A practical multigram-scale method for the green synthesis of 5-substituted-1H-tetrazoles in deep eutectic solvent

Article abstract of DOI:10.1016/j.tetlet.2018.12.037

A series of 5-substituted-1H-tetrazoles have been efficiently synthesized in moderate to excellent yields (68–90%) under mild reaction conditions by combining aryl aldehydes, hydroxylamine hydrochloride with sodium azide in the presence of catalytic amoun

Full text of DOI:10.1016/j.tetlet.2018.12.037

Accepted Manuscript
A practical multigram-scale method for the green synthesis of 5-substitu-
ted-1H-tetrazoles in deep eutectic solvent
Xingquan Xiong, Chao Yi, Xu Liao, Shilin Lai
PII:
S0040-4039(18)31479-5
https://doi.org/10.1016/j.tetlet.2018.12.037
TETL 50500
DOI:
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
5 November 2018
14 December 2018
17 December 2018
Please cite this article as: Xiong, X., Yi, C., Liao, X., Lai, S., A practical multigram-scale method for the green
synthesis of 5-substituted-1H-tetrazoles in deep eutectic solvent, Tetrahedron Letters (2018), doi: https://doi.org/
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0.1016/j.tetlet.2018.12.037
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Tetrahedron Letters
A practical multigram-scale method for the green synthesis of 5-substituted-1H-
tetrazoles in deep eutectic solvent
*
Xingquan Xiong , Chao Yi, Xu Liao, Shilin Lai
College of Materials Science and Engineering, University of Huaqiao, Xiamen 361021, China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A series of 5-substituted-1H-tetrazoles have been efficiently synthesized in moderate to
excellent yields (68–90%) under mild reaction conditions by combining aryl aldehydes,
hydroxylamine hydrochloride with sodium azide in the presence of catalytic amount of
2
Cu(OAc) in deep eutectic solvent (DES). The new synthetic method has many advantages, such
Available online
as high conversion, green reaction medium, easy work-up, low cost, and environment friendly.
Keywords:
5
-Substituted-1H-tetrazoles
2009 Elsevier Ltd. All rights reserved.
Aldehydes
One-pot synthesis
Deep eutectic solvent
Green chemistry
O
1
. Introduction
The tetrazole ring is an important five-membered heterocyclic
CH3
HN
HO
O
O
N
O
nucleus that has been widely found in nature such as pyrimidine,
purine, and other natural products [1]. In addition, many synthetic
pharmaceutical drugs and agrochemical products also contain
tetrazole groups. Not surprisingly, therefore, research on efficient
synthesis of tetrazoles has been a hot topic in the field of organic
chemistry, which not only attracted extensive attention from
academic research, but also drew high attention from industrial
field [2].
N
N
N
N
N
N
N
N
N
H
N
N
N
R
N
N
TAK-456
(
Antifungal drug)
(Anti-HIV drug)
Fig. 1. Some examples of biologically active tetrazole-containing compounds.
In general, there are several conventional methods to
synthesize 5-substituted 1H-tetrazoles through reaction of nitriles
The tetrazole-based drugs can interact with many enzymes
and receptors in the organism and they possess different kinds
of biological activities [3]. Several drugs and drug candidates
with tetrazole moiety endowed with promising biological activity
against dreadful diseases, such as hypertension, cancer and HIV
with hydrazoic acid (HN ), trimethylsilyl azide (TMSN ), and
3
3
sodium azide (NaN ), respectively (Scheme 1). Among these
3
methods, the [3+2] cycloaddition reaction between nitriles and
TMSN , or between nitriles and NaN has been an attractive and
[
4-6]. Among them, 5-substituted-1H-tetrazoles have been
3
3
useful method. The reactions were carried out by using catalysts
such as Pd-2A3HP-MCM-41 [8], Pd-SBT@MCM-41 [9], Pd-
isatin-boehmite [10], Pd@polymer [11], Cu/Zn alloy nanopowder
recognized as privileged structural motifs and they have become
increasingly important and useful in drugs due to its broad range
of biological activities (Fig. 1) [7]. All of them have good clinical
therapeutic effect.
[
12], ZrOCl ·8H O [13], zinc oxide [14], Fe(OAc) [15],
2
2
2
NaHSO ·SiO [16], AlCl [17], Zn(OTf) [18], ZnBr [19], β-
4
2
3
2
2
N
CH3
CH3
N
cyclodextrin [20], polymeric copper (II) complex [21],
Fe O @SiO -aminotet-Cu(II) [22], CuO nanoparticles [23], L-
N
HO
O
CH3
N
N
3
4
2
H
N
HN
N
N
N
proline [24], nano-Cu
Cu(OAc)2 [27], Fe O @SiO -TCT-PVA-Cu(II)
Fe O @SiO -dendrimer-encapsulated
2
O–MFR [25], Cu-MCM-41 [26],
O
[28],
urea-
3
4
2
HO
Cu(II)
[29],
CH3
3
4
2
N
O
CH COOH [30], Cu(II)-adenine-MCM-41 [31], Ni (II)-
O
3
N
O
Fe O @tryptophan [32], Fe
3
O4@AMPD@Ni [33] et al. The
3
4
Cl
Losartan
Olmesartan Medoxomil
(Antihypertensive drug)
reported methods suffer from drawbacks such as use of high-
boiling-point organic solvents (such as DMF and DMSO),
(
Antihypertensive drug)
expensive metals (Pd catalyst), harsh reaction conditions
o
(
>200 C), and formation of highly volatile and toxic HN as by
3
product. Therefore, a simple and green approach for the synthesis

2
Tetrahedron
of 5-substituted 1H-tetrazoles is still highly desired and in
47%, respectively. CuCl ·2H O (Table 1, entry 5) also gave low
2 2
demand.
yield of 46%. When we used Cu O (Table 1, entry 6) and
2
Cu(NO ) ·3H O (Table 1, entry 7) as catalysts, the yields were
improved to 70 and 79%, respectively. To our delight, an
3
2
2
R
C
N
OH
N
R
NaN3
Azide source
excellent yield was obtained when Cu(OAc) (20 mol%) was
2
Pd, Cu,
Zn, Al, et al.
Cu(OAc)2
DMF
applied (Table 1, entry 8). However, no further improvement in
H
N
catalysts
R
N
the yield could be achieved, when the amount of Cu(OAc)
increased up to 25 mol% at 100 C (Table 1, entry 9).
2
was
o
N
N
NH2-NHCHO
NaNO2/HCl
NH2OH·HCl
Cu(OAc)2 NaN3
DES
The choice of the solvent also played a crucial role. Very low
yields (<5% and 23%) were obtained in the DES of ChCl-
glycerol, and sorbitol-urea-NH Cl when Cu(OAc) (20 mol%)
O
OEt
4
2
R
H
NH2
X
was applied (Table 1, entries 10 and 11), respectively. Further
research showed that the moderate yields could be obtained by
R
This work
using DMF and CH CN as solvent (66 and 72%, Table 1, entries
3
Scheme 1. Synthetic methods of 5-substituted-1H-tetrazoles.
1
2 and 13). However, when EtOH and H O were used as solvents,
2
With the rise of green chemistry, clean and efficient chemical
reaction has become an inevitable trend of chemical industrial
development. At present, most chemical reactions need to be
carried out in traditional organic solvents, while organic solvents
have obvious disadvantages, such as high toxicity and
very low yields could be obtained and most of the starting
materials could be recovered (Table 1, entry 14 and 15).
Therefore, the Cu(OAc) -ChCl-urea catalytic system,
2
integrating the advantages of Cu(OAc) and DES, show great
2
volatilization.
Thus,
emission of volatile organic solvents
potential for synthesizing 5-substituted 1H-tetrazole derivatives.
is one of the major contributors to chemical pollution and it is
urgent to find environmentally friendly media and solvents.
DESs are eutectic mixtures of quaternary ammonium salts and
hydrogen bond donors with melting points low enough [34].
DESs are known to be a good alternative to traditional solvents
and ionic liquid (ILs) [35, 36]. In recent years, much attention has
recently been paid to their applications in organic synthesis as
green solvents with many successful results because the
components of the DESs are widely available in nature,
inexpensive, non-toxic, and biodegradable [37-45].
It was concluded that the optimal conditions for the synthesis of
5
-substituted 1H-tetrazoles was Cu(OAc)2 dosage of 20
o
mol%, reaction temperature of 100 C in ChCl-urea, and reaction
time for 12 hours.
Table 1 Effect of different catalysts, solvents and temperature on the
a
synthesis of 5-phenyl 1H-tetrazole.
H
O
catalyst
solvent,
N
N
N
NH2OH·HCl NaN3
N
o
b
Entry Catalyst (mol%)
Solvent
Temp ( C)
Yield (%)
1
2
3
4
None
ChCl-urea
ChCl-urea
ChCl-urea
ChCl-urea
100
100
100
100
0
In the field of 5-substituted 1H-tetrazoles synthesis, nitrile
compounds have been widely used as starting materials.
However, most nitriles are toxic and difficult to biodegrade.
Compared with nitriles, aldehydes are more available, cheaper,
and less toxic. In addition, in order to avoid using high-boiling-
point organic solvents and harsh reaction conditions in the
reaction process, herein we report for the first time a simple,
convenient, and green protocol for the synthesis of 5-substituted
FeCl
3
(20%)
<5
38
47
2
Zn(OAc) (20%)
ZnCl (20%)
2
CuCl
20%)
O (20%)
Cu(NO ·3H
20%)
Cu(OAc) (20%)
2 2
·2H O
5
6
7
ChCl-urea
ChCl-urea
ChCl-urea
100
100
100
46
70
79
(
2
Cu
3
)
2
2
O
(
8
9
2
ChCl-urea
ChCl-urea
ChCl-glycerol
Sorbitol-urea-
100
100
100
90
90
<5
1
H-tetrazoles by reaction of aldehydes, NH OH·HCl and NaN in
Cu(OAc)
Cu(OAc)
2
(25%)
(20%)
2
3
1
0
2
the presence of 20 mol % of Cu(OAc) as catalyst in DES of
2
choline chloride (ChCl)-urea (Scheme 2).
11
Cu(OAc)
2
(20%)
100
23
4
NH Cl
H
12
13
14
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
2
(20%)
(20%)
(20%)
(20%)
DMF
100
75
75
66
72
<5
<5
O
N
Cu(OAc)2
R
CH
3
CN
NH OH·HCl NaN3
N
N
2
o
EtOH
R
H
DES, 100 C
N
1
5
H
2
O
100
a
Scheme 2. One-pot synthesis of 5-substituted 1H-tetrazoles in DES.
Reaction conditions: benzaldehyde (2.0 mmol), NH
NaN (2.4 mmol), DES (2.0 mL), catalyst (20 mol%) at 100 C for 12 h;
Isolated yield.
2
OH·HCl (2.0 mmol),
o
b
3
2
. Results and discussion
Prompted by the aforementioned excellent result of
The main aim of this study was to optimize the conditions of
-substituted 1H-tetrazoles synthesis. Therefore, the catalytic
Cu(OAc) -ChCl-urea catalytic system, we further investigate the
2
5
practicality of the catalytic system. Using the optimized reaction
condition, the one-pot conversion was further expanded to a
broader range of various aryl/alkyl aldehydes in order to evaluate
the scope and limitations of the method. The obtained results are
summarized in Table 2. We were pleased to find that various aryl
aldehydes with electron-withdrawing groups as well as electron-
donating groups reacted smoothly with NH OH·HCl and NaN to
performance was investigated in one-pot three-component
synthesis of 5-phenyl 1H-tetrazole as a model product under
several reaction conditions, such as amount of the catalyst,
temperature, and solvent nature. The obtained results were shown
in Table 1.
All reactions reacted at 100°C or 75°C for 12 h in different
solvents, such as DES, DMF, CH CN, EtOH, and H O. Initially,
2
3
3
2
give the desired 5-substituted 1H-tetrazoles in moderate to
excellent yields (68-90%, Table 2, entries 1-9). The results
obviously indicated the generality and scope of the reaction with
respect to various aryl aldehydes. Unfortunately, when propionic
acid was used as the starting material, the reaction could not be
carried out normally (Table 2, entry 10).
the mixture of benzaldehyde and NH OH·HCl was reacted with
2
NaN in the DES mixture of ChCl and urea without the addition
3
of metal catalyst (Table 1, entry 1). However, no desired product
was observed. When FeCl was added into the system as catalyst,
3
the corresponding product 5-phenyl 1H-tetrazole was obtained
with very low yield (<5%, table 1, entry 2). Zn(OAc) (Table 1,
2
entry 3) and ZnCl (Table 1, entry 4) gave low yields of 38 and
2

Table 2 Synthesis of 5-substituted 1H-tetrazoles under the optimized
reaction condition.
attack of the nitrogen atom of hydroxylamine to the active
carbonyl group, and then benzaldehyde oxime is obtained. Then,
a
O
HN N
Cu(OAc)2
Cu(OAc) readily activated C=N bond by cocoordinating with
2
NH OH·HCl
NaN3
2
N
o
oxygen atom of benzaldehyde oxime. This might facilitate the
R
H
DES, 100 C
R
N
[
3+2] cycloaddition between azide ion and the C=N bond of
benzaldehyde oxime, and finally H O elimination gives the
corresponding 5-phenyl-1H-tetrazole product.
2
Yield
o
Lit m.p.
( C)
Entry
1
Substrate
Product
m.p. ( C)
o
(%)
H
N
O
CH3
215-216
N
N
H3C
NH2
NH2
90
68
215-216
CH3
O
C
[
19]
3
H C
N
Cu(II)
N
OH
Cl
H3C
H3C
N
Cl
H
O
N
N
N
HO
Cl
Cl
264-266
[19]
2
3
4
264-265
236-237
230-231
NH2
NH2
O
H2
N
O
C
C
NH2
N
Cu(II)
OH
NH2
Cu(II)
Cu(II)
C
O
H
O
N
H
N
N
N
H2
HO
HO
234-235
[19]
O
N
N
N
85
74
O
H
N
H
N
-H2O
H
N
+
NH2OH·HCl
H
H
O
N
N
CH3O
CH O
231-232
[46]
Na
N N N
3
N
N
N
N
N
-
H2O
N
O
H
H
N
HO
-Cu(II)
N
N
2
15-217
[46]
HO
CH3O
5
81
215-216
CH3O
N
Scheme 3. Plausible mechanism for the synthesis of 5-phenyl-1H-tetrazole
catalyzed by Cu(OAc)
in DES of ChCl-urea.
2
H
O
N
N
O2N
O N
218-219
[19]
6
7
2
N
70
89
217-219
223-225
N
3
. Conclusions
In summary, we have reported herein a highly efficient and
green method for the multi-gram scale synthesis of 5-substituted
H-tetrazoles without isolation of the intermediate through the
H
N
O
N
2
20-222
[47]
N
N
OH
OH
1
H
N
204-205 one-pot cascade reaction from aryl aldehydes by using Cu(OAc)2
8
9
N
N
86
88
203-204
210-212
--
CHO
CHO
O
O
[47]
as catalyst in DES of ChCl-urea for the first time. In all cases,
the desired 5-substituted 1H-tetrazoles were isolated in moderate
to excellent yields. This newly developed method avoids the
usage of toxic chemicals/high-boiling-point organic solvents, or
N
H
N
211
[19]
N
N
N
N
N
H
N
N
b
avoids formation of highly volatile and toxic HN by-product as
3
1
0
CH
3
CH
2
CHO
NR
--
N
previously reported. We believe that our strategy could be
broadly applicable for the facile and high-yield production of
other novel 5-substituted 1H-tetrazoles with great promise for
various applications.
N
a
Reaction conditions: aldehyde (2.0 mmol), NH
2 3
OH·HCl (2.0 mmol), NaN
o
b
(
2.4 mmol), DES (2.0 ml), catalyst (20 mol%) at 100 C for 12 h; NR=No
reaction.
Finally, the multi-gram scale synthesis of the 5-substituted
H-tetrazoles was investigated in the case of 5-phenyl-1H-
1
4
. Experimental section
tetrazole as a model reaction. The detailed results were
summarized in Table 3. Encouraged by the above results, we
increased the scale of the reaction to 5.0, 25.0, 50.0, 100.0 mmol,
respectively, keeping the reaction stoichiometry unchanged. The
reactions were found to proceed smoothly and the corresponding
product was obtained in good to excellent yields.
4
.1 Materials and instrumentation
All chemicals were purchased from Aladdin Reagent
Company. The progress of the reactions was monitored by thin
layer chromatography (TLC) using silica gel plates.
-
1
The IR spectra were obtained using a FT-IR (4000~400 cm )
Table 3 Scale-up synthesis of 5-phenyl 1H-tetrazole.
-1
spectrometer (Nicolet Nexus FT-IR spectrometer, USA) at 4 cm
resolution and 32 scans. Samples were prepared using the KBr
disc method. NMR spectra were acquired in CDCl on a Bruker
DMX-400 spectrometer at 400 MHz for H NMR, the chemical
H
O
N
Cu(OAc)2
N
N
NH OH·HCl
NaN3
2
o
DES, 100 C
3
N
1
Scale
mmol)
Isolated yield
(%)
Isolated Product
(g)
Entry
Time (h)
shifts are given in δ values from TMS as an internal standard.
(
4
.2 Typical procedure for the preparation of DES
1
2
3
4
5.0
12
15
20
28
91
85
90
88
0.66
3.14
The DESs were synthesized according to the reported
25.0
procedures in the literatures [48-50]. ChCl (100 mmol) and urea
200 mmol) were mixed in a round-bottomed flask in the ratio of
50.0
6.58
(
o
100.0
12.88
1:2, then the solid mixture was heated and maintained at 80 C
with stirring until formation of a colorless homogeneous liquid
with 100% atom economy. The ChCl-urea was allowed to cool to
room temperature, which was used directly for the synthesis of 5-
substituted 1H-tetrazoles without any further purification.
We propose a mechanism of the Cu(OAc) catalyzed C-N
2
coupling reaction for the synthesis of 5-substituted 1H-tetrazoles
as shown in Scheme 3. After the activation of the carbonyl group
of benzaldehyde catalyzed by Cu(OAc) and the nucleophilic
2

4
Tetrahedron
4
.3 Typical procedure for the synthesis of 5-substituted 1H-
10.92 (s, 1H), 7.99 (d, J=7.7 Hz, 1H), 7.42 (t, J=7.7 Hz, 1H),
tetrazoles
7.13–6.97 (m, 2H), 3.36 (s, 1H).
In a typical reaction, a mixture of aldehyde (2.0 mmol),
5-(Furan-2-yl)-1H-tetrazole (Table 2, entry 8): m.p. 203-
o
-1
hydroxylamine hydrochloride (2.0 mmol), NaN (2.4 mmol) and
204 C; FT-IR (KBr disc) cm : 3115, 2930, 2362, 1641, 1527,
3
1
DES (2.0 mL) in a round-bottomed flask were added Cu(OAc)
20 mol%). Then the reaction mixture was heated to 100 C in an
1388, 1240, 1020, 890, 758; H NMR (400 MHz, CDCl ) δ: 7.68
2
3
o
(
(d, J=1.1 Hz, 1H), 7.36 (d, J=3.6 Hz, 1H), 6.68 (dd, J=3.5, 1.8
oil bath for 12 hours. After completion of reaction, as detected by
TLC, the mixture was cooled to room temperature then treated
with 5 N HCl (5 mL) and extracted with EtOAc (3×10 mL). The
organic phase was concentrated and washed with 1 N HCl,
saturated aqueous sodium chloride, then dried over anhydrous
Na SO and concentrated under vacuum by rotary evaporator.
Hz, 1H).
2
-(1H-Tetrazol-5-yl)pyridine (Table 2, entry 9): m.p. 210-
-1
o
2
1
12 C; FT-IR (KBr disc) cm : 3093, 2920, 1600, 1560, 1483,
1
450, 1288, 1160, 1018; HNMR (400 MHz, DMSO-d ) δ: 8.81
6
(d, J=4.2 Hz, 1H), 8.24 (d, J=5.7 Hz, 1H), 8.12 (dt, J=15.4, 7.6
2
4
Hz, 1H), 7.67–7.59 (m, 1H), 3.33 (s, 1H).
The crude products were purified by column chromatography to
give the desired 5-substituted 1H-tetrazoles.
Acknowledgments
4
.4 Multi-gram scale synthesis of 5-phenyl 1H-tetrazole
This work was financially supported by the National Natural
Science Foundation of China (21004024), the Natural Science
Foundation of Fujian Province (2016J01063), the Program for
New Century Excellent Talents in University of Fujian Province
(2012FJ-NCET-ZR03) and the Promotion Program for Young and
Middle-aged Teacher in Science and Technology Research of
Huaqiao University (ZQN-YX103).
To a 150 mL round-bottomed flask equipped with a magnetic
stirrer was added benzaldehyde (10.6 g, 0.1 mol), hydroxylamine
hydrochloride (4.2 g, 0.1 mol), NaN (0.5 g, 0.11 mol), Cu(OAc)
3
2
(
20 mol%) and DES (30 mL). Then the reaction mixture was
o
heated to 100 C for 28 h with vigorous stirring. After completion
of reaction, as detected by TLC, the mixture was cooled to room
temperature, adjusted pH to 1.0 with concentrated HCl, and
extracted with EtOAc (3×50 mL). The organic phase was
concentrated and washed with 1 N HCl, saturated aqueous
sodium chloride, then dried over anhydrous MgSO4 and
concentrated under vacuum by rotary evaporator. The crude
product was purified by column chromatography to give 5-
phenyl 1H tetrazole as a white solid (12.9 g, 88% yield).
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.5 Spectroscopic data of 5-substituted 1H-tetrazoles
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2
H).
o
4
-(1H-Tetrazol-5-yl)phenol (Table 2, entry 3): m.p. 236-237 C;
-
1
FT-IR (KBr disc) cm : 3103, 2933, 2847, 2746, 2634, 1612,
505, 1408, 1294, 1180; HNMR (400 MHz, DMSO-d ) δ: 10.15
1
1
(
1
6
9
.
M. Nikoorazm, A. Ghorbani-Choghamarani, M. Ghobadi, S. Massahi,
Appl. Organometal. Chem. 31 (2017) e3848.
s, 1H), 7.87 (d, J=8.5 Hz, 2H), 6.96 (d, J=8.5 Hz, 2H), 3.33 (s,
H).
1
0. A. Jabbari, B. Tahmasbi, M. Nikoorazm, A. Ghorbani-Choghamarani,
Appl. Organometal. Chem. 32 (2018) e4295.
5
-(4-Methoxyphenyl)-1H-tetrazole (Table 2, entry 4): m.p.
o
-1
11. Y. He, C. Cai, Catal. Lett. 140 (2010) 153.
2. G. Aridoss, K. K. Laali, Eur. J. Org. Chem. 31 (2011) 6343.
2
1
(
30-231 C; FT-IR (KBr disc) cm : 3058, 2985, 2914, 1604, 1561,
481, 1380, 1342, 1282; HNMR (400 MHz, DMSO-d ) δ: 7.98
1
1
6
13. M. R. M. B. Gowd, M. A. Pasha, J. Chem. Sci. 123 (2011) 75.
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d, J=8.3 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 3.85 (s, 3H), 3.32 (s,
H).
1
1
5. J. Bonnamour, C. Bolm, Chem. Eur. J. 15 (2009) 4543.
3
-Methoxy-4-(1H-tetrazol-5-yl)phenol (Table 2, entry 5): m.p.
16. B. Das, C. R. Reddy, D. N. Kumar, M. Krishnaiah and R. Narender,
Synlett. 3 (2010) 391.
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o
-1
2
1
7
1
15-216 C; FT-IR (KBr disc) cm : 3446, 3109, 2914, 1604, 1525,
380, 1340, 1288; HNMR (400 MHz, DMSO-d ) δ: 9.76 (s, 1H),
.66–7.52 (m, 1H), 7.50 (d, J=8.2 Hz, 1H), 6.96 (d, J=8.2 Hz,
H), 3.87 (s, 3H), 3.32 (s, 1H).
1
6
2
135.
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19. Z. P. Demko, K. B. Sharpless, J. Org. Chem. 66 (2001) 7945.
1
2
0. R. Dipak, Y.B. Patil, P. G. Wagh, K. Ingole, D. S. Singh, New J.
Chem. 37 (2013) 3261.
5
-(4-Nitrophenyl)-1H-tetrazole (Table 2, entry 6): m.p. 217-
-1
o
2
1
2
19 C; FT-IR (KBr disc) cm : 3446, 3109, 2914, 1604, 1525,
340, 1288, 860; H NMR (400 MHz, CDCl ) δ: 8.45–8.37 (m,
H), 8.32 (dd, J=24.3, 9.0 Hz, 2H).
21. S. Layek, R. Ganguly, D. D. Pathak, J. Organometal. Chem. 870
(2018) 16.
1
3
2
2. M. Nasrollahzadeh, M. Sajjadi, H. A. Khonakdar, J. Mol. Struc. 116
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25. S. Behrouz, J. Saudi Chem. Soc. 21 (2017) 220.
(
o
2
-(1H-Tetrazol-5-yl)phenol (Table 2, entry 7): m.p. 223-225 C;
-
1
2
FT-IR (KBr disc) cm : 3254, 3057, 2939, 1604, 1545, 1475,
361, 1292, 1071, 813, 744; H NMR (400 MHz, DMSO-d ) δ:
1
1
6

2
2
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3
6 (2016) 480.

6
Tetrahedron
Highlights
•
Practical one-pot reaction for preparation of 5-
substituted-1H-tetrazoles.
•
Without using high boiling point or volatile
organic solvents in the reaction.
•
Easy reaction set-up and multigram scale.