A new synthetic protocol for one-pot preparations of 5-halo-1,4- disubstituted-1,2,3-triazoles

Article abstract of DOI:10.1071/CH11067

In this paper, a new synthetic protocol for one-pot preparations of 5-halo-1,4-disubstituted-1,2,3-triazoles is provided by rational combination of a Cu^I catalyzed azidealkyne cycloaddition (CuAAC) reaction and an oxidative halogenation reactio

Full text of DOI:10.1071/CH11067

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2011, 64, 1383–1389
A New Synthetic Protocol for One-Pot Preparations
of 5-Halo-1,4-disubstituted-1,2,3-triazoles
A B
,
A
A
A
A
Lingjun Li, Yanyan Li, Ran Li, Anlian Zhu, and Guisheng Zhang
A
College of Chemistry and Environmental Science, Henan Normal University,
Key Laboratory of Green Chemical Media and Reactions,
Ministry of Education, Xinxiang 453007, China.
B
Corresponding author. Email: lingjunlee@htu.cn
In this paper, a new synthetic protocol for one-pot preparations of 5-halo-1,4-disubstituted-1,2,3-triazoles is provided by
rational combination of a CuI catalyzed azide–alkyne cycloaddition (CuAAC) reaction and an oxidative halogenation
reaction. CuI- N-chlorosuccinimide (NCS) and CuBr-NCS reaction systems are developed, respectively, for effective
preparations of 5-iodo-1,4-disubstituted-1,2,3-triazoles and 5-bromo-1,4-disubstituted-1,2,3-trizoles under mild condi-
tions with a high tolerance of various sensitive groups.
Manuscript received: 11 February 2011.
Manuscript accepted: 2 June 2011.
Published online: 23 August 2011.
Introduction
(2) substitution reactions based on the activity of 5-H in 1,2,3-
triazoles,[25] (3) substitution by trapping the carbon anion
intermediates,[26–28] (4) transformations from 5-NH2-1,4-
disubstituted-1,2,3-triazoles,[29] and (5) by-products from CuI-
catalyzed Huisgen cycloaddition reactions.[30] But these
methods often involve rigorous reaction conditions, lead to
low yield or low chemo-selectivity, and in some cases the active
halo-alkynes or alkynylboronates have to be prepared in
advance. Recently, we found the CuI-N-bromosuccinimide
(NBS) reaction system could promote a multi-component
cycloaddition reaction to efficiently prepare 5-iodo-1,4-
disubstituted-1,2,3-triazoles directly from azides and terminal
alkynes.[27] In the CuI-NBS reaction system, NBS worked as an
oxidant to oxidize Iꢀ to Iþ in situ, and the Iþ produced in situ
attacked the 5-carbon anion of the CuAAC reaction intermediate
efficiently. Thus it is possible to combine the CuAAC reaction
and halogenation reaction in one pot. In this paper, we analyze
the potential demands of the oxidants in the combination of
the CuAAC reaction and halogenation reaction. Through
screening the oxidants, we develop a new more efficient CuI-
N-chlorosuccinimide (NCS) reaction system for the one-pot
preparation of 5-iodo-1,4-disubstituted-1,2,3-triazoles from
azide and terminal alkynes. Moreover, NCS as an oxidant can
be applied in effective one-pot preparations of 5-iodo-1,4-
substituted-1,2,3-triazoles with the CuBr-NCS reaction system.
Finally, a possible oxidation–reduction reaction mechanism is
proposed to explain the high activities of NCS as oxidant in the
CuX-NCS reaction systems in the preparation of 5-halo-1,4-
disubstituted-1,2,3-triazoles.
Recently, click chemistry has provided a simple method to build
organic molecules in high yields under mild conditions in the
presence of diverse functional groups.[1] The CuI catalyzed
azide–alkyne cycloaddition (CuAAC) is considered a typical
‘click’ reaction in which a 1,2,3-triazole is formed in very high
yields and good regioselectivity in the presence of CuI.[2,3] By
now, the CuAAC reaction has been widely used in organic
synthesis,[4,5] drug discovery,[6,7] molecular recognition,[8,9]
bioconjugation chemistry,[10,11] and polymer and materials
sciences.[12,13]
Aryl halides are important compounds in drug discovery
and synthetic chemistry.[14] For example, aryl halides can act as
reactants in several important synthetic transformations such as
Heck reactions,[15] and Suzuki[16] and Negishi cross couplings.[17]
Therefore, the combination of a CuAAC reaction and an
halogenation reaction to prepare halo-1,2,3-triazoles would
provide a novel synthetic protocol to produce structurally
diverse functional 1,2,3-triazole molecules and promising drug
candidates (Scheme 1).
Several methods have been reported for the preparation of
5-halo-1,4-disubstituted-1,2,3-triazoles: (1) specific 1,3-dipolar
cylcoadditions between substituted alkynes and azides,[18–24]
R1
N
R1
ꢀ
N
X
R2
N3
N
R2
CuAAC reaction
ꢀ
in one pot
Results and Discussion
halogenation reaction
The One-pot Preparation of 5-Iodo-1,4-disubstituted-
1,2,3-triazoles
Scheme 1. The preparation of 5-halo-1,2,3-triazole through the combina-
tion of CuI catalyzed azide–alkyne cycloaddition (CuAAC) reaction and
halogenation reaction in one pot.
In general, the direct iodination of an aromatic compound is a
relatively difficult process because of the weak electrophilicity
Ó CSIRO 2011
10.1071/CH11067

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L. Li et al.
Table 1. The preparation of 5-iodo-1,4-disubstituted-1,2,3-triazole under different catalytic systems at ambient
temperature
N
N
I
AcO
N3
N
N
O
AcO
N
N
AcO
CuBr/X
O
ꢀ
ꢀ
O
OAc OAc
OAc OAc
OAc OAc
5H-triazole
1a
2a
3a
4a
Entry
Copper(I)-OxidantA
Reaction time [h]
Isolated yield 3a (4a) [%]
1
CuI-NaClO2
CuI-NaNO2
CuI-SnCl4
12
12
12
12
12
12
12
5
–
2
–
3
–
4
CuI-PCC
–
5
CuI-DDQ
10 (32)
20 (35)
30 (31)
85 (–)
92 (–)
90 (–)
90 (–)
30 (15)
37 (15)
6
CuI-IBD
7
CuI-NIS
8
CuI-NBS
9
CuI-NCS
3
10
11
12
13
CuI(POCH3)2-NCS
CuI(PPh3)2-NCS
CuI(POCH3)2-NBS
CuI(PPh3)2-NBS
12
12
12
12
AThe mole ratio of alkyne, azide, CuI, and oxidant was 1.0 : 1.0 : 1.1, with 1.1 equiv. of N,N-diisopropylethylamine (DIPEA)
added as the alkali.
of molecular iodine.[31] Several methods have been used to
enhance the rate of the iodination reaction, with oxidative
iodination reactions being one of the most effective methods.
For example, NaI-FeCl3,[32] NaClO2/NaI,[33] air/I2/NaNO2,[34]
and KI/tert-butyl hydroperoxide[35] reaction systems have been
reported for the effective preparations of aryl iodide. In the
oxidative iodination reaction, an iodine anion or iodine mole-
cule is oxidized to Iþ in situ, and the active Iþ participates in
electrophilic substitution reactions with aryl compounds more
effectively. Therefore, the combination of an oxidative iodin-
ation reaction and a CuAAC reaction would provide an effective
method for the one-pot preparation of iodo-1,2,3-triazole.
However, the Cuþ salt in the combination reaction is easily
oxidized because of the presence of an oxidant in the oxidative
iodination reaction. If Cuþ is oxidized to Cu2þ, it will lose its
catalytic function for the 1,3-dipolar cylcoaddition between a
terminal alkyne and azide. So the oxidant used in the combina-
tion reaction should be mild and selective enough to maintain
effective oxidation of Iꢀ to Iþ, and at same time avoid the
oxidation of Cuþ to Cu2þ. Based on the above analysis, different
oxidants were investigated in the CuI-oxidant reaction systems
for the preparation of 5-iodo-1,4-substituted-1,2,3-triazoles
(Table 1).
N
N
N
AcO
CuLn
O
OAc OAc
5a
Fig. 1. The structure of carbon anion intermediate 5a in the CuI catalyzed
azide–alkyne cycloaddition (CuAAC) reaction.
efficiently trapping of the carbanion intermediate 5a (Fig. 1),
and lead to the formation of the 5-iodo-substituted products 3a.
If the oxidants cannot efficiently oxidize Iꢀ to provide active Iþ,
the proton will attack the carbon anion intermediate 5a to give
more 5-H-triazole 4a with a decrease of 5-substituted-triazole
3a. If the oxidants are too strong, they will oxidize Cuþ to Cu2þ
with loss of catalytic capability for the CuAAC reaction, and
then neither 3a or 4a can be obtained. Among all the oxidants in
Table 1, NCS shows the best chemoselectivity, it can efficiently
oxidize Iꢀ to Iþ for trapping the carbon anion intermediate 5a
(Fig. 1) to give iodo-substituted product 3a, and at the same time
it can avoid the over-oxidation of Cuþ and retain enough
catalytic Cuþ for the CuAAC reaction.
Other copper resources were also investigated for the com-
bination of the oxidative iodination reaction and CuAAC
reaction. Under the CuI(POCH3)2-NCS and CuI(PPh3)2-NCS
reaction systems, 5-iodo-1,4-disubstituted-1,2,3-triazole 3a was
obtained with desirable yields within 12 h. But under the
CuI(POCH3)2-NBS and CuI(PPh3)2-NBS reaction systems, low
From the results in Table 1, the effect of oxidants on the
distribution of products 3a and 4a are significant. With a strong
oxidant like pyridinium chlorochromate (PCC), metal ion, and
NaNO2, neither 5-H-triazole 4a nor 5-substituted-triazole 3a is
obtained. With a weak oxidant such as iodosobenzene diacetate
(IBD), 5-H-triazole 4a is the main product. The possible role
of oxidant in the CuI-oxidant catalytic system is as follows.
The oxidants in these reaction systems oxidize Iꢀ into Iþ for

Preparation of 5-halo-1,2,3-triazoles
1385
Table 2. The preparations of 5-iodo-1,4-disubstituted-1,2,3-triazole mediated by CuI-N-chlorosuccinimide (NCS) reaction system
EntryA
Azide
Alkyne
Product
Time [h]
Isolated yield [%]
I
N3
N
1
3
91
N
N
2a
1b
3a
I
MeO
N3
O
O
N
2
3
3
3
87
92
O
N
N
1b
2b
2a
3b
N
AcO
N
N
N3
O
AcO
HO
O
I
OAc
OAc
AcO OAc
1a
3c
OTBDMS
O
N
N
O
OTBDMS
N
I
HO
N3
4
5
91
2a
1c
3d
OTBDMS
O
HO
N
MeO
O
N
OTBDMS
O
HO
N
I
N3
5
5
89
1c
2b
2a
S
O
O
3e
OAc
O
AcO
AcO
OAc
O
S
N
AcO
AcO
N
N
S
I
6
5
82
N3
1d
3f
O
S P
O
S
S
P
O
O
O
HO
N3
O
O
HN
I
7
95
O
O
O
N
N
1b
HO
N
O
1e
HN
O
O
O
3g
2c
AThe mole ratio of alkyne, azide, CuI, and oxidant was 1.0:1.0:1.1, with 1.1 equiv. of N,N-diisopropylethylamine (DIPEA) added as the base.

1386
L. Li et al.
Table 3. The preparation of 5-bromo-1,4-disubstituted-1,2,3-triazoles mediated by CuBr-N-chlorosuccinimide (NCS) reaction system
EntryA
Azides
Alkynes
Products
Time [h]
Isolated yield [%]
Ph
N
AcO
N3
Br
O
N
O
AcO
N
1
8
81
OAc
OAc
2a
1a
OAc OAc
6a
AcO
N
N
N
N3
O
AcO
O
2
3
4
8
76
71
65
Br
OAc
OAc
2c
2a
2a
1a
OAc OAc
6b
OAc
O
OAc
AcO
AcO
OAc
O
OAc
AcO
AcO
N
8
N
N3
Br
N
1f
Ph
6c
O
OTBDMS
AcO
O
N
AcO
OTBDMS
N
N
Br
N3
13
1f
Ph
6d
Ph
N3
Br
Br
5
10
70
N
N
Ph
Ph
2a
2a
N
1b
6e
Ph
N
N3
6
12
65
N
N
1g
6f
MeO
AcO
N3
O
MeO
Br
O
N
7
12
60
OAc OAc
AcO
2d
N
N
1a
OAc OAc
6g
(Continued)

Preparation of 5-halo-1,2,3-triazoles
1387
Table 3. (Continued)
Alkynes
AcO
EntryA
Azides
Products
Time [h]
Isolated yield [%]
AcO
O
AcO
O
O
N3
HN
O
8
8
76
N
N
Br
O
OAc
OAc
HN
AcO
N
O
1a
OAc OAc
2e
6h
AThe mole ratio of alkyne, azide, CuI, and oxidant was 1.5:1:1.5:1.5. with 1.1 equiv. of N,N-diisopropylethylamine (DIPEA) added as the base.
yields of 3a were given within 12 h (entries 10–13 in Table 1).
NIS ꢀ CuI ꢀ Hꢀ
NBS ꢀ CuI ꢀ Hꢀ
succinimide ꢀ Cuꢀ
succinimide ꢀ Cuꢀ
ꢀ
ꢀ
I
I
So, NCS showed higher activities than NBS as an oxidant in the
CuI/ligand-oxidant reaction system for the one-pot preparation
of 5-iodo-1,4-disubstituted-1,2,3-triazoles.
I
I
Br
NCS ꢀ CuI ꢀ Hꢀ
succinimide ꢀ Cuꢀ
ꢀ
Cl
The application of this new synthetic protocol was then
explored by using various azides and alkynes as building blocks
to construct 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives
(entries 1–7 in Table 2). Different types of protective groups,
such as acetyl, ketal, PhS-, and tert-butyldimethylsilyl
(TBDMS) groups could tolerate the reaction conditions. Some
widely used functional groups like ester, ether, and amide were
also found to be intact under the CuI-NCS reaction system.
Benzyl azides also successfully reacted with corresponding
alkynes to give 5-iodo-1,4-disubstituted-1,2,3-triazoles in good
to moderate yields (entries 1–2 in Table 2). Furthermore, the
alkynes and azides in the sugar building blocks and cyclic
adenosine 500-diphosphoribose (cADPR) analogue were tried
under the CuI-NCS catalytic system (entries 3–7 in Table 2),
and the corresponding 5-iodo-1,4-substituted-1,2,3-triazoles
were successfully obtained in good yields with intact sugar
moieties.
NBS ꢀ CuBr ꢀ Hꢀ
NCS ꢀ CuBr ꢀ Hꢀ
succinimide ꢀ Cuꢀ
succinimide ꢀ Cuꢀ
ꢀ
ꢀ
Br Br
Br Cl
Scheme 2. The possible oxidation–reduction reactions between CuI
and N-iodosuccinimide (NIS), CuI and N-bromosuccinimide (NBS), CuI
and N-chlorosuccinimide (NCS), CuBr and NCS, and CuBr and NBS in the
presence of proton.
presence of proton (Scheme 2). Among all the oxidative pro-
ducts produced in situ from the reactions between CuI and NIS,
NBS, and NCS, ICl should be the most active Iþ source, and
thus the NCS-CuI reaction system should be most effective
combination for the preparation of 5-iodo-1,4-disubstituted-
1,2,3-triazole. For the bromination reaction, the BrCl species
produced in situ should be the more active Brþ source, and thus
the NCS-CuBr reaction system should be the more effective
combination for the preparation of 5-bromo-1,4-disubstituted-
1,2,3-triazoles.
The One-pot Preparation of 5-Bromo-1,4-disubstituted-
1,2,3-triazoles
Based on the results obtained with the one-pot preparation of
5-iodo-1,4-disubstituted-1,2,3-triazoles, we applied NCS as the
oxidant for the one-pot preparation of 5-bromo-1,4-disubstituted-
1,2,3-triazoles (Table 3). Under CuBr-NCS reaction systems,
terminal alkynes and azides can react smoothly at ambient
temperature, and the target products 5-bromo-1,4-disubsituted-
1,2,3-triazoles can be obtained in moderate to good yields with a
wide tolerance of sensitive groups. Furthermore, the CuBr-NCS
reaction system was also applied in the sugar building blocks
and cADPR analogues, and the target compounds 6c–d and 6h
were obtained with good yields.
Based on the above analysis about oxidative halogenation
reactions and the mechanism of the CuAAC reaction in
the literature,[4,5] a possible reaction mechanism of the CuX-
NCS mediated azide–alkyne cycloaddition reactions is
proposed (Scheme 3). There is a competitive reaction between
5-H-1,2,3-triazole and 5-halo-1,2,3-triazole. Protons attack
the carbon anion intermediate 5 to produce 5-H-1,2,3-triazole,
or Xþ attack the carbon anion intermediate 5 to produce
5-halogeno-1,2,3-triazole. In the CuX-NCS reaction system,
Xꢀ coming from CuX might be oxidized by NCS to provide
an efficient Xþ source. With an efficient Xþ source, the halo-
substitution reaction would be more competitive compared with
proton-substitution, and thus the halo-substituted product 3 or 6
will be the major product in the competitive reaction procedure.
The Possible Mechanism of the CuX-NCS for the
One-pot Preparation of 5-Halo-1,4-disubstituted-
1,2,3-triazoles
Conclusions
As oxidative halogenation reactions, the possible oxidation–
reduction reactions between CuI and NIS, CuI and NBS, CuI and
NCS, CuBr and NCS, and CuBr and NBS were proposed in the
In this paper, we study CuX-oxidant systems for the preparation
of 5-halo-1,4-disubstituted-1,2,3-triazoles by the combination

1388
L. Li et al.
Cuꢀ
ꢀ
Xꢀ
CuX ꢀ NCS
X ꢂ I, Br
N
N
Xꢀ
N
R
R
Rꢁ
N
N
Cuꢀ
Major product
X
N
3 or 6
R
N3
ꢀ
Rꢁ
R
Rꢁ
Hꢀ
N
N
CuLn
N
Rꢁ
5
4
Scheme 3. The plausible mechanism of preparation of 5-halo-1,4-disubstituted-1,2,3-triazoles with CuX-N-chlorosuccinimide
(NCS) reaction system.
of a CuAAC reaction and an oxidative halogenation reaction
in one pot. CuI-NCS was developed as the most effective reaction
system for the one-pot preparation of 5-iodo-1,4-disubstituted-
1,2,3-triazoles using mild reaction conditions with a high
tolerance of various sensitive groups. CuBr-NCS was developed
as an effective reaction system for the preparation of 5-bromo-
1,4-disubstituted-1,2,3-triazoles using mild reaction conditions.
Successful application of the CuI-NCS and CuBr-NCS reaction
systems in sugar and cADPR analogues illustrate the value of
this method in the synthesis of designed biomolecules. A pos-
sible mechanism is proposed to explain the high activities of the
CuI-NCS and CuBr-NCS reaction systems in the preparation of
5-halo-1,4-disubstituted-1,2,3-triazoles.
Acetic Acid 4-Acetoxy-2-acetoxymethyl-5-
(5-bromo-4-phenyl-[1,2,3]triazol-1-yl)-
tetrahydrofuran-3-yl Ester (6a)
dH (400 MHz, CDCl3) 7.97–7.40 (m, 5H, ArH), 6.19–6.16
(m, 2H, H-10, H-20), 5.86 (dd, J 6.8, 4.8, 1H, H-30), 4.53–4.50 (m,
1H, H-40), 4.45 (dd, J 12.4, 3,2, 1H, H-50a), 4.17 (dd, J 12.4, 3.2,
1H, H-50b), 2.17, 2.15, 2.05 (3 ꢁ s, 9H, 3OAc). dC (100 MHz,
CDCl3) 169.7, 168.5, 168.4, 144.2, 128.1, 128.0, 127.8, 126.1,
107.8, 87.6, 80.3, 73.0, 70.1, 61.8, 19.8, 19.6. HRMS (ESI) Calc.
for (M þ Naþ) C19H20BrN3O7Na: 504.0382. Found: 504.0356
(M þ Naþ).
Acetic Acid 4-Acetoxy-2-acetoxymethyl-5-(5-bromo-4-
p-tolyl-[1,2,3]triazol-1-yl)-tetrahydrofuran-3-yl Ester (6b)
dH (400 MHz, CDCl3) 7.89–7.31 (m, 4H, ArH), 6.20 (m, 2H,
H-10, H-20), 5.88 (t, J 4.8, 1H, H-30), 4.53–4.52 (m, 1H, H-40),
4.48 (dd, J 12.4, 3.2, 1H, H-50a), 4.20 (dd, J 12.4, 3.2, 1H, H-50b),
2.44 (s, 3H, CH3), 2.20, 2.18, 2.07 (3s, 9H, 3OAc). dC (100 MHz,
CDCl3) 169.7, 168.5, 144.3, 138.0, 130.8, 128.5, 126.0, 125.5,
125.2, 107.4, 87.5, 80.3, 73.0, 70.1, 61.8, 20.5, 19.8, 19.6.
HRMS (ESI) Calc. for (M þ Naþ) C20H22BrN3O7Na:
518.0539. Found: 518.0565 (M þ Naþ).
Experimental
Starting Materials
Compounds 1a and 1c–g were prepared according to the
reported procedures.[36–38]
General Procedure for Compounds 3a–g
A mixture of 1 (0.035 mmol), 2 (0.048 mmol), CuI (10 mg,
0.053 mmol), N,N-diisopropylethylamine (DIPEA, 7 mg,
0.053 mmol), and NCS (7.5 mg, 0.058 mmol) in 3 mL of
THF was stirred at room temperature. The reaction procedure
was monitored by TLC. When the reaction was complete,
the mixture was evaporated, and the residue was partitioned
between ethyl acetate and H2O. The organic layer was washed
with brine, dried over anhydrous Na2SO4, and evaporated. The
residue was purified by silica gel column chromatography to
give compound 3.
Acetic Acid 2,5-Diacetoxy-6-acetoxymethyl-
3-(5-bromo-4-phenyl-[1,2,3]triazol-1-yl)-
tetrahydropyran-4-yl Ester (6c). (a, b Isomers 1:1)
dH (400 MHz, CDCl3) 8.06–7.41 (m, 10H, ArH), 6.54 (d,
J 3.2, 1H, H-10), 6.53 (t, J 10, 1H), 6.37 (d, J 8.8, 1H, H-10), 5.97
(t, J 10, 1H), 5.36–5.28 (q, J 10, 2H), 5.09 (dd, J 11.2, 3.2, 1H),
4.90 (t, J 9.6, 1H), 4.49–4.39 (m, 3H), 4.23–4.14 (m, 3H), 2.20–
1.90 (m, 24H, 8OAc). dC (100 MHz, CDCl3) 170.6, 169.8,
169.7, 169.2, 168.9, 168.3, 167.9, 128.9, 128.7, 126.8, 126.7,
109.1, 88.7, 72.9, 70.2, 68.6, 68.1, 61.3, 59.7, 29.7, 20.7, 20.6,
20.5, 20.3. HRMS (ESI) Calc. for (M þ Hþ) C22H25BrN3O9:
554.0774. Found: 554.0732 (M þ Naþ).
General Procedure for Compounds 6a–h
Acetic Acid 4-(5-Bromo-4-phenyl-[1,2,3]triazol-1-yl)-
6-(tert-butyl-dimethyl-silany-loxy)-2-methyl-
tetrahydropyran-3-yl Ester (6d)
A mixture of 1 (0.048 mmol), 2 (0.072 mmol), CuBr (10 mg,
0.072 mmol), DIPEA (9 mg, 0.072 mmol), and NCS (9.5 mg,
0.072 mmol) in 3 mL of THF was stirred at room temperature.
The reaction procedure was monitored by TLC. When the
reaction was complete, the mixture was evaporated, and
the residue was partitioned between ethyl acetate and H2O. The
organic layer was washed with brine, dried over anhydrous
Na2SO4, and evaporated. The residue was purified by silica gel
column chromatography to give compound 6.
dH (400 MHz, CDCl3) 8.01–7.41 (m, 5H, ArH), 5.32 (t, J 9.6,
1H, H-40), 5.05 (dd, J 9.6, 1.6, 1H, H-10), 4.85–4.78 (m, 1H,
H-30), 3.72–3.65 (m, 1H, H-50), 2.78–2.70 (m, 1H, H-20b),
2.40–2.36 (m, 1H, H-20a), 1.92 (s, 3H, OAc), 1.32 (d, J 6.4,
H-60), 1.10 (s, 9H, C(CH3)3), 0.20, 0.18 (2 ꢁ s, 6H, Si(CH3)2). dC
(100 MHz, CDCl3) 168.0, 143.5, 128.5, 127.7, 126.1, 94.0, 73.1,
70.6, 58.1, 38.1, 24.8, 19.6, 17.1, 16.9, ꢀ5.0, ꢀ6.0. HRMS (ESI)
Calc. for (M þ Naþ) C22H32BrN3O4SiNa: 532.1243. Found:
532.1231 (M þ Naþ).
Compounds 3a–3g and 6e were identified using 1H and
13C NMR spectroscopy and electrospray ionization MS, and
compared with the data in the literature.[22,25]

Preparation of 5-halo-1,2,3-triazoles
1389
5-Bromo-4-phenyl-1-(1-phenyl-ethyl)-1H-
[1,2,3]triazole (6f)
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doi:10.1039/B901978M
[14] S. Patai, Z. Rappoport, in The Chemistry of Functional Groups:
Supplement D2, The Chemistry of Halides, Pseudo-Halides and
Azides, 1995, Part 1, p. 2 (Wiley: Chichester).
dH (400 MHz, CDCl3) 8.01–7.32 (m, 10H, ArH), 5.81 (q,
J 7.2, 1H, CH), 2.14 (q, J 2.8, 1H, CH3). dC (100 MHz, CDCl3)
139.8, 129.7, 128.9, 128.5, 128.4, 128.3, 126.8, 126.4, 59.9,
21.8. HRMS (ESI) Calc. for (M þ Hþ) C16H15BrN3: 328.0449.
Found: 328.0477 (M þ Hþ).
[15] (a) R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5518. doi:10.1021/
JA01022A034
(b) T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44,
581. doi:10.1246/BCSJ.44.581
[16] N. Miyaura, A. Suzuki, J. Chem. Soc., Chem. Commun. 1979, 866.
doi:10.1039/C39790000866
[17] S. Baba, E. Negishi, J. Am. Chem. Soc. 1976, 98, 6729. doi:10.1021/
JA00437A067
[18] (a) Reviews on 1,3-dipolar cycloadditions, see: W. Carruthers, in
Cycloaddition Reactions in Organic Chemistry 1990, p. 269 (Perga-
mon: Oxford).
Acetic Acid 3,4-Diacetoxy-5-[5-bromo-4-(4-methoxy-
phenyl)-[1,2,3]triazol-1-yl]-tetrahydrofuran-
2-yl-methyl Ester (6g)
dH (400 MHz, CDCl3) 7.96–7.14 (m, 4H, ArH), 6.17–6.14
(m, 2H, H-10, H-20), 5.83 (dd, J 6.0, 4.8, 1H, H-30), 4.52 (dd, 1H,
J 7.2, 4.0, H-40), 4.44 (dd, J 12.4, 3.6, 1H, H-50a), 4.16 (dd,
J 12.4, 3.6, 1H, H-50b), 2.16, 2.14, 2.04 (3 ꢁ s, 9H, 3OAc).
dC (100 MHz, CDCl3) 169.7, 169.6, 168.5, 143.4, 128.0, 127.9,
124.3, 115.0, 114.8, 107.6, 87.6, 80.4, 73.0, 70.0, 61.8, 19.8,
19.6. HRMS (ESI) Calc. for (M þ Naþ) C19H19BrFN3O7Na:
522.0288. Found: 522.0305 (M þ Naþ).
(b) K. V. Gothelf, K. A. Jorgensen, Chem. Rev. 1998, 98, 863.
doi:10.1021/CR970324E
(c) G. L’abbe´, Chem. Rev. 1969, 69, 345. doi:10.1021/CR60259A004
(d) C. Spiteri, J. E. Moses, Angew. Chem. Int. Ed. 2010, 49, 31.
Acetic Acid 2-(2-{[5-Bromo-1-(3,4-diacetoxy-5-
acetoxymethyl-tetrahydrofuran-2-yl)-1H-[1,2,3]triazole-
4-carbonyl]-amino}-ethoxy)-ethyl Ester (6h)
ˇ
[19] (a) A. Stimac, I. Leban, J. Kobe, Synlett 1999, 1069. doi:10.1055/
S-1999-2755
(b) N. Joubert, R. F. Schinazi, L. A. Agrofoglio, Tetrahedron 2005, 61,
11744. doi:10.1016/J.TET.2005.09.034
dH (400 MHz, CDCl3) 7.45 (br, 1H, NH), 6.16–6.06 (m, 2H,
H-10, H-20), 5.77–5.72 (m, 1H, H-30), 4.50–4.49 (m, 1H, H-40),
4.40 (dd, J 12, 4, 1H, H-50a), 4.24–4.22 (m, 2H, H-100), 4.16 (dd,
J 2, 4, 1H, H-50b), 3.70–3.65 (m, 6H, H-200, H-400,H-500), 2.16,
2.11, 2.06 (3 ꢁ s, 9H, 3 ꢁ OAc). dC (100 MHz, CDCl3) 170.1,
169.4, 168.5, 168.3, 157.7, 136.0, 127.9, 87.5, 86.6, 80.5, 72.9,
72.8, 70.0, 68.7, 68.1, 62.4, 61.8, 37.9, 20.0, 19.7, 19.5, 19.4.
HRMS (ESI) Calc. for (M þ Naþ) C20H27BrN4O11Na:
601.0757. Found: 601.0719 (M þ Naþ).
[20] J. E. Hein, J. C. Tripp, L. Krasnova, K. B. Sharpless, V. V. Fokin,
Angew. Chem. Int. Ed. 2009, 48, 8018. doi:10.1002/ANIE.200903558
[21] J. Huang, S. J. F. Macdonald, J. P. A. Harrity, Chem. Commun. 2009,
436. doi:10.1039/B817052E
[22] B. H. M. Kuijpers, G. C. T. Dijkmans, S. Groothuys, P. J. L. M.
Quaedflieg, R. H. Blaauw, F. L. van Delft, F. P. J. T. Rutjes, Synlett
2005, 3059.
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[23] J. Garcia-Alvarez, J. D´ıez, J. Gimeno, Green Chem. 2010, 12, 2127.
doi:10.1039/C0GC00342E
[24] B. R. Buckley, S. E. Dann, H. Heaney, Chem. – Eur. J. 2010, 16, 6278.
doi:10.1002/CHEM.201000447
Acknowledgements
[25] P. Dine´r, T. Andersson, J. Kjelle´n, K. Elbing, S. Hohmannb, M. Grøtli,
New J. Chem. 2009, 33, 1010. doi:10.1039/B818909A
[26] Y. M. Wu, J. Deng, Y. Li, Q. Y. Chen, Synthesis 2005, 1314.
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[27] L. Li, G. Zhang, A. Zhu, L. Zhang, J. Org. Chem. 2008, 73, 3630.
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[28] V. Malnuit, M. Duca, A. Manout, K. Bougrin, R. Benhida, Synlett
This study was supported by the National Natural Sciences Foundation
of China (grant no. 20802017) and Innovation Scientists and Technicians
Troop Construction Projects of Henan Province (084100510002).
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