CTAB promoted CuI catalyzed green and economical synthesis of 1,4-disubstituted-1,2,3-triazoles

Article abstract of DOI:10.1080/00397911.2018.1439176

A practical, straightforward, and highly efficient CuI mediated green protocol for the regioselective synthesis of 1,4-disubstituted-1,2,3-triazole was developed using cetyltrimethylammonium bromide as a cheap additive in good to excellent yields. Low cat

Full text of DOI:10.1080/00397911.2018.1439176

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CTAB promoted CuI catalyzed green and
economical synthesis of 1,4-disubstituted-1,2,3-
triazoles
Abdul Aziz Ali, Rahul Sharma, Prakash J. Saikia & Diganta Sarma
To cite this article: Abdul Aziz Ali, Rahul Sharma, Prakash J. Saikia & Diganta Sarma (2018):
CTAB promoted CuI catalyzed green and economical synthesis of 1,4-disubstituted-1,2,3-triazoles,
Synthetic Communications, DOI: 10.1080/00397911.2018.1439176
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SYNTHETIC COMMUNICATIONS®
https://doi.org/10.1080/00397911.2018.1439176
CTAB promoted CuI catalyzed green and economical synthesis
of 1,4-disubstituted-1,2,3-triazoles
a
a
b
a
Abdul Aziz Ali , Rahul Sharma , Prakash J. Saikia , and Diganta Sarma
a
b
Department of Chemistry, Dibrugarh University, Dibrugarh, Assam, India; Analytical Chemistry Division,
CSIR-North East Institute of Science & Technology, Jorhat, Assam, India
ABSTRACT
ARTICLE HISTORY
Received 3 November 2017
A practical, straightforward, and highly efficient CuI mediated green
protocol for the regioselective synthesis of 1,4-disubstituted-1,2,
KEYWORDS
3
-triazole was developed using cetyltrimethylammonium bromide as
1,2,3-Triazoles; CTAB;
a cheap additive in good to excellent yields. Low catalyst loadings,
environmentally friendly solvent, wide substrate scope and short
reaction times at room temperature make this strategy more
accessible and safe.
CuAAC; phase transfer
catalyst; water
GRAPHICAL ABSTRACT
Introduction
1
,2,3-Triazoles are nitrogen-containing five-membered heterocycles, and an important
[
1]
structural motif owing to its significant applications in medicinal chemistry. As an
important amide isostere, the 1,2,3-triazole core demonstrates a broad spectrum of
biological activities such as antibacterial, antifungal, antiviral, antiallergic, anti-HIV, and
[
2]
antituberculosis activities and some of them are available in the market as drugs.
Furthermore, the application of 1,2,3-triazoles is also extended to other areas such as
organic synthesis, chemical biology, polymer, and materials science.[3] The 1,2,3-triazole
moiety has also exhibited as a versatile ligand for metal coordination, directing groups
for transition-metal-catalyzed C–H activation as well as industrial applications, such as
[
4]
photostabilizers, lubricants, dyes, and corrosion inhibitor. Numerous methodologies
have been developed for the synthesis of 1,2,3-triazoles so far, but the Cu(I)-catalyzed
version of Huisgen 1,3-dipolar cycloaddition reaction is undoubtedly the most powerful
[
5]
tool to furnish 1,2,3-triazole scaffolds. The Cu-catalyzed alkyne-azide cycloaddition is
an elegant and powerful protocol for the synthesis of 1,4-disubstituted 1,2,3-triazoles owing
CONTACT Diganta Sarma
University, Dibrugarh 786 004, Assam, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
dsarma22@gmail.com; dsarma22@dibru.ac.in
Department of Chemistry, Dibrugarh
1
13
Supplemental data (full experimental details, H and C NMR spectra) can be accessed on the publisher’s website.
©
2018 Taylor & Francis

2
A. A. ALI ET AL.
to its ample applicability and efficiency.[6] The typical Cu(I) catalyst was usually generated
from the cheap and easily available mixture of CuSO and sodium ascorbate and stabilized
4
[
7]
by either amine base or ligand.
In recent years, many new catalyst systems have been reported involving homogeneous
as well as heterogeneous Cu catalyst.[ Lim et al. developed a mild methodology using
8]
[9]
β-cyclodextrin as a phase transfer catalyst. Similarly, the Scarso group reported miceller
(
sodium lauryl sulfosuccinate and TPGS-750-M) promoted simple, and efficient synthesis
[
10]
of 1,2,3-triazoles in the presence of [Cu(IMes)Cl] catalyst at room temperature.
Recently, Doris et al.[11] developed an efficient nano Cu-catalyst in polydiacetylene micelles
for Huisgen cycloaddition reaction. Despite these remarkable advances, most of the
systems often used expensive additive, organic solvents, high catalyst loading, multistep
Cu-complex synthesis, long reaction time and harsh reaction conditions which limited
their practical applications. Therefore, the development of a convenient, green and efficient
method to access 1,4-disubstituted-1,2,3-triazoles is of great significance. In continuation
[
12]
of our work on 1,2,3-triazoles
herein, we wish to report a straightforward, rapid,
and economical protocol for the synthesis of 1,4-disubstituted 1,2,3-triazoles at room
temperature under environmentally friendly condition using cetyltrimethylammonium
bromide (CTAB) as an additive.
Results and discussion
We initialized the copper-catalyzed optimum cycloaddition conditions using benzyl azide
with phenylacetylene as the model substrates, as shown in Table 1. In this preliminary
experiment, the Huisgen cycloaddition reaction was performed in standard cycloaddition
conditions (t-BuOH/H O) with various Cu sources (1 mol%) as a catalyst, CTAB as an
2
additive in the air at room temperature for 1 h. We were delighted to see that the reaction
proceeded well to give in 90% yields of the desired product 3a (Table 1, entry 1).
Encouraged by this result, we have decided to screen different commercial Cu catalysts
in the cycloaddition reaction. It was revealed that CuI displayed high catalytic activities
resulting 75% conversion to the 1,4-disubstituted-1,2,3-triazole (Table 1, entry 2). It is
noteworthy that water as a solvent lead superior activity than organic solvents (Table 1,
entry 8). Developing an economic and environmentally friendly reaction using water as
solvent is undoubtedly the most favorable condition. Increasing the catalyst loading had
the expected effect of enhancing the rate of the reaction. From 1 to 10 mol%, it was possible
to notably decrease the reaction time to accomplish full conversion within 30 min (Table 1,
entry 13).When the reaction was performed in the presence of 10 mol% of CuI without
adding CTAB, the reaction did not give satisfactory result and only 45% yield of the triazole
was obtained (Table 1, entry 14). Nevertheless, 1 mol% copper catalyst affords sufficiently
rapid reaction times, making it unnecessary to rely on higher catalyst loadings to get the
desired rates. However, it is evident that no product was obtained in the absence of a
catalyst under this identical condition (Table 1, entry 16). Similarly, no byproduct was
detected under this conditions, and interestingly, 40% yield of the desired adduct was
obtained without using CTAB highlighting the role of the additive (Table 1, entry 15). It
is noteworthy that, in the presence of other surfactants such as SDS (anionic surfactant)
and Tween-80 (nonionic), the reaction led to a negligible yield of the desired triazole
(Table 1, entries 17 and 18).

SYNTHETIC COMMUNICATIONS®
3
a
Table 1. The azide-alkyne cycloaddition with different catalysts in various solvent system .
b
Entry
Catalyst
· 5H O/Na ascorbate
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
CuSO
CuI
4
2
t-BuOH/H
t-BuOH/H
t-BuOH/H
t-BuOH/H
t-BuOH/H
t-BuOH/H
t-BuOH/H
2
O
O
O
O
O
O
O
70
75
70
60
40
60
2
2
2
2
2
2
CuBr
Cu(OAc)
2
· 2H
/Na ascorbate
O/Na ascorbate
2
O
3
Cu(NO )
2
CuCl
CuO
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
–
2
· H
2
No reaction
H
2
O
95
75
70
70
50
DMSO
DMF
THF
0
1
2
3
4
5
6
7
8
Toluene
c
H
H
H
H
H
H
2
O
2
O
2
O
2
O
2
O
2
O
96
d
45
e
40
No reaction
f
CuI
CuI
30
g
35
a
Reaction condition: benzyl azide (1 mmol), phenyl acetylene (1.2 mmol), catalyst (1 mol%), CTAB (1 mol%), solvent (2 mL)
at room temperature.
Isolated yields.
b
c
CuI (10 mol%).
d
CuI (10 mol%) without adding CTAB.
In the absence of CTAB.
Instead of CTAB, SDS is used.
Instead of CTAB, tween-80 is used.
e
f
g
With the optimal conditions established, we then explored the scope of the reaction and
the results are presented in Table 2. For all the examined substrates, experiments were per-
formed efficiently to completion in short reaction times and the corresponding triazoles
were obtained in good to excellent yields. As expected, aromatic acetylenes reacted readily
with benzyl azide to form the desired triazole products in excellent yields (Table 2, entries
1
–3). Cycloaddition of phenylacetylene with functionalized benzyl azides afforded excellent
yields of 1,4-disubstituted-1,2,3-triazoles, respectively. The utility of this reaction is further
proved in aliphatic alkynes and found that they also worked well and afforded the desired
products in good yields (Table 2, entries 4 and 5). The reaction of phenethyl azide with
phenylacetylene also furnished the appropriate products with high yields (Table 2,
entry 15). In the case of aromatic azides, phenylazides with both electron-withdrawing
groups (such as halogen and CN) and electron-donating groups (such as CH and
3
OMe) were feasible substrates for this reaction affording the triazole products in excellent
yields (Table 2, entries 9–14). The extension of this protocol to a variety of reactive
functional groups such as alcohol and ester also resulted in the formation of corresponding
1
,4-disubstituted-1,2,3-triazoles in good yields (Table 2, entries 6–8).
The acceleration of copper-catalyzed azide-alkyne cycloaddition reactions by cationic
surfactant CTAB is believed to be due to the micelle formation of CTAB in water and this
micelle acts as a phase transfer catalyst. Micellar media have been broadly used to influence
the rate of various organic and inorganic reactions. The promoting effect of CTAB can be

4
A. A. ALI ET AL.
Table 2.a Cycloaddition of various azides and alkynes catalyzed by copper iodide in water and CTAB as
additive .
b
Entry
1
Azide
Alkyne
Product
Yield (%)
92
3a
2
3
4
5
6
7
3b
3c
3d
3e
3f
90
90
85
80
65
80
3g
8
9
3h
3i
90
85
10
11
12
3j
3k
3l
88
85
90
13
14
15
3m
3n
3o
90
88
80
(Continued)

SYNTHETIC COMMUNICATIONS®
5
Table 2. Continued.
b
Entry
Azide
Alkyne
Product
Yield (%)
16
17
18
3p
85
88
90
3q
3r
a
b
Reaction condition: azide (1 mmol), alkyne (1.2 mmol), CuI (1 mol%), CTAB (1 mol%), H
Isolated yield.
2
O (2 mL) at room temperature.
explained by considering both electrostatic and hydrophobic interactions of CTAB with the
reactants which work simultaneously.[13] The CTAB micellar system has positively charged
head groups at the periphery and non-polar hydrocarbon chains in its core. It allows the
apolar organic substrates to enter the same phase and bring the substrates close to one
another to drive the reaction forward. On the basis of the recent experimental mechanistic
[
14]
study by Fokin’s group,
Fig. 1).
we have proposed a plausible mechanism for this reaction
(
Figure 1. Plausible reaction mechanism.

6
A. A. ALI ET AL.
Conclusion
In conclusion, we have developed a highly efficient and straightforward protocol of
surfactant CTAB promoted CuI catalyzed regioselective synthesis of 1,4-disubstituted-
1
,2,3-triazoles in good to excellent yields from terminal alkyne and organic azides under
environmentally benign conditions. Cheap and readily available materials and mild
reaction conditions make this green strategy more attractive toward the application in
different fields of chemistry.
Experimental
General information
Reagents and solvents were purchased from different commercial sources and used without
further purification unless otherwise is noted. Purifications of products were performed by
column chromatography using silica gel (200–300 mesh). Analytical thin-layer
chromatography was performed using silica gel 60F plates and visualized with UV light.
254
1
H NMR (500 MHz), 13C NMR (125 MHz) were recorded on a Bruker Avance 500 MHz
spectrometer using TMS as an internal standard. Chemical shifts are reported in
parts per million (ppm, d) downfield from residual solvents peaks and coupling constants
are reported as Hertz (Hz). Splitting patterns are designated as: s ¼ singlet, d ¼ doublet,
t ¼ triplet, q ¼ quartet, m ¼ multiplet, etc. Melting points were determined on a Büchi
B-540 melting point apparatus.
Typical procedure for the synthesis of 1,4-disubstituted-1H-1,2,3-triazole
To a mixture of CuI (1 mol%) and CTAB (1 mol%) was added acetylene (1.2 mmol) and
azide (1 mmol) in water (2 mL) and stirred at room temperature for 1 h. After completion
of the reaction it was extracted with ethyl acetate (2 � 20 mL), washed with brine, dried
over anhydrous sodium sulfate and concentrated under vacuum, which on column
chromatography (ethyl acetate:hexanes) afforded the desired product.
1
-Benzyl-4-phenyl-1H-1,2,3-triazole (3a)
1
White solid, mp 128–130 °C, 92% yield. H NMR (500 MHz, CDCl ): δ 7.79 (d, J ¼ 5.5 Hz,
3
2
1
H), 7.66 (s, 1H), 7.41–7.29 (m, 5H), 5.57 (s, 2H), 13C NMR (125 MHz, CDCl ): δ 148.9,
34.1, 130.5, 129.0, 128.7, 128.6, 128.0, 127.9, 125.6, 119.5, and 54.3.
3
Funding
D.S. is thankful to DST, New Delhi, India for a research grant [No. EMR/2016/002345]. A.A.A.
thanks CSIR, New Delhi for Senior Research Fellowship. The financial assistance of DST-FIST
and UGC-SAP programme to the Department of Chemistry, Dibrugarh University is also gratefully
acknowledged.
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