Sulfated tungstate a heterogeneous acid catalyst for synthesis of 4-aryl-NH-1,2,3-triazoles by 1,3-dipolar cycloaddition of nitroolefins with NaN3

Article abstract of DOI:10.1080/00397911.2019.1612919

A facile and new method for the synthesis of 4-aryl-NH-1,2,3-triazoles from nitroolefins and NaN₃ by 1,3-dipolar cycloaddition reaction, employing a mild solid inorganic acid sulfated tungstate as a heterogeneous catalyst, has been developed. T

Full text of DOI:10.1080/00397911.2019.1612919

Synthetic Communications
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Sulfated tungstate a heterogeneous acid catalyst
for synthesis of 4-aryl-NH-1,2,3-triazoles by 1,3-
dipolar cycloaddition of nitroolefins with NaN3
Snehalata B. Autade & Krishnacharya G. Akamanchi
To cite this article: Snehalata B. Autade & Krishnacharya G. Akamanchi (2019): Sulfated
tungstate a heterogeneous acid catalyst for synthesis of 4-aryl-NH-1,2,3-triazoles by
1,3-dipolar cycloaddition of nitroolefins with NaN3, Synthetic Communications, DOI:
10.1080/00397911.2019.1612919
To link to this article: https://doi.org/10.1080/00397911.2019.1612919
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https://doi.org/10.1080/00397911.2019.1612919
Sulfated tungstate a heterogeneous acid catalyst for
synthesis of 4-aryl-NH-1,2,3-triazoles by 1,3-dipolar
cycloaddition of nitroolefins with NaN3
Snehalata B. Autade and Krishnacharya G. Akamanchi
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai,
MH, India
ABSTRACT
ARTICLE HISTORY
Received 6 January 2019
A facile and new method for the synthesis of 4-aryl-NH-1,2,3-triazoles
from nitroolefins and NaN3 by 1,3-dipolar cycloaddition reaction,
employing a mild solid inorganic acid sulfated tungstate as a hetero-
geneous catalyst, has been developed. The protocol emphasizes
broad substrate scope with many functionalities, less reaction time,
stability to open air, easy work-up, and with good to excellent yields.
KEYWORDS
1,3-Dipolar cycloaddition;
heterogeneous catalysis;
nitrostyrenes; sulfated
tungstate; 1,2,3-triazoles
GRAPHICAL ABSTRACT
Introduction
Five member nitrogen heterocyclic motifs are ubiquitous in useful organic compounds.
Amongst them, 1,2,3-triazoles are an important class that finds widespread applications
in the areas such as medicinal chemistry,[1–6] agrochemistry, material chemistry, dyes,
corrosion inhibitors, and photo stabilizers.[1,7–9] For example, 1,2,3-triazoles show a
broad spectrum of biological activities,[10] including antibacterial, herbicidal, fungicidal,
antiallergic, and anti-HIV. Specifically, 4-aryl-1H-1,2,3-triazoles were found as human
methionine aminopeptidase (hMetAP2) and indoleamine 2,3-dioxygenase (IDO) inhibi-
tors, and are expected to become medicines to treat cancers, AIDS, Alzheimer’s disease,
tristimania, cataracts, and some other serious diseases.[11,12] The growing importance of
1,2,3-triazoles is highlighted with some examples such as 4-(2-chlorophenyl)-1H-1,2,3-
triazole are indoleamine 2,3-dioxygenase (IDO) inhibitors; azahistidine, an unnatural
amino acid; ML295, which is a monoacylglycerol lipase ABHD6 selective inhibitor; and
4-(3,4-dibromophenyl)-1H-1,2,3-triazole a hMetAP2 inhibitor (Fig. 1).[11]
CONTACT Krishnacharya G. Akamanchi
kgap@rediffmail.com
Department of Pharmaceutical Sciences and
Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
Supplemental data for this article can be accessed on the publisher’s website.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
ß 2019 Taylor & Francis Group, LLC

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S. B. AUTADE AND K. G. AKAMANCHI
Figure 1. Representative biologically active 1,2,3-triazoles.
An extensive range of chemosensors contains click-derived 1,2,3-triazoles where the
triazole motif plays a functional role.[9] Few other examples of 1,2,3-triazole derivatives
are (1-benzyl-1H-1,2,3-triazole-4-yl)methanol (BTM) and (1-(pyridin-4-yl methyl)-1H-
1,2,3- triazole-4-yl)methanol (PTM) are corrosion inhibitor for steel.[13]
Development of methods for the synthesis of 1,2,3-triazoles has gained much
attention.[14–17] There are numerous methods for synthesis of 1,2,3-triazoles, like
organo-catalyzed azide-ketone cycloaddition,[18–21] I2/TBPB oxidative cyclization of
N-tosylhydrazones and anilines,[15] the multi-component reaction involving aldehydes,
nitroalkanes, and organic azides,[22,23] cyclization reactions of a,a-dichlorohydrazones
and primary amines,[24,25] the copper-catalyzed cyclization of hydrazones and azides[26]
using a catalyst, such as palladium in an inert atmosphere[27] or p-TsOH.[28] The pio-
neering work on synthesis of 1,2,3-triazole by 1,3-dipolar cycloaddition dates back to
1960s when Huisgen and coworkers disclosed route to make 1,2,3-triazole moiety
through thermal induced dipolar cycloaddition between alkynes and azides.[29–31]
Alkyne-azide 1,3-dipolar cycloaddition reactions catalyzed by Cu[32–35] and Ru[36–39] are
the most commonly utilized methods for the synthesis of N-substituted 1,2,3-triazoles
and commonly referred as click chemistry. Ir-catalyzed azide-alkyne cycloaddition
(IrAAC),[40,41] are the other approaches. In the triazole synthesis, some multicomponent
reactions to construct triazoles from terminal alkynes are reported.[42–46] However, there
are few papers discovering the synthesis of 1,2,3-triazoles from aldehydes[22,47,48], which
involves use of various catalysts such as proline,[48] morpholine,[22] Julia reagent,[47]
NaHSO3/Na2SO3,[49] AlCl3,[50] Al-MCM-41 and sulfated zirconia using a microwave.[51]
Cycloaddition of a,b-disubsituted nitroolefins and sodium azide[2,52] using PTSA,[53]
Amberlyst-15[54] microwave,[55] sulfamic acid,[56] and Bi2WO6 nanoparticles,[57] carbon
based biocatalyst[58]
.
In spite of these several methods, there is scope for new methods especially consider-
ing the use of expensive metals like Rh, Ir, Pd as a catalyst, need of inert atmosphere,
and use of hazardous reagents. Combination of Bronsted acid and NaN3 forms hydra-
zoic acid which is toxic in nature and also susceptible to explosion. Hence, triazole syn-
thesis is mainly conducted under neutral or basic conditions.[59] But, under these

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conditions, competitive cyclotrimerization of arylnitroolefins was observed giving 1,3,5-
triarylbenzenes as undesired byproducts.[52] in the recent attempt by Xue-Jing Quan, to
use acid catalyzed condition resulted in inhibition of the undesired cyclotrimerization
but the acid is used under homogeneous condition,[28] use of acid in homogeneous for-
mat has its own disadvantages. Also other acid catalyzed conversions suffers from limi-
tations such as the use of microwave conditions, high temperature, and requirement of
high catalyst loading. Therefore, there is a need to develop a practically simple heteroge-
neous mild acid catalyzed method for synthesis of 1,2,3-triazoles.
Recently our research group has introduced sulfated tungstate as a heterogeneous
green catalyst and successfully shown its applications in many useful transformations.
Sulfated tungstate is mildly acidic, non-corrosive, reusable, easy to prepare and has
established its effectiveness in amidation, Ritter, Biginelli, Kindler, Strecker,
Willgerodt–Kindler reactions, N-formylation, transamidation, N-monoalkylation of pri-
mary amines, etherification, synthesis of amidine, and 1,3,5-triarylbenzenes.[60] In this
paper, we describe a new application of sulfated tungstate in 1,3-dipolar cycloaddition
of nitroolefins with NaN3.
Result and discussion
Sulfated tungstate was prepared by the well-established procedure in our laboratory and
is described in our earlier publication.[61,62] Preliminary investigations were conducted
using 1:1.2 mole ratio of (E)-(2-nitrovinyl) benzene (1a) and sodium azide as building
blocks in the presence of 25 wt% of a sulfated tungstate and DMF as a solvent at 100 ꢀC
and the expected product 3a was obtained in 95% yield. Encouraged with this result
experiments were conducted to optimize various parameters. To fix the reaction tem-
perature reactions were conducted at different temperatures of 70, 60 and 50 ꢀC. The
reaction proceeded efficiently to afford the target 3a in 95% at 60 ꢀC (Table 1, entry 3).
To screen the suitability of different solvents reactions were performed in polar solvents
like DMSO, ACN and nonpolar solvents like toluene and xylene (Table 1, entries 5–8).
All the solvents were viable for the reaction but the reaction rates were slow as indi-
cated by the lower yields for the same reaction time of 1 h. The reaction in DMSO was
found to be equally good as a solvent but the reaction was bit slower giving 80% in 3 h
(Table 1, entry 6). Towards optimization of catalyst loading reactions were conducted
using different wt% of catalyst such as 30, 15, 10 and 5 wt%.
There was no significant improvement in yield even after increasing the catalyst load-
ing to 30 wt% (Table 1, entry 9). With, a decrease in the catalyst loading up to 10 wt%
the reaction rate and yield remained the same (Table 1, entry 11). With further decrease
to 5% reaction slowed down giving 72% yield in 2 h (Table 1, entry 12). Therefore
10 wt% of catalyst loading with the reaction time of 1 h was considered to be adequate.
With these optimized conditions in hand, we turned our focus to study the substrate
scope of the new method. Changing the electronic nature of the substituents on nitro-
styrene has almost no effect on the overall course of the reaction.
This may be attributed to the high efficiency of this protocol. Nitrostyrenes contain-
ing electron-donating groups (OCH3) works well to offers the respective product with
good yield (Table 2. Entries 8, 9). Electron-withdrawing groups such as NO2 and –CN

4
S. B. AUTADE AND K. G. AKAMANCHI
Table 1. Optimization of reaction conditionsa.
Entry
Solvent
Sulfated Tungstate (wt%)
Temp. (ꢀC)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
DMF
DMF
DMF
DMF
25
25
25
25
25
25
25
25
30
15
10
5
100
70
60
1
1
1
2
3
3
2
2
1
1
1
2
12
95
94
95
81
10
80
46
43
94
94
95
72
0
50
ACN
Reflux
100
100
100
60
60
60
DMSO
Toluene
Xylene
DMF
DMF
DMF
9
10
11
12
13
DMF
DMF
60
60
0
aReaction conditions: 1a (1 mmol), 2 (1.2 mmol), sulfated tungstate, solvent and temperature; bisolated yield of 3a.
Table 2. Substrate scope.
Entry
R
Product
Yield (%)b
1
2
3
4
R1 ¼ H, R2 ¼ H
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
95
88
92
90
91
89
81
82
79
81
76
89
83
84
R1 ¼ 4-Br, R2 ¼ H
R1 ¼ 4-Cl, R2 ¼ H
R1 ¼ 4-F, R2 ¼ H
5
R1 ¼ 2-Cl, 4-Cl, R2 ¼ H
R1 ¼ 4-NO2, R2 ¼ H
R1 ¼ 4-CN, R2 ¼ H
6c
7d
8
R1 ¼ 4-OCH3, R2 ¼ H
R1 ¼ 3-OCH3, 4-OCH3, R2¼ H
R1 ¼ 4-OCH3, R2 ¼ CH3
R1 ¼ H, R2 ¼ ꢁCH2CH3
2-CH3 furan, R2 ¼ H
2-thiophene, R2 ¼ H
2-naphthalene, R2 ¼ H
9
10
11
12
13
14
aReaction conditions: 1 (1 mmol), sodium azide (1.2 mmol), DMF, time; bisolated yield; ctime required 2 h; dtime
required 1.5 h.
reacted with equal ease (Table 2, entries 6–7). Different halogens such as fluoro, chloro
and bromo substituted nitrostyrenes were well tolerated in the transformation (Table 2,
entry 1–4). The method was also found to be suitable for the synthesis of sterically chal-
lenging o-substituted nitrostyrenes providing good yield under the optimized reaction
conditions (Table 2, entry 5).

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Stearic factors were also introduced a- to nitro group as in case of substrates (E)-1-
methoxy-4-(2-nitroprop-1-en-1-yl)benzene and (E)-(2-nitrobut-1-en-1-yl)benzene, both
the substrates reacted smoothly under the optimized reaction conditions to give prod-
ucts in 81% and 76% yield respectively indicating the tolerance of stearic factors and
showing wider substrate scope (Table 2, entries 10 and 11).
In addition, reaction with acid labile heterocyclic nitrostyrene such as (E)-2-(2-nitro-
vinyl) furan and (E)-2-(2-nitrovinyl) thiophene also proceeded smoothly to give
products in 89 and 83% yields, respectively (Table 2, entries 12 and 13). With substrate
(E)-2-(2-nitrovinyl) naphthalene having fused ring system, the reaction was facile giving
84% yield (Table 2, entry 14).
To explore the applicability of the method on a preparative scale, with
substrate (E)-(2-nitrovinyl) benzene, the reaction was successfully scaled up to 1.49 g,
getting the yield of without any significant decrease in the efficiency (92% as
against 95% in 10 mmol scale). The gram-scale reaction was performed in the usual
laboratory setup with a two-neck round-bottomed flask fitted with a reflux conden-
ser. This example clearly establishes the practical feature of this newly devel-
oped method.
To understand the reaction mechanism following studies were carried out.
Tungsten trioxide (WO3), a material close to sulfated tungstate but lacking acidity
was screened. However, no reaction was observed at 60 ꢀC even after 12 h in DMF
as a solvent. This result indicates that sulfated tungstate plays a catalytic role and
not just acts as a solid surface. In the next experiment, the catalyst was suspended
in nitrostyrene and DMF mixture and stirred for 15 min at 60 ꢀC. Then hot filtered,
washed with chloroform, and dried in an oven and recorded FT-IR. The IR spec-
trum showed peaks corresponding to nitrostyrene (1333 cmꢁ1 and 1516 cmꢁ1), indi-
cating its adsorption on the catalyst. Similarly, in another experiment, the catalyst
was suspended in a mixture of sodium azide and DMF, stirred for 15 min at 60 ꢀC
filtered. Hot filtered wash with water and chloroform dried in an oven and recorded
FT-IR. In the IR spectrum, there were no peaks corresponding to azide and only
peaks attributed to the catalyst were observed. Indicating that, sodium azide was not
adsorbed on the catalyst.
Based on these experimental results a mechanism is postulated for the reaction
involving activation of nitrostyrene through H-bonding as well as activation of double
bond and formation of transition state A as depicted in Figure 2 followed by [3 þ 2]
cycloaddition and aromatization driven elimination of NO2 group leading to the forma-
tion of triazole 2a.
In conclusion, the present work described a new protocol for the synthesis of 1,2,3-
triazoles through 1,3 dipolar cycloaddition in presence of sulfated tungstate, a mild and
easy to synthesize, the heterogeneous acid catalyst has been developed. The method is
operationally simple and can be performed under aerobic conditions in the usual
laboratory setup. Mild reaction conditions and tolerance of a wide variety of functional
groups and potential for use in preparative scale are some noteworthy features of this
newly developed method.

6
S. B. AUTADE AND K. G. AKAMANCHI
Figure 2. Postulated mechanism.
Experimental
Procedure for synthesis of 4-phenyl-1H-1,2,3-triazole (2a)
To a stirred solution of nitrostyrene 1 (1 mmol) and sulfated tungstate (10 wt%) in
DMF (2 mL), NaN3 (1.2 mmol) was added and the mixture was stirred at 60 ꢀC for 1 h.
Progress of the reaction was monitored by TLC. After completion of the reaction, the
reaction mixture was cooled down to rt. Then the mixture was diluted by adding ethyl
acetate (10 ml) with stirring. Filtered off the catalyst. The filtrate was washed with
10 mL of water, the organic layer was dried over Na2SO4 and concentrated under
reduced pressure. The crude product was purified by column chromatography on silica
gel (100–200 mesh) and petroleum ether/EtOAc mixture as an eluent to afford pure
product 4-phenyl-NH-1,2,3-triazole with 95% yield.
1
White solid, mp ¼150–151 ꢀC. H NMR (400 MHz, DMSO-d6) d 8.07 (s, 1 H), 7.86
(d, J ¼ 7.5 Hz, 2 H), 7.49 (t, J ¼ 7.5 Hz, 2 H), 7.43 (d, J ¼ 7.3 Hz, 1 H), 7.29 (s, 1 H). 13C
NMR (101 MHz, DMSO-d6) d 167.77 (s), 133.30 (s), 131.19 (s), 129.71 (s), 129.37 (s),
129.01 (s), 126.01 (s).
1
General procedure, H and 13C NMR of compounds are provided in the supplemen-
tary information.
Funding
The authors thank the University Grant Commission, Delhi of India for financial support.

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