An Efficient Copper-Catalyzed One-Pot Synthesis of 1-Aryl-1,2,3-triazoles from Arylboronic Acids in Water under Mild Conditions

Article abstract of DOI:10.1002/cjoc.201500643

A convenient method for one-pot two-step 1,3-dipolar cycloadditon reaction of arylboronic acid, sodium azide followed with terminal alkynes in the presence of 2-pyrrolecarbaldiminato-Cu(II) complexes catalyst is reported. Various 1-aryl-1,2,3-triazoles were prepared in 63%-97% yields in water at 30C without any additives and avoiding the isolation of unstable aryl azides.

Full text of DOI:10.1002/cjoc.201500643

NOTE
DOI: 10.1002/cjoc.201500643
An Efficient Copper-Catalyzed One-Pot Synthesis of
1-Aryl-1,2,3-triazoles from Arylboronic Acids in Water
under Mild Conditions
Changbo Hao, Changjian Zhou, Jianwei Xie,* Jie Zhang, Ping Liu, and Bin Dai
School of Chemistry and Chemical Enginerring/Key Laboratory for Green Processing of Chemical Engineering
of Xinjiang Bingtuan, Shihezi University, Shihezi, Xinjiang 832003, China
A convenient method for one-pot two-step 1,3-dipolar cycloadditon reaction of arylboronic acid, sodium azide
followed with terminal alkynes in the presence of 2-pyrrolecarbaldiminato-Cu(II) complexes catalyst is reported.
Various 1-aryl-1,2,3-triazoles were prepared in 63%－97% yields in water at 30 ℃ without any additives and
avoiding the isolation of unstable aryl azides.
Keywords 2-pyrrolecarbaldiminato-Cu(II) complex, 1-aryl-1,2,3-triazoles, alkyne, arylboronic acid, water
hyde, amines, and copper acetate in water,[5] demon-
strate efficient catalytic activities in various process-
es.[5,6] We recently have found that 2-pyrrolecarbal-
diminato-Cu(II) complexes are efficient catalysts for the
1,3-dipolar cycloaddition reaction of benzyl halides,
NaN3 and terminal alkynes affording the 1-benzyl-
1,2,3-triazoles in good to excellent yields in water at
room temperature.[7] In an endeavor to extend the reac-
tion scope of these copper catalysts, we herein report
2-pyrrolecarbaldiminato-Cu(II)-catalyzed synthesis of
1-aryl-1,2,3-triazoles via an one-pot reaction of aryl
boronic acids with NaN3 in water followed by a click
cyclization reaction with alkyne at 30 ℃ in air without
any additives.
Introduction
1,2,3-Triazoles compound is an important class of
N-heterocycles with wide applications in synthetic and
medicinal chemistry, material science, and polymer
chemistry.[1] They serve as versatile synthetic interme-
diates, biological intermediates, linkers and various
drugs. Several methods have been described for the
synthesis of 1,2,3-triazoles. Of these transformations,
copper-catalyzed azide-alkyne cycloaddition reaction
(CuAAC) is one of the most attractive preparation pro-
tocols for 1,4-disubstituted 1,2,3-triazoles synthesis with
high regioselectivity and under demanding reaction
conditions.[2] In general, one-pot synthesis of the 1-alkyl/
benzyl-1,2,3-triazoles is always via the in situ genera-
tion of azides from alkyl/benzyl halides and NaN3 in the
presence of the alkyne using copper-catalysts in wa-
ter/alcohol co-solvents. However, there are only a few
reports for the preparation of 1-aryl-1,2,3-triazoles di-
rectly from aryl halides, NaN3 and terminal alkynes,
which usually suffer from long reaction times even at
elevated temperature because of the slow azidonation of
aryl halides.[3] Recently, several studies have been es-
tablished for the one-pot synthesis of 1-aryl-1,2,3-tria-
zoles by using boronic acids to replace the aryl halides.[4]
Milder reaction conditions, easier working up process,
and a variety of functional groups, stability and the
lower toxicity of boronic acids are the main advantages
of these protocols.
Experimental
Materials and methods
Unless otherwise stated, all reagents were purchased
from commercial suppliers and used without further
purification. Column chromatography was performed
with silica gel (200－300 mesh) purchased from Qing-
dao Haiyang Chemical Co. Ltd. Thin-layer chromatog-
raphy was carried out with Merck silica gel GF254 plates
and visualized by exposure to UV light (254 nm). All
1
1-aryl-1,2,3-triazoles are characterized by H NMR and
13C NMR, which were compared with the previously
1
reported data. H NMR spectra and 13C NMR spectra
were recorded at room temperature on a Varian
Inova-400 instrument at 400 MHz and 100 MHz, re-
spectively.
2-Pyrrolecarbaldiminato-Cu(II) complexes, which
are synthesized by reacting the pyrrole-2-carboxal-de-
*
E-mail: cesxjw@foxmail.com; Tel.: 0086-0993-2057213; Fax: 0086-0993-2057270
Received September 7, 2015; accepted October 13, 2015; published online November 13, 2015.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201500643 or from the author.
Chin. J. Chem. 2015, 33, 1317—1320
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Hao et al.
NOTE
General procedure for the synthesis of 1,2,3-triazoles
7a－7q
complex 1 as the catalyst in water at room temperature
without any additives.
With a set of reaction conditions in hand, we then
investigated the reaction scope of this catalytic system
and its tolerance of functional groups in the case of
other arylboronic acids and other terminal alkynes, and
the results are listed in Table 2. We were pleased to find
that all the cyclization reactions were efficiently com-
pleted within 24 h and showed broad field of application
of the process and remarkable functional group com-
patibility on both reactants.
To a 25 mL Schlenk tube was charged with
Cu(II)-complex 1 (0.005 mmol), arylboronic acid (0.5
mmol), NaN3 (1.5 mmol) and water (1 mL). The
mixture was stirred at 30 ℃ and monitored by TLC
until the arylboronic acid was consumed, and then
alkyne (0.6 mmol) was added. After complete disap-
pearance of ArN3, the reaction mixture was extracted
with ethyl acetate (3×10 mL), washed with water and
brine solution, dried over anhydrous Na2SO4, and
concentrated in vacuo. The residue was purified by flash
column chromatograph on silica gel (ethyl acetate/
petroleum ether as the eluent) to provide the target
products 7a－7q.
Table 1 Cu(II)-complex-catalyzed one-pot synthesis of 1-aryl-
1,2,3-triazole from phenylboronic acid in water: optimization of
the catalytic conditionsa
(1) Cu(II)-complex (1-4)
NaN3, H2O, 30 °C, t1
B(OH)2
Results and Discussion
(2) Ph
, t2
We initiated our investigation on the model reaction
of phenylboronic acid with sodium azide followed by
treating with phenylacetylene at room temperature in
water, and the results are summarized in Table 1. It was
found that the azidonation reaction of phenylboronic
acid with NaN3 proceeded smoothly within 8 h in the
presence of the four Cu(II) complexes with 1 mol%
loading (reaction determined by TLC analysis, Entries
1－4). Subsequently, we added phenylacetylene to the
same reaction mixture and the click cyclization reaction
was completed within 3.5 h to give the 1,4-diphenyl
triazole in 70%－96% yields. The highest isolated yield
was obtained when Cu(II)-complex 1 was used as the
catalyst. Control experiment indicated that the reaction
could not occur without the Cu(II)-complex (Entry 5).
Note that decreasing the catalyst 1 loading from 1 mol%
to 0.5 mol% resulted in lower yield and longer reaction
time (Entry 6). According to the above results, the op-
timal reaction conditions of one-pot two-step reaction of
phenylboronic acid with NaN3 followed by adding phe-
nylacetylene were established using 1 mol% Cu(II)-
R
1: R = CH3
2: R = t-Bu
3: R = Ph
4: R = Bn
N
N N
Cu
N
N
N
R
N
Cu(II)-complex (1 - 4)
Catalyst
(mol%)
1 (1)
Entry
(t1＋t2)/h
Yieldb/%
1
2
3
4
5
6
8＋3.5
8＋3.5
8＋3.5
8＋3.5
8＋3.5
9＋3.5
96
82
70
92
0
2 (1)
3 (1)
4 (1)
－
1 (0.5)
77
a Reaction conditions: phenylboronic acid (0.5 mmol), NaN3 (1.5
mmol), phenylacetylene (0.6 mmol), Cu(II)-complex, H2O (1
mL), 30 ℃; b Isolated yield.
Table 2 Synthesis of 1-aryl-1,2,3-triazoles catalysed by Cu(II)-complex 1 in watera
CH3
(1) Cu(II)-complex 1
NaN3, H2O, 30 °C, t1
N
N
N
N
N
Cu
N
Ar B(OH)2
R
N
R
(2)
, t2
5
Ar
CH3
6
7
Cu(II)-complex 1
Entry
1
Product
(t1＋t2)/h Yieldb/%
Entry
10
Product
(t1＋t2)/h
Yieldb/%
81
N
N
N
N
N
N
8
3.5
96
89
9
9
＋
＋
＋
7a
7j
N
N
N
N
N
N
2
4.5 5.5
＋
11
9
9
79
OHC
Me
7b
7k
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© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2015, 33, 1317—1320

One-Pot Synthesis of 1-Aryl-1,2,3-triazoles from Arylboronic Acids in Water
Continued
Yieldb/%
Entry
3
Product
(t1＋t2)/h Yieldb/%
Entry
12
Product
(t1＋t2)/h
17＋5
N
N
N
N
N
N
4＋6
7＋3
7＋4
6＋6
9＋7
86
80
77
84
84
81
67
63
90
97
88
NC
7l
Me
7c
N
N
N
N
N
N
4
5
6
7
13
14
15
16
17
8＋4.5
8＋11
8＋6
Me
Me
7m
7d
Me
N
N
N
N
N
N
F
Me
7n
7e
N
N
N
N
N
N
MeO
7o
7f
N
N
N
N
N
N
(CH2)4CH3
8＋3.5
8＋13
EtOOC
7p
7g
N
N
N
N
N
N
Si(CH3)3
8
9
11＋11
9＋9
91
70
F
7q
7h
N
N
N
F3C
7i
a Reaction conditions: arylboronic acid (0.5 mmol), NaN3 (1.5 mmol), acetylene (0.6 mmol), Cu(II)-complex (0.005 mmol), H2O (1 mL),
30 ℃. b Isolated yield.
The arylboronic acids bearing either electron-
donating groups (such as Me and MeO) or electron-
withdrawing groups (such as COOEt, F and CF3) un-
derwent the title transformation to afford the corres-
ponding 1,2,3-triazoles in good to excellent yields
without the need to isolate and purify the intermediate
aryl azides (Entries 1－9). ortho-Methyl and 2,6-dime-
thyl phenylboronic acids also reacted well under the
standard conditions and 80% and 77% yields were ob-
tained (Entries 4 and 5). Notably, a variety of functional
groups, such as vinyl, aldehyde and cyano, in the para-
position of phenylboronic were fully tolerated and pro-
duced the desired products in 81%, 79% and 81% yields,
respectively (Entries 10－12). For terminal alkynes, the
aliphatic alkynes seemed to be more reactive than aryl
alkynes (Entries 13－17). For example, the reaction of
n-heptyne provided the highest yield and shortest reac-
tion time in all substrates (Entry 16).
Conclusions
In summary, we have developed an efficient 2-pyr-
rolecarbaldiminato-Cu(II) complexes-catalyzed method
for one-pot two-step synthesis of 1-aryl-1,2,3-triazoles
from aryl boronic in water at 30 ℃ with 1 mol% cata-
lyst loading and without any additives. Various aryl-
boronic acids and alkynes could react well to produce
the target products in good to excellent yields. The ad-
vantages of this protocol include good substrate gener-
ality, high yields, the use of stable and easily synthe-
sized Cu(II)-complex catalyst under environmental-
friendly conditions, and experimental ease.
Acknowledgement
The authors gratefully thank the National Basic Re-
search Program of China (973 Program, No.
Chin. J. Chem. 2015, 33, 1317—1320
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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Hao et al.
NOTE
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