Synthesis of 5-Substituted Tetrazoles from Nitriles Catalyzed by Sulfamic Acid

Full text of DOI:10.1080/00304948.2017.1342510

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: http://www.tandfonline.com/loi/uopp20
Synthesis of 5-Substituted Tetrazoles from Nitriles
Catalyzed by Sulfamic Acid
Abbas Aminimanesh & Safora Shirian
To cite this article: Abbas Aminimanesh & Safora Shirian (2017) Synthesis of 5-Substituted
Tetrazoles from Nitriles Catalyzed by Sulfamic Acid, Organic Preparations and Procedures
International, 49:4, 346-354, DOI: 10.1080/00304948.2017.1342510
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Date: 23 August 2017, At: 10:03

Organic Preparations and Procedures International, 49:346–354, 2017
Copyright Ó Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2017.1342510
Synthesis of 5-Substituted Tetrazoles from Nitriles
Catalyzed by Sulfamic Acid
Abbas Aminimanesh and Safora Shirian
Department of Chemistry, Payame Noor University, P. O. Box 19395-3697,
Tehran, Iran
Tetrazoles are five-membered heterocyclic compounds1 and, though not generally
found in nature2 possess interesting applications in pharmaceuticals,2 agriculture,3–5
photography6 and as components of explosives.7 The tetrazole ring is employed as a
metabolically-stable carboxylic acid isostere in medicinal chemistry.8 Tetrazole deriv-
atives have a wide range of applications in coordination chemistry as nitrogen-con-
taining heterocyclic ligands as well as in the preparation of imidoyl azides.9 They
are also used as plant growth regulators,7 herbicides, and fungicides8 and possess
anti-allergic,9 antibiotic,10,11 CCK-B antagonist,12 anti-hypertensive,13 and anti-viral
activities.14 Recently, compounds incorporating the tetrazole motif have been widely
utilized for binding of aryl thiotetrazolylacetanilides with HIV-1 reverse transcrip-
tase.15 This broad range of usefulness has elicited significant effort toward the prepa-
ration of tetrazoles.2–7
The most common synthetic method for the 5-substituted tetrazoles involves the
[3C2] cycloaddition of an azide with a nitrile.16 The reaction has been carried out
using numerous catalysts such as BiCl3,17 copper triflates,18 CdCl2,19 Fe(OAc)2,20
ZnBr2,21 triethylamine hydrochloride,22 Bronsted acid catalysts,23 various Lewis acid
catalysts such as AlCl3,24 BF3-OEt2,25 FeCl3,26 n-Bu4NF,27 InCl3,28 I2,29
(CH3)2SnO30 and by using some heterogeneous catalysts such as NaHSO4 SiO2,29
.
CoY zeolites,31 Zn/Al hydrotalcite,32 nanocrystalline ZnO,33 mesoporous ZnS nano-
spheres,34 Zn hydroxyapatite,35 Pd(PPh3)4,36 Cu2O,37 and CuFe2O4 nanoparticles.38
The reaction of phenyl isocyanide with N-halosuccinimides in the presence of azide
ion under phase-transfer catalyzed (PTC) conditions has led to a simple and facile
synthesis of the corresponding 5-halo-1-phenyltetrazoles.39 Acid catalysts are also
employed for the synthesis of tetrazoles via addition of isocyanides to hydrazoic
acid.40 Some of these known methods suffer from drawbacks such as drastic reaction
conditions, low yields, use of expensive moisture-sensitive reagents, the need to use
stoichiometric amounts of catalyst, formation of side-products, toxic metal catalysts,
tedious work-up, or complex isolation and recovery procedures; in addition, hydra-
zoic acid is toxic, volatile, and explosive.30 Thus, there is still a need to develop
new catalytic, environmentally benign and efficient protocols for the preparation of
Received November 20, 2016; in final form February 27, 2017.
Address correspondence to Abbas Aminimanesh, Department of Chemistry, Payame Noor
University, P. O. Box 19395-3697, Tehran, Iran. E-mail: a_aminima@yahoo.com
346

Synthesis of 5-Substituted Tetrazoles
347
tetrazoles. We report herein the synthesis of 5-substituted tetrazoles by the addition
of sodium azide to nitriles in DMF using sulfamic acid (H2NSO3H) as a solid acid
catalyst (Scheme 1). To the best of our knowledge, the use of H2NSO3H has not pre-
viously been reported for the preparation of 5-substituted tetrazoles.
Scheme 1
The synthetic protocol was standardized by carrying out the reaction between 4-nitroben-
zonitrile and sodium azide as a model to examine such parameters as effective catalyst
loading, solvent, temperature, and time.
The results are summarized in Table 1.
The optimal temperature was found to be 120 C in DMF to afford the maximum
yield. Further improvements of yields were not observed on increasing the loading of the
o
o
catalyst beyond 0.1 mmol (Table 1, Entry 16). In the absence of the catalyst at 120 C,
no reaction occurred even after 10 h (Table 1, Entry 17). Under the conditions described,
good to excellent yields were obtained in all cases (Table 2) using a variety of aromatic
nitriles.
Under similar conditions, 4-methoxyphenyl- and benzhydrylacetonitriles with
sodium azide gave 82% and 72% yields respectively (Table 2, Entries 8 and 10).
Table 1
Effect of Various Parameters on the Synthesis of p-Nitrophenyltetrazole
Entry
H3NSO3(mmol)
Solvent
Temp.(oC)
Time (hrs)
Yield (%)a
1
2
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.04
0.04
0.06
0.08
0.1
DMF
r.t.
r.t.
10
10
10
10
10
10
10
10
10
10
10
10
10
10
5
0
0
CH2Cl2
CH3OH
CH3CN
DMF
3
r.t.
r.t.
0
4
0
5
80
39
30
5
6
CH2Cl2
CH3OH
CH3CN
DMF
7
62
80
5
8
10
35
40
50
70
85
95
95
95
0
9
80
10
11
12
13
14
15*
16
17
DMF
DMF
100
100
100
100
120
120
120
120
DMF
DMF
0.1
0.1
DMF
DMF
0.2
0
DMF
DMF
5
10
aReaction conditions: 4-nitrobenzonitrile (2 mmol), NaN3 (3 mmol), above solvents (5 mL).

348
Aminimanesh and Shirian

Synthesis of 5-Substituted Tetrazoles
349

350
Aminimanesh and Shirian

Synthesis of 5-Substituted Tetrazoles
351
Table 3
Comparison Between Sulfamic Acid and Some Other Promoters for the Synthesis of 5-(4-
nitrophenyl)-1H-tetrazole from the Reaction of 4-nitrobenzonitrile with Sodium Azide
Entry
Catalyst
Solvent
Temp. (oC) Time (hrs) Yield (%)a
1
2
3
4
5
6
Ln(OTf)3-SiO2
TCT
B(C6H5)3
DMF/MeOH
DMF
DMF
100
120
120
85
7
3
8745
7346
9547
8443
7848
95
6
Amberlyst-15
Natrolite Zeolite
This method (H3NSO3) DMF
DMSO
DMF
12
12
5
120
120
aIsolated yield.
However only very low yields (10–15%) of the desired products were obtained with
aceto- and propane nitriles. Only the monoaddition product was obtained with 1,4-dicya-
nobenzene (Table 2, Entry 5).
The effectiveness of sulfamic acid was compared with some previously reported
methods (Table 3). The results illustrate that sulfamic acid is better than several reported
methods with respect to reaction times and yields.
In conclusion, sulfamic acid is a highly efficient, convenient catalyst for the synthesis
of 5-substituted tetrazoles from the addition of sodium azide to a number of aromatic and
aliphatic nitriles in DMF in good to excellent yields. The easy availability and handling
of the H3NSO3 as a mild solid acid catalyst, avoidance of the direct use of hazardous
hydrazoic acid, shorter reaction times, simple work-up and purification procedures, and
reusability of the catalyst for at least three subsequent cycles are the most significant
advantages over other existing methods.
Experimental Section
Chemicals were purchased from Merck, Fluka, and Aldrich chemical companies. The
solvents were used as provided from company. All yields refer to the isolated products.
The progress of reaction was monitored by TLC. IR and 1H NMR spectra were recorded
using a Shimadzu Infrared Spectrophotometer FT-IR Model IR Prestige 21 (KBr pellets)
1
and a 90 MHz Jeol FT-NMR spectrometer, respectively. H NMR chemical shifts were
measured relative to TMS. Melting points were recorded using a Thermo Scientific 9100
melting point apparatus, and are uncorrected. Safety Note: Since hydrazoic acid may be
generated, all reactions should be performed in an efficient hood.
Typical Procedure for the Synthesis of Tetrazoles. 5-(4-Nitrophenyl) Tetrazole
A mixture of 4-nitrobenzonitrile (0.296 g, 2 mmol), sodium azide (0.195 g, 3 mmol), and
sulfamic acid (0.0097 g, 0.1 mmol) was stirred at 120oC in DMF (5 mL) for the appropriate
time (Table 2) until TLC (4:1 n-hexane:ethyl acetate) indicated no further progress in
the conversion. After completion of the reaction (as monitored by TLC), the reaction mix-
ture was cooled to room temperature, then 20 mL diethyl ether was added to the mixture
and stirred for 10 minutes. The catalyst was separated by simple gravity filtration, washed
with diethyl ether (2 £ 10 mL) and dried at 40oC for 30 min. The recovered catalyst was
used for three additional cycles and gave the tetrazole in 95, 85 and 75% (with

352
Aminimanesh and Shirian
4-nitrobenzonitrile). The filtrate was treated with ethyl acetate (30 mL) and 6 N HCl
(20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc
(20 mL). The combined organic layers were dried over anhydrous sodium sulfate and evap-
orated under reduced pressure to give 5-(4-nitrophenyl) tetrazole (0.363 g), 95% yield.
Recrystallization from aqueous ethanol gave the pure product as a white powder, mp.
215–218ꢀC, lit.43 219–220oC. IR (KBr): 3421, 3023, 2978, 2779, 2439, 1644, 1520, 1340,
1
854 cm¡1. H NMR (90 MHz, DMSO-d6): d 13.47 (bs, 1H), 8.07–7.07 (m, 4H). Anal.
Calcd. for C7H5N5O2: C, 43.98, H, 2.62, N, 36.64. Found: C, 44.16, H, 2.91, N, 37.02.
All products are known in the literature and were characterized by elemental analysis
and by FT-IR, 1H NMR and mps which matched those reported in the literature.41–44
5-Phenyl-1H–tetrazole. m.p. 212–214oC, lit.41 215–216oC. IR (KBr): 3434, 3022–
1
2439, 1608, 1563, 1465, 687 cm¡1. H NMR (90 MHz, DMSO-d6) d (ppm): 11.22 (bs,
1H), 8.89–7.93 (m, 5H). Anal. Calcd. for C7H6N4: C, 57.53, H, 4.14, N, 38.33. Found: C,
57.76, H, 4.28, N, 37.96.
5-(2-Chlorophenyl)-1H-tetrazole. m.p. 177–179oC, lit.41 180–181oC. IR (KBr):
3430, 3130–2603, 1601, 1470, 777 cm¡1. 1H NMR (90 MHz, acetone-d6) d (ppm): 13.88
(bs), 8.02–7.09 (m, 4H). Anal. Calcd. for C7H5N4Cl: C, 46.56, H, 2.79, N, 31.02. Found:
C, 46.82, H, 2.96, N, 31.14. 5-(3-Nitrophenyl)-1H-tetrazole. m.p. 183–185oC, lit.41 188–
1
190oC. IR (KBr): 3300, 3087–2751, 1621, 1524, 1349, 727 cm¡1. H NMR (90 MHz,
acetone-d6) d (ppm): 9.46–7.34 (m). Anal. Calcd. for C7H5N5O2: C, 43.98, H, 2.62, N,
36.64. Found: C, 43.82, H, 2.79, N, 36.93.
5-(4-Chlorophenyl)-1H-tetrazole. m.p. 257–259oC, lit.42 261–263oC. IR (KBr):
1
3446, 3094–2637, 1609, 1486, 867, 743 cm¡1. H NMR (90 MHz, acetone-d6) d (ppm):
8.29–7.57 (m). Anal. Calcd. for C7H5N4Cl: C, 46.56, H, 2.79, N, 31.02. Found: C, 46.33,
H, 2.98, N, 31.24. 4-(1H-Tetrazole-5-yl) benzonitrile. m.p. 188–190oC, lit.42 192oC. IR
(KBr): 3413, 3092–2773, 2232, 1652, 1386, 851 cm¡1. 1H NMR (90 MHz, acetone-d6) d
(ppm): 8.40–7.93 (m). Anal. Calcd. for C8H5N5: C, 56.14, H, 2.94, N, 40.92. Found: C,
56.32, H, 3.17, N, 40.51.
5-(4-Bromophenyl)-1H-tetrazole. m.p. 265–268oC, lit.41 268–270oC. IR (KBr):
1
3434, 3084–2474, 1910, 1602, 1482, 830, 745 cm¡1. H NMR (90 MHz, DMSO-d6) d
(ppm): 8.03–7.77 (m). Anal. Calcd. for C7H5BrN4: C, 37.36, H, 2.24, N, 24.89. Found: C,
37.62, H, 2.45, N, 25.11.
5-(Benzhydryl)-1H-tetrazole. m.p. 143–146oC, lit.44 148–149oC. IR (KBr): 3421,
1
3031–2779, 1668, 1384 cm¡1. H NMR (90 MHz, acetone-d6) d (ppm): 8.00 (bs, 1H),
7.36 (bs, 10H), 5.60(s, 1H). Anal. Calcd. for C14H12N4: C, 71.17, H, 5.12, N, 23.71.
Found: C, 71.48, H, 5.36, N, 23.16.
5-(4-Methoxybenzyl)-1H-tetrazole. m.p. 150–153oC, lit.41 154–156oC. IR (KBr):
3442, 3105–2611, 1612, 1513, 1247, 835 cm¡1. 1H NMR (90 MHz, acetone-d6) d (ppm):
12.50 (bs), 7.29–6.68 (m, 4H), 4.30 (s, 2H), 3.75 (s, 3H). Anal. Calcd. for C9H10ON4: C,
56.83, H, 5.30, N, 29.46. Found: C, 56.51, H, 5.57, N, 29.76. 5-(4-Methoxyphenyl)-1H-
tetrazole. m.p. 225–228oC, lit.44 230–232oC. IR (KBr): 3445, 3077–2360, 1616, 1508,
1
1266, 1182, 834 cm¡1. H NMR (90 MHz, DMSO-d6) d (ppm): 13.48 (bs), 8.07–7.07
(m, 4H), 3.82 (s, 3H). Anal. Calcd. for C8H8ON4: C, 54.54, H, 4.58, N, 31.80. Found: C,
54.31, H, 4.73, N, 32.14.
Acknowledgments
We are grateful to the Department of Chemistry of Payame Noor University and Ministry
of Science Research and Technology for the financial support.

Synthesis of 5-Substituted Tetrazoles
353
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