of 5-substituted 1H-tetrazoles

Article abstract of DOI:10.1080/00397911.2010.516861

An efficient method for preparation of 5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitriles and sodium azide is reported using aluminum(III) hydrogensulfate as an effective solid acid. This method has the advantages of good yields, simple methodology, and easy workup. Copyright

Full text of DOI:10.1080/00397911.2010.516861

This article was downloaded by: [Linkopings universitetsbibliotek]
On: 13 June 2013, At: 06:19
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
Aluminum(III) Hydrogensulfate:
An Efficient Solid Acid Catalyst for
the Preparation of 5-Substituted
1H–Tetrazoles
S. Mohammad Sajadi a b , Mehdi Khalaj c , Sayyed Mohammad
Hosseini Jamkarani d , Mehdi Mahame e & Mehrdad Kashefib b
a Department of PetroleumgeoSciences, Faculty of Sciences, Soran
University, Soran, Kurdistan Regional Government, Iraq
b Department of Biology, Faculty of Sciences, Soran University,
Soran, Kurdistan Regional Government, Iraq
c Department of Chemistry, Islamic Azad University, Buinzahra
Branch, Qazvin, Iran
d Department of Chemistry, Islamic Azad University, Karaj Branch,
Karaj, Iran
e Department of Chemistry, Islamic Azad University, Aliabad Katool
Branch, Aliabad Katool, Iran
Published online: 11 Jul 2011.
To cite this article: S. Mohammad Sajadi , Mehdi Khalaj , Sayyed Mohammad Hosseini Jamkarani ,
Mehdi Mahame & Mehrdad Kashefib (2011): Aluminum(III) Hydrogensulfate: An Efficient Solid
Acid Catalyst for the Preparation of 5-Substituted 1H–Tetrazoles, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:20, 3053-3059
To link to this article: http://dx.doi.org/10.1080/00397911.2010.516861
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
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.

The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 3053–3059, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.516861
ALUMINUM(III) HYDROGENSULFATE: AN EFFICIENT
SOLID ACID CATALYST FOR THE PREPARATION OF
5-SUBSTITUTED 1H–TETRAZOLES
S. Mohammad Sajadi,1,2 Mehdi Khalaj,3 Sayyed Mohammad
Hosseini Jamkarani,4 Mehdi Mahame,5 and
Mehrdad Kashefib2
1Department of PetroleumgeoSciences, Faculty of Sciences, Soran
University, Soran, Kurdistan Regional Government, Iraq
2Department of Biology, Faculty of Sciences, Soran University, Soran,
Kurdistan Regional Government, Iraq
3Department of Chemistry, Islamic Azad University, Buinzahra Branch,
Qazvin, Iran
4Department of Chemistry, Islamic Azad University,
Karaj Branch, Karaj, Iran
5Department of Chemistry, Islamic Azad University, Aliabad Katool Branch,
Aliabad Katool, Iran
GRAPHICAL ABSTRACT
Abstract An efficient method for preparation of 5-substituted 1H-tetrazoles via [2 þ 3]
cycloaddition of nitriles and sodium azide is reported using aluminum(III) hydrogensulfate
as an effective solid acid. This method has the advantages of good yields, simple method-
ology, and easy workup.
Keywords Aluminum(III); [2 þ 3] cycloaddition; hydrogensulfate; nitrile; solid acid
catalyst; 5-substituted 1H-tetrazole
INTRODUCTION
The growth of tetrazole chemistry over the past 25 years has been significant,
mainly as a result of the roles played by tetrazoles in coordination chemistry as
ligands, in medicinal chemistry as stable surrogates for carboxylic acids, and in
material applications, including explosives, agriculture, and photography.[1–4]
Received July 6, 2010.
Address correspondence to S. Mohammad Sajadi, Department of PetroleumgeoSciences, Faculty
of Sciences, Soran University, PO Box 862, Soran, Kurdistan Regional Government, Iraq. E-mail:
smohammad.sajadi@gmail.com
3053

3054
S. M. SAJADI ET AL.
Scheme 1. Conversion of nitriles to the corresponding 5-substituted 1H-tetrazoles using Al(HSO4)3..
Another important application of tetrazoles is preparation of imidoylazides.[5] The
conventional method of synthesizing tetrazoles is by addition of azide ions to organic
nitriles or cyanamides.[6] Earlier reported methods for the synthesis of 5-substituted
tetrazoles suffer from drawbacks such as the use of strong Lewis acids or expensive
and toxic metals, and the in situ–generated hydrazoic acid, which is highly toxic and
explosive.[7] Several syntheses of 5-substituted tetrazoles have been reported through
the [2 þ 3] cycloaddition of nitriles using NaN3 or TMSN3 in the presence of
catalysts such as FeCl3–SiO2,[6f] AlCl3,[8] (C2H5)2O ꢀ BF3,[9] tetrabutyl ammonium
fluoride (TBAF),[10] Pd(PPh3)4,[11] Zn=Al hydrotalcite,[12] and ZnO.[13]
The use of solid acid salt catalysts,[14] such as Al(HSO4)3, for synthesizing
organic intermediates and fine chemicals is gaining increasing awareness and is a
field of intense research activity.[15] This salt is a stable and nonhygroscopic solid
material that is insoluble in most organic solvents.
We herein report a new protocol for preparation of 5-substituted 1H-tetrazoles
derivatives from nitriles using aluminum(III) hydrogensulfate as a solid acid catalyst
(Scheme 1).
EXPERIMENTAL
General
All reagents were purchased from Merck and Aldrich and used without further
purification. 13C NMR and 1H NMR spectra were recorded on Brucker 100- and 250-
MHz instruments using tetramethylsilane (TMS) as an internal standard. Chemical
shifts are reported in parts per million (ppm), and coupling constants are reported
in hertz (Hz). Infrared (IR) spectra were recorded on a Shimadzu 470 spectrophot-
ometer. Thin-layer chromatography (TLC) was performed on Merck precoated
silica-gel 60-F254 plates. Al(HSO4)3 was prepared from AlCl3 and H2SO4, according
to the literature.[14c,15] Massah and coworkers studied the characterization of the
Al(HSO4)3 using DSC, TG-DTG, and FT–IR spectroscopy.[15b]
General Procedure for Preparation of 5-Substituted 1H-Tetrazoles
Al(HSO4)3(10 mol%) was added to a mixture of nitrile (2 mmol), NaN3
(3 mmol), and distilled dimethylformamide (6 mL) and stirred at 120 ꢁC for the appro-
priate time (Table 1). After completion of the reaction (as monitored by TLC), the
mixture was cooled to room temperature. The solid acid was filtered, and the filtrate
was treated with ethyl acetate (35 mL) and 5 N HCl (20 mL) and stirred vigorously.
The resultant organic layer was separated, and the aqueous layer was again extracted
with ethyl acetate (25 mL). The combined organic layer was washed with water (8 mL)

5-SUBSTITUTED 1H–TETRAZOLE
3055
Table 1. Synthesis of various 5-substituted 1H-tetrazoles in the presence of Al(HSO4)3 by reaction of
sodium azide and nitriles at 120 ꢁC
Time
(h)
Yield
(%)a
Entry
1
Substrate
Product
Ref.
6f
18
18
91
87
2
6f
3
4
5
18
18
18
85
90
89
6f
6f
6f
6
7
18
18
90
84
6f
6f
8
9
22
36
18
85
60
84
17
18
6f
10
(Continued )

3056
S. M. SAJADI ET AL.
Table 1. Continued
Time
(h)
Yield
(%)a
Entry
11
Substrate
Product
Ref.
6f
18
30
85
69
12
17
aYields refer to the pure isolated products.
and concentrated to give a crude product. Column chromatography using silica gel
gave pure product in excellent yield. The pure products were characterized by
IR and NMR. All the products are known compounds, and the spectral data and
melting points were identical to those reported in the literature.
RESULTS AND DISCUSSION
The general synthetic method is depicted in Scheme 1. 5-Substituted 1H-
tetrazoles were obtained from the reaction of nitrile with sodium azide in the
presence of Al(HSO4)3 as a solid acid catalyst at 120 ꢁC for appropriate time in good
yields, as summarized in Table 1.
First, we optimized the amount of Al(HSO4)3 catalyst required in the reaction
between benzonitrile and sodium azide (Table 2). Water was not a suitable solvent for
this reaction. Not many organic solvents are stable at the high temperatures necessary
for cycloaddition reactions (sometimes as high as 130 ꢁC), and for this reason
dimethylformamide (DMF) is most commonly used for this purpose.[2a,9,12] The opti-
mum amount of Al(HSO4)3 was found to be 10 mol% in the presence of nitrile
(2 mmol) and sodium azide (3 mmol) in DMF (6 mL). We next examined a variety
of structurally divergent benzonitriles possessing a wide range of functional groups
to understand the scope and generality of the Al(HSO4)3-promoted [2 þ 3] cycloaddi-
tion reaction to form 5-substituted 1H-tetrazoles, and the results are summarized in
Table 1. The nature of the substituent on the benzonitrile did not affect the reaction
time (Table 1, entries 1–7, 10, and 11). Reactions of the 3-methylbenzonitrile (Table 1,
entry 8) and 4-hydroxybenzonitrile (Table 1, entry 9) were complete at 120 ꢁC after 22
and 36 h, respectively, and gave the corresponding tetrazole in excellent yields.
The products were characterized by IR, 1H NMR, and 13C NMR spectroscopy
and from melting points. The disappearance of one strong and sharp absorption
band (CN stretching band) and the appearance of an NH stretching band in the IR
spectra were evidence for the formation of 5-substituted 1H-tetrazoles. 13C NMR
spectra display signals for tetrazole ring carbons of arylaminotetrazoles in the
range of 154–157 ppm (depending on the nature of the substituents in the amino
functionality).[16]

5-SUBSTITUTED 1H–TETRAZOLE
3057
Table 2. Preparation of 5-phenyltetrazole using varying amounts of
Al(HSO4)3 under thermal conditions at 120 ꢁCa
Entry
Al(HSO4)3 (mol%)
Solvent
Yield%b
1
2
3
4
5
6
5
7
DMF
DMF
DMF
DMSO
DMF
DMF
54
76
93
91
94
0c
10
10
15
0
aReaction conditions: nitrile (2 mmol), NaN3 (3 mmol), Al(HSO4)3
(10 mol%), and DMF, (6 mL), reaction time (18 h) at 120 ꢁC.
bIsolated yield.
cIn the absence of catalyst at 120 ꢁC, no reaction occurred after 18 h.
CONCLUSION
In conclusion, we have developed a novel and highly efficient method for the
synthesis of various 5-substituted 1H-tetrazoles by treatment of nitriles with sodium
azide in the presence of Al(HSO4)3 as an effective catalyst. The significant advantages
of this methodology are good yields, elimination of dangerous and harmful hydrazoic
acid, simple workup procedure, and easy preparation and handling of the catalyst.
ACKNOWLEDGMENT
The authors acknowledge the financial support by the Soran University.
REFERENCES
1. Bulter, R. N. In Comprehensive Heterocyclic Chemistry II; A. R. Katritzky, C. W. Ress,
E. F. V. Scriven, (Eds.); Pergamon: New York, 1996; Vol. 4, p. 621.
2. (a) Herr, R. 5-Substituted-1H-tetrazoles as carboxylic acid isosteres: Medicinal chemistry
and synthetic methods. J. Bioorg. Med. Chem. 2002, 10, 3379–3393; (b) Holland, G. F.;
Pereira, J. N. Heterocyclic tetrazoles, a new class of lipolysis inhibitors. J. Med. Chem.
1967, 10, 149–154; (c) Figdor, S. K.; Schach von Wittenau, M. Metabolism of
5-(3-pyridyl)tetrazole. J. Med. Chem. 1967, 10, 1158–1159; (d) Rhonnstad, P.; Wensbo,
D. On the relative strength of the 1H- tetrazol-5-yl- and the 2-(triphenylmethyl)-2H-
tetrazol-5-yl-group in directed ortho-lithiation. Tetrahedron Lett. 2002, 43, 3137–3139.
3. Klapo¨tke, T. M.; Stierstorfer, J.; Weber, B. New energetic material: Synthesis and char-
acterization of copper 5-nitriminotetrazolates. Inorg. Chim. Acta. 2009, 362, 2311–2320.
4. John, E. O.; Kirchmeier, R. L.; Shreeve, J. M. Reactions of 5-(perfluoro-alkyl)tetrazolates
with Cyanogen, Nitrosyl, and Cyanuric Chlorides. Inorg. Chem. 1989, 28, 4629.
5. Modarresi-Alam, A. R.; Khamooshi, F.; Rostamizadeh, M.; Keykha, H.;
1
Nasrollahzadeh, M.; Bijanzadeh, H. R.; Kleinpeter, E. Dynamic H NMR spectroscopic
study of the restricted S-N rotation in aryl-N-(arylsulfonyl)-N- (triphenylphosphoranyli-
dene)imidocarbamates. J. Mol. Struc. 2007, 841, 61–66.
6. (a) Kadaba, P. K. Role of protic and dipolar aprotic solvents in heterocyclic syntheses via
1,3-dipolar cycloaddition reactions. Synthesis 1973, 71–84; (b) Wittenberger, S. J. Recent
developments in tetrazole chemistry: A review. Org Prep. Proc. Int. 1994, 26, 499–532;

3058
S. M. SAJADI ET AL.
(c) Curran, D. P.; Hadida, S.; Kim, S. Y. Tris(2-perfluorohexylethyl)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. A new method for the preparation of tetrazoles from nitriles using
trimethylsilylazide=trimethylaluminum. Tetrahedron Lett. 1993, 34, 8011–8014; (e)
Modarresi-Alam, A. R.; Nasrollahzadeh, M. Synthesis of 5-arylamino- 1H(2H)-tetrazoles
and 5-amino-1-aryl-1H-tetrazoles from secondary arylcyanamides in glacial acetic acid: A
simple and efficient method. Turk. J. hem. 2009, 33, 1–14; (f) Nasrollahzadeh, M.; Bayat,
Y.; Habibi, D.; Moshaee, S. FeCl3–SiO2 as a reusable heterogeneous catalyst for the syn-
thesis of 5-substituted 1H-tetrazoles via [2 þ 3] cycloaddition of nitriles and sodium azide.
Tetrahedron Lett. 2009, 50, 4435–4438; (g) Nasrollahzadeh, M.; Habibi, D.; Shahkarami,
Z.; Bayat, Y. A general synthetic method for the formation of arylaminotetrazoles using
natural natrolite zeolite as a new and reusable heterogeneous catalyst. Tetrahedron 2009,
65, 10715–10719; (h) Habibi, D.; Nasrollahzadeh, M.; Faraji, A. R.; Bayat, Y. Efficient
synthesis of arylaminotetrazoles in water. Tetrahedron 2010, 66, 3866–3870.
7. (a) Duncia, J. V.; Pierce, M. E.; Santella III, J. B. 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; (b) Sisido, K.; Nabika, K.; Isida, T.; Kozima, S. Forma-
tion of organotin–nitrogen bonds, III: N-Trialkyltin-5-substituted tetrazoles. J. Organo-
met. Chem. 1971, 33, 337–346; (c) Carini, D. J.; Duncia, J. V.; Aldrich, P. E.; Chui, A.
T.; Johnson, A. L.; Pierce, M. E.; Price, W. A.; Santella III, J. B.; Wells, G. J.; Wexler,
R. R.; Wong, P. C.; Yoo, S.-E.; Timmermans, P. B. M. W. M. Nonpeptide angiotensin
II receptor antagonists: The discovery of a series of N-(biphenylylmethyl)imidazoles as
potent, orally active antihypertensives. J. Med. Chem. 1991, 34, 2525–2547; (d)
Wittenberger, S. J.; Donner, B. G. Dialkyltin oxide–mediated addition of trimethylsilyl
azide to nitriles: A novel preparation of 5-substituted tetrazols. J. Org. Chem. 1993, 58,
4139–4144.
8. Matthews, D. P.; Green, J. E.; Shuker, A. J. Parallel synthesis of alkyl tetrazole derivatives
using solid support chemistry. J. Comb. Chem. 2000, 2, 19–23.
9. Kumar, A.; Narayanan, R.; Shechter, H. Rearrangement reactions of (hydroxyphenyl)-
carbenes. J. Org. Chem. 1996, 61, 4462–4465.
10. 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.
11. Gyoung, Y. S.; Shim, J.-G.; Yamamoto, Y. Regiospecific synthesis of 2-allylated-5-substi-
tuted tetrazoles via palladium-catalyzed reaction of nitriles, trimethylsilyl azide, and allyl
acetates. Tetrahedron Lett. 2000, 41, 4193–4196.
12. Kantam, M. L.; Shiva Kumar, K. B.; Phani Raja, K. An efficient synthesis of 5-substituted
1H-tetrazoles using Zn=Al hydrotalcite catalyst. J. Mol. Catal. A: Chem. 2006, 247,
186–188.
13. Kantam, M. L.; Shiva Kumar, K. B.; Sridhar, C. Nanocrystalline ZnO as an efficient
heterogeneous catalyst for the synthesis of 5-substituted 1H-tetrazoles. Adv. Synth. Catal.
2005, 347, 1212–1214.
14. (a) Modarresi-Alam, A. R.; Nasrollahzadeh, M.; Khamooshi, F. Solvent-free preparation
of primary carbamates using silica sulfuric acid as an efficient reagent. Arkivoc 2007, 16,
238–245; (b) Modarresi-Alam, A. R.; Khamooshi, F.; Nasrollahzadeh, M.; Amirazizi, H.
A. Silica-supported perchloric acid (HClO4–SiO2): An efficient reagent for the preparation
of primary carbamates under solvent-free conditions. Tetrahedron 2007, 63, 8723–8726; (c)
Modarresi-Alam, A. R.; Nasrollahzadeh, M.; Khamooshi, F. Al(HSO4)3 as an efficient
reagent for the preparation of primary carbamates under solvent-free conditions. Sci.
Iranica 2008, 15, 452–455.

5-SUBSTITUTED 1H–TETRAZOLE
3059
15. (a) Ghorbani-Choghamarani, A.; Zeinivand, J. Catalytic oxidation of sulfides to sulfox-
ides using aluminium hydrogen sulfate, sodium nitrite, and catalytic amounts of metal
bromide. J. Iran. Chem. Soc. 2010, 7, 190–194; (b) Massah, A. R.; Asadi, B.; Hoseinpour,
M.; Molseghi, A.; Javad Kalbasi, R.; Javaherian Naghash, H. A novel and efficient
solvent-free and heterogeneous method for the synthesis of primary, secondary, and
bis-N-acylsulfonamides using metal hydrogen sulfate catalysts. Tetrahedron 2010, 65,
7696–7705.
16. Goljer, I.; Svetlik, J.; Hrusovsky, I. 13C-NMR of substituted tetrazoles. Monatsh. Chem.
1983, 114, 65–70.
17. Mihina, J. S.; Herbst, R. M. The reaction of nitriles with hydrazoic acid: Synthesis of
monosubstituted tetrazoles. J. Org. Chem. 1950, 15, 1082–1092.
18. Demko, P. Z.; Sharpless, K. B. Preparation of 5-substituted 1H-tetrazoles from nitriles in
water. J. Org. Chem. 2001, 66, 7945–7950.