Iodine-catalyzed, efficient, one-pot protocol for the conversion of araldehydes into 5-aryl-1H-tetrazoles

Article abstract of DOI:10.1080/00397911.2010.497593

An easy access to various 5-aryl-1H-tetrazoles by a one-pot direct conversion of aldehydes to tetrazoles without the isolation of the intermediate nitriles using commercially available iodine as a catalyst is described. The protocol offers advantages in terms of good yields, mild reaction conditions, short reaction times, and use of readily available environmentally compatible catalyst. Copyright

Full text of DOI:10.1080/00397911.2010.497593

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Iodine-Catalyzed, Efficient, One-
Pot Protocol for the Conversion of
Araldehydes into 5-Aryl-1H-tetrazoles
M. B. Madhusudana Reddy a & M. A. Pasha a
a Department of Studies in Chemistry, Central College Campus,
Bangalore University, Bengaluru, India
Version of record first published: 20 May 2011.
To cite this article: M. B. Madhusudana Reddy & M. A. Pasha (2011): Iodine-Catalyzed, Efficient, One-
Pot Protocol for the Conversion of Araldehydes into 5-Aryl-1H-tetrazoles, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:14, 2081-2085
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Synthetic Communications1, 41: 2081–2085, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.497593
IODINE-CATALYZED, EFFICIENT, ONE-POT PROTOCOL
FOR THE CONVERSION OF ARALDEHYDES INTO
5-ARYL-1H-TETRAZOLES
M. B. Madhusudana Reddy and M. A. Pasha
Department of Studies in Chemistry, Central College Campus, Bangalore
University, Bengaluru, India
GRAPHICAL ABSTRACT
Abstract An easy access to various 5-aryl-1H-tetrazoles by a one-pot direct conversion of
aldehydes to tetrazoles without the isolation of the intermediate nitriles using commercially
available iodine as a catalyst is described. The protocol offers advantages in terms of good
yields, mild reaction conditions, short reaction times, and use of readily available environ-
mentally compatible catalyst.
Keywords Ammonia; araldehydes; 5-aryl-1H-tetrazoles; iodine; sodium azide
INTRODUCTION
Synthesis of tetrazoles has been a subject of intense investigation because of
their broad application in different scientific research fields.[1,2] Derivatives of tetra-
zoles are useful as antiviral, antibacterial, antifungal, and antituberculous agents.[3a]
In addition to this, tetrazoles are used as catalysts in the synthesis of phosphonates.[3b]
Fang and coworkers used a series of primary alcohols and aldehydes with iodine in
ammonia–water to get the intermediate nitriles, which without isolation were sub-
jected to a [2 þ 3]-cycloaddition reaction with dicyandiamide and sodium azide in
presence of ZnBr2 to afford the corresponding triazines and tetrazoles at reflux[4]
and under microwave irradiation.[5] These method suffer from long reaction times
and harsh reaction conditions. These are the only two methods available in the litera-
ture for this one-pot, two-step synthesis of tetrazoles from aldehydes. Thus develop-
ment of a catalytic synthetic method for the preparation of tetrazoles still remains an
Received December 15, 2009.
Address correspondence to M. A. Pasha, Department of Studies in Chemistry, Central College
Campus, Bangalore University, Bengaluru 560 001, India. E-mail: m_af_pasha@ymail.com
2081

2082
M. B. MADHUSUDANA REDDY AND M. A. PASHA
Scheme 1. Formation of tetrazole from aldehyde.
active research area, and in continuation of our work on the development of efficient
and environmentally friendly methods for the catalytic synthesis of bioactive molecules
and heterocycles, we have synthesized a number of heterocycles using iodine as
catalyst, few of which include the synthesis of azalactones,[6] a,a0-bis(arylmethylidene)
cycloalkanones,[7] b-acetamido-b-aryl-propiophenones,[8] and xanthenes.[9] Looking
into the utility of iodine as catalyst, its cost, availability, and environmental compati-
bility, we decided to employ iodine alone for the synthesis of tetrazoles from aldehydes
by a one-pot, two-step reaction, without isolating the intermediate nitriles (Scheme 1).
RESULTS AND DISCUSSION
Our investigation began with the evaluation of I2 as reagent for the synthesis of
5-(4-methoxyphenyl)-1H-tetrazole from 4-methoxybenzaldehyde without isolating
the corresponding 4-methoxybenzonitrile at 100 ꢀC in tetrahydrofuran (THF) as a
solvent. The use of 1 equivalent of I2 (for two steps) afforded 73% of the desired
product. Optimization of the reaction condition was undertaken to increase the yield
of the product using different amounts of I2. The yield was increased to 84% using
1 þ 1 ¼ 2 equivalent of I2 under solvent-free conditions. However, the addition of
1 þ 2 or 2 þ 1 equivalents of the I2 did not improve the yield further. We next exam-
ined a wide variety of araldehydes to establish the scope of this transformation. Ara-
ldehydes with electron-withdrawing groups as well as electron-donating substituents
underwent this one-pot conversion to give the corresponding tetrazoles in good yield
(Table 1). In general, the aldehyde was first treated with ammonia–water and THF in
the presence of I2, Once the formation of nitrile was confirmed by thin-layer chroma-
tography (TLC), NaN3 was then added to the same flask to get the corresponding
5-aryl-1H-tetrazoles (3). In all cases, the reactions proceeded efficiently at 100 ꢀC.
Caution: Use of excess ammonia in combination with sodium azide or iodine in
the following procedure should be avoided because of the release of traces of hazard-
ous hydrazoic acid or nitrogen triiodide monoamine.[10,11]
EXPERIMENTAL
All chemicals used were commercial and all solvents were distilled before use.
Reactions were monitored on TLC by comparison with the authentic samples. Melting
points were determined on a Buchi melting-point apparatus. The products were char-
¨
acterized by comparison of their physical data with those of known samples or by

ONE-POT SYNTHESIS OF 5-ARYL-1H-TETRAZOLES
2083
Yield (%)b,c
90
Table 1. Synthesis of tetrazoles from aromatic aldehydes using molecular iodine
Entry
a
Aldehyde (1)
Tetrazole (3)a
Time (h)
8
b
12
89
c
8
85
79
d
10
e
f
9
84
79
8.5
g
7
81
67
h
8
7
i
90
(Continued )

2084
M. B. MADHUSUDANA REDDY AND M. A. PASHA
Table 1. Continued
Entry
j
Aldehyde (1)
Tetrazole (3)a
Time (h)
Yield (%)b,c
12
65
k
8.5
73
aAll reactions were performed using an aldehyde (5 mmol), sodium azide (6 mmol), and I2 (2equivalents).
bIsolated yield.
cAll the products are known, and physical properties agree with the literature values.
1
comparison of their infrared (IR), H NMR, gas chromatography (GC)–mass, and
liquid chromatography (LC)–mass spectra. The IR and 1H NMR spectra of the pro-
ducts were recorded on Shimatzu Fourier transform (FT)–IR 8400 and Bruker AMX
(400-MHz) spectrometers respectively. GC-MS analysis was performed on a Shimatzu
QP5050A series instrument. Yields refer to the isolated yields of the products.
General Procedure for the Preparation of 5-Substituted 1H-Tetrazole
A mixture of an appropriate aldehyde (1, 5 mmol), iodine (5 mmol), liquid
ammonia (5 mmol, 28% solution), and THF (5 mL) was stirred at room temperature
for about 1 h. When the dark solution became colorless, NaN3 (6 mmol) and iodine
(5 mmol) were then added, and the reaction mixture was heated to 100 ꢀC for 7–12 h
with vigorous stirring. The crude reaction mixture was transferred into a separating
funnel, and ethyl acetate (50 mL) was added. The pH was adjusted to 1.0 with HCl.
Traces of I2 were removed by washing the organic phase with a sodium thiosulphate
solution (3 ꢁ 10 mL). The organic layer was dried (Na2SO4) and concentrated under
reduced pressure to get pure 5-aryl-1H-tetrazole (3) in 65–90% yield.
CONCLUSION
A facile, convenient, and less hazardous synthetic method for the synthesis of
5-substituted-1H-tetrazoles in good yields and high purity from various araldehydes
is achieved. This method offers several advantages including mild reaction conditions,
low catalyst loading, and no isolation of the intermediate. In addition, our process
involves use of one environmentally benign, cheap, and easy-to-handle catalyst.
ACKNOWLEDGMENT
One of the authors, M. B. Madhusudana Reddy, thanks Mr. Narayana Reddy,
teacher, Government Primary School, Hemavathi, Madakasira, A. P., India, for
constant encouragement.

ONE-POT SYNTHESIS OF 5-ARYL-1H-TETRAZOLES
2085
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