Copper-doped silica cuprous sulfate (CDSCS) as a highly efficient and new heterogeneous nano catalyst for [3+2] Huisgen cycloaddition

Article abstract of DOI:10.1016/j.tet.2012.07.032

The synthesis and characterization of copper-doped silica cuprous sulfate (CDSCS) as a new and efficient heterogeneous nano catalyst are described. CDSCS has been fully characterized by different microscopic, spectroscopic and physical techniques, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic forced microscopy (AFM), X-ray diffraction (XRD), inductively coupled plasma (ICP) analysis, thermogravimetric analysis (TGA) and FT-IR. CDSCS is proved to be a useful heterogeneous nano catalyst in Cu(I)-catalyzed 'Click' cycloaddition of organic azides with terminal alkynes. CDSCS catalyzes the 1,3-dipolar cycloaddition reactions of β-azido alcohols and alkynes at room temperature, in THF/H₂O (1:1, v/v) solution. Using CDSCS, 1,4-disubstituted 1,2,3-triazole adducts are mainly obtained, in good to excellent yields and in short reaction times. These compounds have featural resemblance to β-adrenoceptor blocking agents. CDSCS was approved as a chemically and thermally stable nano catalyst that can be reused for many consecutive trials without a significant decline in its reactivity.

Full text of DOI:10.1016/j.tet.2012.07.032

Tetrahedron 68 (2012) 7812e7821
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journal homepage: www.elsevier.com/locate/tet
Copper-doped silica cuprous sulfate (CDSCS) as a highly efficient and new
heterogeneous nano catalyst for [3þ2] Huisgen cycloaddition
,
a
,
b
Mohammad Navid Soltani Rad a , Somayeh Behrouz , Mohammad Mahdi Doroodmand ,
*
*
Abdollah Movahediyan a
a Department of Chemistry, Shiraz University of Technology, Shiraz, PO Box 71555-313, Iran
b Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 May 2012
Received in revised form 16 June 2012
Accepted 10 July 2012
Available online 20 July 2012
The synthesis and characterization of copper-doped silica cuprous sulfate (CDSCS) as a new and efficient
heterogeneous nano catalyst are described. CDSCS has been fully characterized by different microscopic,
spectroscopic and physical techniques, including scanning electron microscopy (SEM), transmission
electron microscopy (TEM), atomic forced microscopy (AFM), X-ray diffraction (XRD), inductively cou-
pled plasma (ICP) analysis, thermogravimetric analysis (TGA) and FT-IR. CDSCS is proved to be a useful
heterogeneous nano catalyst in Cu(I)-catalyzed ‘Click’ cycloaddition of organic azides with terminal al-
kynes. CDSCS catalyzes the 1,3-dipolar cycloaddition reactions of b-azido alcohols and alkynes at room
temperature, in THF/H2O (1:1, v/v) solution. Using CDSCS, 1,4-disubstituted 1,2,3-triazole adducts are
mainly obtained, in good to excellent yields and in short reaction times. These compounds have featural
Keywords:
Heterogeneous catalyst
Click cycloaddition
CDSCS
resemblance to b-adrenoceptor blocking agents. CDSCS was approved as a chemically and thermally
b-Azido alcohols
stable nano catalyst that can be reused for many consecutive trials without a significant decline in its
Alkyne
reactivity.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
Meldal,13 accelerates the reaction rate up to 107 times. High toler-
ance of different functionalities under mild conditions is observed
1,2,3-Triazole derivatives are important compounds in medici-
nal chemistry owing to their wide applications in drug discovery.
They can readily associate with biologically targets through the
hydrogen bonding and dipole interactions.1 The 1,2,3-triazole core
is a key structural motif in many bioactive compounds, exhibiting
a broad spectrum of biological activities, such as antiviral,2 anti-
cancer,3 anti-HIV,4 antibiotic,5 antibacterial,6 and antimicrobial.7
Additionally, they have found significant industrial applications as
dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and
photographic materials.8
Huisgen 1,3-dipolar azideealkyne cycloaddition is traditionally
applied for accessing 1,2,3-triazoles.9 However, the major limita-
tions of this non-catalyzed process are the requirement of high
temperature and poor regioselectively giving a mixture of 1,4- and
1,5-disubstituted triazoles. Up to now, several efforts to control the
1,4- versus 1,5-regioselectivity have been reported.10 As a prototype
for click chemistry,1b,11 the recent advance in Cu(I)-catalyzed azi-
deealkyne cycloaddition (CuAAC) reported by Sharpless12 and
when CuAAC protocol is employed. Furthermore, remarkable
regioselectivity is observed for 1,4-disubstituted 1,2,3-triazoles.
Active copper(I) as the catalytic species can be in situ prepared by
reduction of copper(II) salts,14 oxidation of copper(0),15 or cop-
per(II)/copper(0) comproportionation.14,16 Due to the inherent
thermogravimetric instability, and the formation of undesired
alkyneealkyne homo-coupling side products, the use of cuprous
salts in their simple form was limited.17 Nevertheless, nitrogen- or
phosphorus-based ligands are known to protect the metal center
from oxidation and disproportionation. The use of these ligands
usually causes an enhancement of cuprous-catalytic activity.18
Moreover, immobilized copper species on various solid supports,
such as charcoal,19 amine-functionalized polymers,20 zeolites,21
aluminum oxyhydroxide nanofiber,22 Wyoming’s montmorillon-
ite,23 alumina,24 silica-supported N-heterocyclic carbene,25 amine-
functionalized silica,26 and silica gel27 have been reported. How-
ever, the application of the immobilized catalysts on solid supports
frequently suffer from many disadvantages, such as requiring
additives, desorption from solid support surface and also low
reactivity of the catalyst.19a,21
* Corresponding authors. Tel.: þ98 711 7261392; fax: þ98 711 7354523; e-mail
addresses: soltani@sutech.ac.ir, navid_soltani@yahoo.com (M.N. Soltani Rad), beh-
rouz@sutech.ac.ir (S. Behrouz).
b
-Adrenoreceptor antagonists are used clinically for various
cardiovascular disease remedies.28 With the exception of a few
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.032

M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
7813
arylethanolamines (1), virtually all the clinically approved
b
-adre-
For the preparation of CDSCS, the suspension of SSA in demin-
eralized water was primarily exposed to ultrasonic irradiation at
room temperature for 1 h. Then, an enriched solution of CuI with
NaI (see the Experimental section) was mixed with SSA and the
mixture exposed to ultrasonic irradiation for 6 h at ambient tem-
perature. Filtration followed by washing and dehydration provided
CDSCS as a dark-powdered solid.
noceptor antagonists contain an aryloxypropanolamine scaffold (2)
(Fig. 1).29 Considering the remarkable therapeutic activities of tri-
azole derivatives, we incorporated the triazole cores instead of
amine-derived moieties in compounds 2 to obtain the new
b
-hydroxytriazoles 3.
To justify that copper is bonded as a cuprous sulfate in CDSCS
rather than absorbed cuprous iodide on silica, we achieved two
complementary experiments. First, it was demonstrated that re-
leasing HI could be considered as an appropriate criterion for ex-
changing the Cuþ with Hþ. For this purpose, the pH of a suspension
solution of SSA (0.001 g in 500 mL demineralized water) was found
to be 3.52. When the solution of CuI (0.05 M, 100 mL) was added,
the pH changed to 3.38. The decrease in the pH value of SSA solu-
tion after adding the CuI solution reveals the exchange of Hþ with
Cuþ, and the formation of HI. In a second experiment, for further
confidence about bonding of Cuþ in CDSCS, the well-washed and
well-sonicated (400 Watt, 50 min in deionized water) catalyst
(0.026 g) was refluxed in a Ag(I) solution (0.01 M, 100 mL) for al-
most an hour in ambient temperature. This process led to the
exchange of the Cu(I) with Ag(I). According to the obtained results
from inductively coupled plasma (ICP) technique, more than 98% of
the bonded Cu(I) was exchanged by Ag(I). This can be considered as
an evidence for formation of CDSCS using the recommended
procedure.
OH
OH
N
OH
N
N
NR2R3
O
NR2R3
R2
R1
R1
R1
1
3
2
Fig. 1. The general structure of two famous classes of
(1 and 2) and their 1,2,3-triazolyl analogues (3).
b-adrenergic blocking agents
In continuation of our interest in the design and synthesis of
new compounds having structural similarity to b-adrenoreceptor
antagonist analogues,30 we disclose the synthesis and character-
ization of CDSCS. This catalyst has been employed in [3þ2] Huisgen
cycloaddition between structurally diverse terminal alkynes and
b
-azido alcohols in H2O/THF (1:1, v/v) at room temperature. Using
CDSCS, the target compounds 3 were obtained in good to excellent
yields (Scheme 1).
(a)
O2 (8%) in Ar
SiO2
SiO2 OH
400 C, 1h
°
2.2. Characterization of catalysis nanostructure
r.t.
SiO2 OH +
SiO2 OSO H HCl
ClSO3H (neat)
+
Silica Sulfuric Acid (SSA)
3
Figs. 2e4 indicate the scanning electron microscopy (SEM),
transmission electron microscopy (TEM), and atomic force mi-
/H2O,1h,r.t.
1) Ultrasound
SiO2 OSO Cu
Hl
+
SiO2 OSO3H
3
2)
CuI/H2O,Ultrasound
/H2O,6h,r.t.
CDSCS
(b)
R1
N
OH
OH
N
N
CDSCS
H2O/THF (1:1), r.t.
R2
R2
R1
N3
+
3a-o
R1 = alkyl, alkoxy, aryloxy
R2 = ArOCH2, Ph, (Me)2COH,
N CH2
Scheme 1. (a) Routes to prepare the nano copper-doped silica cuprous sulfate (CDSCS),
(b) synthesis of new -blocking analogues 3aeo using CDSCS.
b
2. Results and discussion
2.1. Preparation of CDSCS
Fig. 2. Scanning electron microscopy (SEM) image of CDSCS.
The process for the preparation of CDSCS is shown in Scheme 1a.
As is shown in Scheme 1a, the synthesis of CDSCS was achieved
from freshly prepared silica sulfuric acid (SSA). The preparation of
SSA was previously reported by mixing the normal SiO2 and
ClSO3H.31 However, in our experience, a more satisfactory result is
obtained when activated SiO2 is used to react with ClSO3H. In this
context, the silica was first activated by a flow of 8% O2 in an argon
atmosphere for 1 h at 400 ꢀC in a furnace. Activation of SiO2 using
O2 at high temperature, leads to the formation of various defects in
the silica support.32 Then, the adequate amounts of ClSO3H were
mixed to active SiO2. A slight excess of ClSO3H (2.3 g, 0.02 mol of
ClSO3H for 60 g of SiO2) was added to freshly prepared SSA to en-
sure the enrichment of all active sites (i.e., OH) on the parent SiO2.
No further HCl gas was evolved at this stage, which is the indication
of full sulfonation. The amount of Hþ in SSA was determined by
simple acidebase back-titration and the amount of Hþ in SSA was
evaluated to 0.05 g (0.13 mmol) of silica sulfuric acid.33
croscopy (AFM) images of CDSCS, respectively. Good correlation
was observed for copper nanoparticles characterized by different
microscopic techniques. In addition, the histogram (Fig. 5) presents
the frequent distribution of CDSCS based on the AFM image (Fig. 5).
Regarding this histogram, the maximum distributed diameter for
the CDSCS is around 25 nm. The X-ray diffraction (XRD) pattern of
CDSCS is also shown in Fig. 6. Based on the XRD pattern, the strong
peaks correspond to copper nanostructure. The related data to XRD
pattern are summarized in Table 1.
Due to the results in Table 1, the peak corresponded with the
plane of (111) indicates the copper(0) formation concerned with
the disproportionation reaction of Cu(I) in a polar solution.
The copper nanoparticle size was also recognized from X-ray
line broadening using the DebyeeScherrer formula as: D¼0.9
l/ß1/2
cos . In this formula, D, , ß1/2 and are the average crystalline size,
q
l
q

7814
M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
650
550
450
350
250
150
50
20
30
40
50
60
70
80
90
100
2-Theta-Scale
Fig. 6. Smoothed X-ray diffraction (XRD) pattern of CDSCS.
Table 1
Analysis of XRD patterns related to CDSCS after reusing for three times
Fig. 3. Transmission electron microscopy (TEM) image of CDSCS.
2-Theta-scale (2
q)
Matrix and morphology
Reference
Cu
Cu(I)
19
25.5
30.5
38.5
57.2
68.5
72.1
d
(111)
(200)
(220)
(222)
(331)
(420)
19a
19a
20
d
(111)
d
20
d
21
d
a good agreement with the results attained by the microscopic
techniques.
The Fig. 7 indicates the thermogravimetric analysis (TGA) of
CDSCS. Based on the TG thermogram, a decrease in weight of CDSCS
is observed at temperature around 95 ꢀC and it is attributed to
desorption of water and other species from CDSCS. The decrease
in weight is also observed around 230 ꢀC, which is related to
desorption of sulfur from CDSCS and formation of sulfur dioxide.35
100
80
60
40
20
0
Fig. 4. Atomic force microscopy (AFM) image of CDSCS.
the applied X-ray wavelength, the angular line width at half max-
imum intensity and the Bragg’s angle, respectively.34
Regarding the peak of copper nanoparticles and the corre-
ꢀ
sponded plane of copper (200) for
l
¼1.085 A, the average size of
copper nanoparticles is estimated at around 28 nm. This value is in
55
255
455
655
855
1055
1255
Temperature (oC)
Fig. 7. Thermogravimetric (TG) analysis of CDSCS.
In addition, the increase in weight around 380 ꢀC is attributed to
the oxidation of nano copper-particles and the formation of copper
oxides.36 The sharp decrease in weight at 850 ꢀC is assigned to the
decomposition of the silica matrix. Finally, the last part of the
thermogram (the obtained flexure at the low weight percentages)
indicates the quantity of copper oxide as well as the amount of
copper nanoparticles on silica. The estimated value of copper
nanoparticles was 6.12%.
The FT-IR spectrum of the CDSCS catalyst is shown in Fig. 8. The
catalyst is solid and the solid-state IR spectrum was recorded by the
KBr disk technique. Metal oxides generally give absorption bands
below 1000 cmꢁ1, therefore an asymmetric band at 551 cmꢁ1
Fig. 5. Histogram representing the average diameter of CDSCS.

M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
7815
promotion of cycloaddition reaction. The best result obtained when
the cycloaddition reaction was conducted at 100 ꢀC for 1 h (Table 2,
entry 5). However, increasing the temperature up to 200 ꢀC did not
affect the reaction yield.
In order to optimize the reaction conditions, the influence of
various 1:1 (v/v) organic solvents/H2O was examined in the pres-
ence of CDSCS at room temperature (Table 3).
Table 3
Influence of various solvents on conversion of 1-azido-3-(naphthalen-2-yloxy)
propan-2-ol into 3a using CDSCS at room temperaturea
Fig. 8. FT-IR spectrum of freshly prepared CDSCS.
corresponds to the CueO bond. Furthermore, a band at 671 cmꢁ1 is
assigned to SeO stretching. A major broad-sharp peak lies at
900e1200 cmꢁ1 and is overlapped by several signals, including
stretching symmetric and anti-symmetric SieOeSi, asymmetric
and symmetric stretching modes of O]S]O and also symmetric
band of Cu(I or II)eO bonds.37 The bands at 1500e1700 cmꢁ1 cor-
respond to water molecules adsorbed on CDSCS and a combination
of the CDSCS vibration modes. The spectrum also shows the ab-
sorption around 3441 cmꢁ1, which is assigned to stretching vibra-
tion of different types of hydroxyl groups.
Entry
Solventb
Time (h)
Yieldc (%)
1
2
3
4
5
6
7
8
9
H2O/DMSO
H2O/DMF
H2O/t-BuOH
H2O/MeCN
H2O/THF
H2O/dioxane
H2O/toluene
H2O/acetone
H2O
0.75
0.75
2
4
0.5
3
5
5
4
4
88
84
70
50
93
63
41
52
45
62
10
THF
a
Reaction condition: 1-azido-3-(naphthalen-2-yloxy)propan-2-ol (0.01 mol),
2-(prop-2-ynyl) isoindoline-1,3-dione (0.012 mol), CDSCS (0.05 mol %), solvent
(20 mL), room temperature.
2.3. ‘Click’ cycloaddition of azides with terminal alkynes us-
ing CDSCS
b
For entries 1e8, a mixture of 1:1 (v/v) solvents were used.
c
Isolated yield.
After synthesis and characterization of CDSCS, we applied this
catalyst in synthesis of new 1,2,3-triazole derivatives. The first step
of this synthetic approach was started by optimizing the reaction
conditions. At first, we carried out the cycloaddition reaction of 2-
(prop-2-ynyl) isoindoline-1,3-dione and 1-azido-3-(naphthalen-2-
yloxy)propan-2-ol as a model reaction to acquire the correspond-
ing 1,2,3-triazole (3a).
The 1,3-dipolar cycloaddition of model reaction was carried out
in the presence of CDSCS (0.3 g, 0.05 mol %) in H2O at room tem-
perature, which was afforded 3a in 45% yield after stirring for 4 h
(Table 2, entry 1). To study the influence of temperature, the model
reaction was carried out at different temperatures (Table 2, entries
2e8). Due to Table 2, an increase in the temperature resulted in the
From Table 3, it is well demonstrated the solvent has a signifi-
cant role in progress of reaction. Among the examined solvents,
a solution of THF/H2O (1:1, v/v) (Table 3, entry 5) afforded the best
result. Moreover, equal ratio solutions of other solvents in water,
such as the solution of DMSO (Table 3, entry 1) and/or DMF (Table 3,
entry 2) also yielded the product in reasonable time. Employing the
other mixtures afforded a moderate yield of product over longer
periods of time (2e5 h). Additionally, when water and THF were
used alone, the yields of 45% and 62% for 3a were obtained after 4 h,
respectively (Table 3, entries 9 and 10). The low yield obtained for
3a using water, is attributed to lack of organic solubility in H2O.
The optimized stoichiometric ratio of azide/alkyne found to
1:1.2 for 3a when 0.05 mol % of catalyst was applied. It is important
to use an equimolar ratio of azide/alkyne. The use of large quanti-
ties of alkyne can lead to the appearance of by-products because of
alkyneealkyne homo-coupling in the presence of Cu(I) salts.
To illustrate the scope of this method, we extended the opti-
mized reaction condition to other azides and alkynes cycloaddi-
tions (Table 4). As the results in Table 4 indicate, CDSCS proved to be
useful nano catalyst for [3þ2] Huisgen cycloaddition between the
Table 2
Influence of various temperatures on conversion of 1-azido-3-(naphthalen-2-yloxy)
propan-2-ol into 3a using CDSCS in H2Oa
structurally diverse
b-azido alcohols and alkynes. Using CDSCS,
Entry
Temperature (ꢀC)
Time (h)
Yieldb (%)
compounds 3aeo were regioselectively synthesized as 1,4-
disubstituted 1,2,3-triazoles in excellent yields and short reaction
1
2
3
4
5
6
7
8
25
50
80
4
45
60
69
73
78
79
79
80
2.5
1.75
1.25
1
1
1
times. The internal alkyne was inactive toward
(Table 4, entry 16).
b-azido alcohols
90
100
110c
150c
200c
Additionally, the influence of time on the progress of reaction
for model substrates was investigated (Table 5). As the results in
Table 5 indicate, the reaction procedes smoothly and the best result
was obtained when the reaction was terminated after 0.5 h. Pro-
longing the reaction time had no distinguishable effect on the
progress of the reaction.
1
a
Reaction condition: 1-azido-3-(naphthalen-2-yloxy)propan-2-ol (0.01 mol),
2-(prop-2-ynyl) isoindoline-1,3-dione (0.012 mol), CDSCS (0.05 mol %), H2O
(20 mL), room temperature.
b
To investigate the catalytic potency of CDSCS in the 1,3-dipolar
cycloaddition, we tested the model reaction using other reported
Isolated yield.
Sealed tube was used.
c

7816
M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
Table 4
CDSCS-catalyzed ‘click’ cycloaddition of b
-azido alcohols with alkynesa
Entry
b
-Azido alcohol
Alkyne
Product 3b
Time (h)
0.5
Yieldc (%)
Conversione (%)
N
OH
N
N
O
N
OH
O
O
O
N
N3
1
93
100
O
3a
O
N
OH
N
N
O
N
OH
O
O
O
N
N3
2
3
0.5
92
83
100
92
O
MeO
MeO
O
3b
3c
N
OH
N
N
O
N
O
OH
O
O
Me
O
Me
O
N3
N
N
N
N
1
N
N
MeO
N
N
MeO
Me
Me
N
N
OH
OH
O
O
O
O
N
N3
Me
O
Me
N
N
N
N
4
5
1
1
80
81
90
90
Cl
Cl
N
O
N
N
Me
3d
Me
Me
Me
O
N
OH
N
N
O
Me
O
Me
O
N
N
N
N
OH
N3
N
N
N
N
Me
Me
3e
N
OH
N
N
OH
O
O
N
N
O
O
N3
N
N
6
7
0.75
0.5
85
91
93
3f
N
OH
N
N
OH
OH
N
N
O
N3
100
O
O
O
3g
O
N
OH
N
N
O
O
N
N
O
8
9
0.5
93
88
100
95
O
N3
O
3h
O
N
Cl
OH
N
N
Cl
OH
O
N3
O
0.33
Cl
O
O
Cl
Cl
Cl
3i
N
N
OH
OH
O
N
O
N3
10
11
O
0.33
0.33
86
90
95
Cl
Cl
Ph
Ph
3j
N
OH
N
N
OH
N3
O
100
O
NO2
NO2
3k
N
N
N
OH
OH
O
O
N3
12
0.5
88
96
3l

M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
7817
Table 4 (continued )
Entry
b
-Azido alcohol
Alkyne
Product 3b
Time (h)
0.5
Yieldc (%)
87
Conversione (%)
N
OH
N
N
OH
O
13
96
O
N3
3m
Me
Me
N
N
N
OH
OH
Me
O
O
N3
14
15
Me
0.33
91
100
HO
Ph
OH
Ph
3n
Me
Me
N
N
OH
OH
Me
Me
OH
O
N3
O
N
0.33
90
100
HO
3o
OH
Ph
O
N3
16
NRd
36
d
d
Cl
N
N Ph
Me
a
Reaction condition:
b
-azido alcohol (0.01 mol), alkyne (0.012 mol), CDSCS (0.05 mol %), THF/H2O (1:1, 20 mL), room temperature.
b
c
All products were characterized by 1H and 13C NMR, IR, CHN, and MS analysis.
Isolated yield.
No reaction.
GC yield.
d
e
Table 5
Table 6
Influence of time on conversion of 1-azido-3-(naphthalen-2-yloxy) propan-2-ol into
Comparison of various copper catalysts with CDSCS on conversion of 1-azido-3-
3a using CDSCS at room temperaturea
(naphthalen-2-yloxy) propan-2-ol into 3aa
Entry
Time (h)
Yieldb (%)
Conversionc (%)
EntryRef.
Copper catalyst
CDSCS
Cu(OAc)2
Time (h)
Yieldb (%)
1
2
3
4
5
6
0.1
0.2
0.3
0.4
0.5
0.7
45
60
75
82
93
93
53
71
85
93
100
100
1
0.5
8
7
8
1
93
73
84
80
87
238
313
412
519b
c
CuI
CuSO4$5H2Oc
Cu/C
a
Reaction condition: 1-azido-3-(naphthalen-2-yloxy)propan-2-ol (0.01 mol),
2-(prop-2-ynyl) isoindoline-1,3-dione (0.012 mol), copper catalyst (0.05 mol %),
THF/H2O (1:1, 20 mL), room temperature.
a
Reaction condition: 1-azido-3-(naphthalen-2-yloxy)propan-2-ol (0.01 mol),
2-(prop-2-ynyl) isoindoline-1,3-dione (0.012 mol), CDSCS (0.05 mol %), THF/H2O
(1:1, 20 mL), room temperature.
b
Isolated yield.
b
c
Isolated yield.
GC yield.
The reaction was carried out in the presence of sodium ascorbate (0.1 mol %).
c
alcohols used in these experiments were pre-synthesized by the
regioselective ring opening reaction of corresponded epoxides with
sodium azide, whereas the majority of terminal alkynes were
prepared via SN2-type reaction of propargyl bromide and corre-
sponded nucleophiles.
copper catalysts under the optimized condition. The comparative
results are summarized in Table 6. According to the results in Table
6, a higher yield of 3a and shorter reaction time were obtained
using CDSCS (Table 6, entry 1) in comparison with other examined
copper catalysts. Using the other catalysts afforded the satisfactory
results of 3a, however the reactions were required longer reaction
times.
Biological activities of all compounds are under studying and
will be reported elsewhere.
All synthesized compounds 3aeo were fully characterized, and
their structures were confirmed by 1H and 13C NMR, elemental
analysis, mass spectrometry and IR spectroscopy methods. Struc-
2.4. The reusability of CDSCS
tural assignments of
b-hydroxytriazoles 3kem were made by
The reusability of the CDSCS was studied during the synthesis of
3a (Table 7). In this context, prior to use and also final testing of the
catalyst for determination of its activity in many subsequent runs,
the catalyst was recycled from the reaction mixture through a sin-
tered glass funnel (vacuum-filtering). The catalyst was then washed
successively with THF/H2O (1:1, v/v, 5ꢂ10 mL) and dried in a vac-
uum oven at 100 ꢀC for 30 min. The catalyst was tested for five
consecutive runs and through each run, no fresh catalyst was
added.
comparison of their 1H NMR and 13C NMR spectra with those
reported in the literature.39 In general, the 1H NMR spectra of all
compounds confirm the presence of a singlet peak relating to res-
onance of a proton in the 5-position of the 1,2,3-triazole rings.
The chemistry works well with various
volving aryloxy, alkoxy and alkyl residues, and also tolerates a wide
spectrum of electron-donating and electron-withdrawing func-
b-azido alcohols in-
tional groups in both alkyne and azide molecules. Most of b-azido

7818
M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
Table 7
(0.063e0.200 mm, 70e230 mesh, ASTM). Melting points were
The reusability of CDSCS in successive trails for synthesis of 3aa
€
measured using a Buchi-510 apparatus in open capillaries and are
uncorrected. IR spectra were obtained using a Shimadzu FT-IR-
8300 spectrophotometer. 1H and 13C NMR spectra were obtained
€
using a Bruker Avance-DPX-250 spectrometer operating at 250/
62.5 MHz, respectively (d in parts per million, J in hertz). GC/MS
were performed on a Shimadzu GC/MS-QP 1000-EX apparatus (m/
z, rel %). Elemental analyses were conducted on a PerkineElmer
240-B micro-analyzer.
Run no.b
Time (h)
Yieldc (%)
1
2
3
4
5
0.5
0.5
1
1.25
1.5
93
93
86
84
80
The TG of CDSCS was analyzed using a lab-made thermogravi-
metric (TG) analyzer instrumentation system (Model: Q500). The
Transmission electron microscopy was employed using TEM
(CN-10, Philips, 100 kV). The scanning electron micrograph was
attained using SEM (XL-30 FEG, Philips, 20 kV) instrument. An
atomic force microscopy (AFM, DME-SPM, version 2.0.0.9) was also
used for AFM image. Spectroscopic techniques, such as inductively
coupled plasma (ICP) and patterned X-ray diffraction (XRD, D8
a
Reaction condition: 1-azido-3-(naphthalen-2-yloxy)propan-2-ol (0.01 mol),
2-(prop-2-ynyl) isoindoline-1,3-dione (0.012 mol), recovered CDSCS, THF/H2O
(1:1, 20 mL), room temperature.
b
The entry number corresponds to the trial number.
Isolated yield.
c
€
Advance, Bruker AXS) were employed for characterization of
CDSCS.
As the results in Table 7 indicate, the catalyst can be reused for
many consecutive runs without considerable decrease in its cata-
lytic reactivity. To prove the recoverability, thermal and chemical
stabilities of CDSCS, analytical techniques, such as ICP and TGA
instrument were used to measure the copper amounts before and
after five successive runs of CDSCS. Based on the ICP results, the
amount of copper bonded on fresh CDSCS was evaluated to 6.12%.
This value was also calculated to 6.14% base on TG analysis. The
small difference between obtained results from ICP and TGA anal-
yses is attributed to sample pretreatment before ICP analysis. On
the basis of the ICP results, the amount of copper species was di-
minished to 6.11% after five sequential reuses. Additionally, the ICP
analysis has endorsed the recoverability of CDSCS without signifi-
cant desorption from the silica matrix. As it is well indicated, the
amount of leached copper from CDSCS is negligible (0.01% after five
runs) and it is reasoned that this is due to strong ionic bonds
present between copper cations and sulfate group on surface of
SSA. These characteristics of CDSCS demonstrate its superiority in
comparison with usual catalysts, which are normally prepared by
immobilization of copper species on solid supports and/or
polymers.
4.2. Catalyst preparation
For preparation of CDSCS, 3.0 g of SSA was dispersed in 50 mL
of deionized water. Then, the suspension was sonicated for 1 h
in a beaker inside a sonication bath (frequency 100 MHz, 80 W)
at ambient temperature. The suspension was left for about
30 min to be deposited and separated. A solution of 1.0 mM of
copper(I) iodide in water was prepared by dissolving CuI in
triply distilled water (100 mL) and it was enriched by addition of
10 mL of NaI (0.02 M). Then, this solution was dropwise added to
the SSA, while the suspension was sonicated in a beaker inside
a sonication bath (frequency 100 MHz, 80 W) at ambient tem-
perature. The CDSCS was filtered from the suspension mixture
and was subsequently washed by distillated water (3ꢂ10 mL).
The CDSCS was then dried in vacuum at 80 ꢀC and stored in
a desiccator.
4.3. Catalytic test
To a round bottom flask (50 mL), was added a mixture of alkyne
(0.012 mol), CDSCS (0.3 g, 0.05 mol %) and the appropriate b-azido
3. Conclusions
alcohol (0.01 mol) in a mixture of THF/H2O (1:1 v/v, 20 mL). The
reaction mixture was stirred at room temperature until TLC mon-
itoring indicated no further progress in the conversion. The catalyst
was filtered off, washed with THF/H2O (5ꢂ10 mL) and the filtrate
was evaporated under vacuum to remove the solvent. The
remaining foam was dissolved in CHCl3 (100 mL) and subsequently
washed with water (2ꢂ100 mL). The organic layer was dried
(Na2SO4) and evaporated. The crude product was purified by col-
umn chromatography on silica gel and eluted with proper solvents.
Characterization data of all synthesized compounds are described
below.
In conclusion, we explained the synthesis and characterization
of nano copper-doped silica cuprous sulfate (CDSCS). CDSCS proved
to be a highly efficient heterogeneous catalyst for the regioselective
synthesis of 1,4-disubstituted 1,2,3-triazoles derivatives. In this
synthetic methodology, CDSCS catalyzes 1,3-dipolar Huisgen cy-
cloaddition of different functionalized
in a (1:1, v/v) solution of THF/H2O at room temperature. Good to
excellent yields of -hydroxytriazoles were afforded using CDSCS.
CDSCS was demonstrated to be an efficient, thermally and chemi-
cally stable, environmental compatible and low cost catalyst that
can be easily prepared and reused for many consecutive runs
without a significant decrease in its catalytic reactivity.
b-azido alcohols and alkynes
b
4.3.1. 2-((1-(2-Hydroxy-3-(naphthalen-2-yloxy)propyl)-1H-1,2,3-
triazol-4-yl)methyl) isoindoline-1,3-dione (3a). Column chroma-
tography on silica gel (EtOAc/n-hexane, 4:1) afforded the prod-
uct as a pale-yellow solid; yield: 3.98 g (93%); mp 208.4 ꢀC; Rf
(EtOAc/n-hexane, 4:1)¼0.56; 1H NMR (250 MHz, DMSO-d6):
4. Experimental
4.1. General
d
¼4.03e4.05 (m, 2H, NCH2CH), 4.28 (s, 1H, OH, exchangeable
with D2O), 4.42 (dd, J¼7.5, 13.8 Hz, 1H, ArOCHAHB), 4.57 (dd,
J¼3.6, 13.8 Hz, 1H, ArOCHAHB), 4.84 (s, 2H, NCH2C]C), 5.61e5.64
(m, 1H, CHOH), 7.12e7.42 (m, 4H, aryl), 7.74e7.86 (m, 7H, aryl),
8.08 (s, 1H, C(5)eH, triazole); 13C NMR (62.5 MHz, DMSO-d6):
All preliminary chemicals were purchased from Fluka, Merck
and/or SigmaeAldrich. Preparation of SSA was achieved due to
procedure described in literature.31 Solvents were purified and
dried by standard procedures, and stored over 3 A molecular sieves.
Reactions were followed by TLC using SILG/UV 254 silica gel plates.
Column chromatography was performed on silica gel 60
ꢀ
d
¼32.8, 52.6, 67.7, 69.5, 106.7, 118.5, 123.1, 123.6, 124.2, 126.3,
126.6, 127.4, 128.5, 129.2, 131.5, 134.1, 134.4, 142.0, 156.1, 167.3; IR
(KBr): 3366, 3152, 3087, 3048, 2931, 1775, 1723, 1628, 1558,

M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
7819
1423 cmꢁ1; MS (EI) m/z (%): 428 (7.5) [Mþ]; Anal. Calcd for
C24H20N4O4: C, 67.28; H, 4.71; N, 13.08; found: C, 67.36; H, 4.63;
N, 13.19.
1431 cmꢁ1; MS (EI) m/z (%): 333 (11.7) [Mþ]; Anal. Calcd for
C14H19N7O3: C, 50.44; H, 5.75; N, 29.41; found: C, 50.49; H, 5.87; N,
29.54.
4.3.2. 2-((1-(2-Hydroxy-3-(4-methoxyphenoxy)-propyl)-1H-1,2,3-
triazol-4-yl)methyl) isoindoline-1,3-dione (3b). Column chroma-
tography on silica gel (EtOAc/n-hexane, 4:1) afforded the product as
a yellow solid; yield: 3.75 g (92%); mp 141.3 ꢀC; Rf (EtOAc/n-hexane,
4.3.6. 1-(4-((1H-Benzo[d]imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-
yl)-3-phenoxypropan-2-ol (3f). Column chromatography on silica
gel (EtOAc) afforded the product as a yellow foam; yield: 2.96 g
(85%); Rf (EtOAc)¼0.42; 1H NMR (250 MHz, DMSO-d6):
4:1)¼0.51; 1H NMR (250 MHz, DMSO-d6):
d¼3.64 (s, 3H, OCH3),
d
¼3.88e3.94 (m, 2H, NCH2CH), 4.16 (s, 1H, OH, exchangeable with
3.81e3.83 (m, 2H, NCH2CH), 4.17 (s, 1H, OH, exchangeable with
D2O), 4.33 (dd, J¼7.8, 13.8 Hz, 1H, ArOCHAHB), 4.50 (dd, J¼3.4,
13.8 Hz, 1H, ArOCHAHB), 4.83 (s, 2H, NCH2C]C), 5.50e5.52 (m, 1H,
CHOH), 6.81e6.85 (m, 4H, aryl), 7.80e7.82 (m, 4H, aryl), 8.03 (s, 1H,
D2O), 4.35e4.43 (m, 1H, CHOH), 4.55e4.61 (m, 2H, ArOCH2), 5.55 (s,
2H, NCH2C]C), 6.90 (d, J¼7.5 Hz, 2H, aryl), 7.14e7.53 (m, 5H, aryl),
7.62 (d, J¼7.5 Hz, 2H, aryl), 8.13 (s, 1H, C(5)eH, triazole), 8.31 (s, 1H,
C(2)eH, benzimidazole); 13C NMR (62.5 MHz, DMSO-d6):
d
¼50.2,
C(5)eH, triazole); 13C NMR (62.5 MHz, DMSO-d6):
d¼32.8, 52.7,
52.7, 67.7, 69.3, 110.7, 114.4, 119.4, 120.7, 128.9, 129.3, 129.4, 129.6,
133.5, 139.0, 142.2, 143.8, 158.2; IR (liquid film): 3296, 3050, 2966,
2929, 1669, 1591, 1492 cmꢁ1; MS (EI) m/z (%): 349 (8.5) [Mþ]; Anal.
Calcd for C19H19N5O2: C, 65.32; H, 5.48; N, 20.04; found: C, 65.37; H,
5.46; N, 20.10.
55.2, 67.8, 70.0, 114.5, 115.4, 123.1, 124.1, 131.5, 134.4, 142.0, 152.3,
153.4, 167.3; IR (KBr): 3326, 3145, 2990, 2971, 1764, 1709, 1506,
1427 cmꢁ1; MS (EI) m/z (%): 408 (3.9) [Mþ]; Anal. Calcd for
C21H20N4O5: C, 61.76; H, 4.94; N, 13.72; found: C, 61.70; H, 5.03; N,
13.76.
4.3.7. 1-((1-(3-Butoxy-2-hydroxypropyl)-1H-1,2,3-triazol-4-yl)
methyl)indoline-2,3-dione (3g). Column chromatography on silica
gel (EtOAc/n-hexane, 2:1) afforded the product as a scarlet foam;
yield: 3.26 g (91%); Rf (EtOAc/n-hexane, 4:1)¼0.45, 1H NMR
4.3.3. 7-((1-(2-Hydroxy-3-(4-methoxyphenoxy)-propyl)-1H-1,2,3-
triazol-4-yl)methyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione
(3c). Column chromatography on silica gel (EtOAc) afforded the
product as a white solid; yield: 3.66 g (83%); mp 183.1 ꢀC; Rf
(250 MHz, CDCl3):
d
¼0.53 (t, J¼7.2 Hz, 3H, CH3), 0.95e1.04 (m,
(EtOAc)¼0.21; 1H NMR (250 MHz, DMSO-d6):
d
¼3.16 (s, 3H,
2H, CH2CH3), 1.13e1.22 (m, 2H, OCH2CH2), 3.08e3.14 (m, 4H,
CH2OCH2), 3.49e3.51 (m, 1H, CHOH), 3.84 (s, 1H, OH, ex-
changeable with D2O), 4.02 (dd, J¼7.3, 14.0 Hz, 1H, NCHAHB),
4.20 (dd, J¼3.4, 14.0 Hz, 1H, NCHAHB), 4.65 (s, 2H, NCH2C]C),
6.72e6.91 (m, 2H, aryl), 7.18e7.26 (m, 2H, aryl), 7.58 (s, 1H,
N(3)eCH3), 3.35 (s, 3H, N(1)eCH3), 3.65 (s, 3H, OCH3), 3.80e3.83
(m, 2H, NCH2CH), 4.15 (s, 1H, OH, exchangeable with D2O), 4.35
(dd, J¼7.5, 13.8 Hz, 1H, ArOCHAHB), 4.51 (dd, J¼3.3, 13.8 Hz, 1H,
ArOCHAHB), 5.49e5.51 (m, 1H, CHOH), 5.54 (s, 2H, NCH2C]C),
6.75e6.83 (m, 4H, aryl), 8.07 (s, 1H, C(5)eH, triazole), 8.13 (s, 1H,
C(5)eH, triazole); 13C NMR (62.5 MHz, CDCl3):
d
¼13.8, 18.8, 31.5,
C(8)eH, theophylline); 13C NMR (62.5 MHz, DMSO-d6):
d
¼27.4,
35.3, 53.2, 69.0, 71.3, 71.6, 111.4, 117.4, 123.9, 124.6, 125.1, 138.5,
141.3, 150.2, 157.9, 183.1; IR (liquid film): 3419, 3035, 2950, 1739,
1614, 1585, 1471 cmꢁ1; MS (EI) m/z (%): 358 (5.9) [Mþ]; Anal.
Calcd for C18H22N4O4: C, 60.32; H, 6.19; N, 15.63; found: C, 60.47;
H, 6.13; N, 15.68.
29.3, 41.0, 52.7, 55.2, 67.7, 70.0, 105.7, 114.4, 115.3, 124.8, 142.0,
142.3, 148.2, 150.9, 152.2, 153.4, 154.3; IR (KBr): 3222, 3127, 2931,
1725, 1710, 1657, 1549, 1439 cmꢁ1; MS (EI) m/z (%): 441 (10.3)
[Mþ]; Anal. Calcd for C20H23N7O5: C, 54.42; H, 5.25; N, 22.21;
found: C, 54.31; H, 5.39; N, 22.27.
4.3.8. 1-((1-(3-(Allyloxy)-2-hydroxypropyl)-1H-1,2,3-triazol-4-yl)
methyl)indoline-2,3-dione (3h). Column chromatography on silica
gel (EtOAc/n-hexane, 2:1) afforded the product as a scarlet foam;
yield: 3.18 g (93%); Rf (EtOAc/n-hexane, 4:1)¼0.39; 1H NMR
4.3.4. 7-((1-(3-(4-Chloro-3-methylphenoxy)-2-hydroxypropyl)-1H-
1,2,3-triazol-4-yl)methyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione
(3d). Column chromatography on silica gel (EtOAc) afforded the
product as a white solid; yield: 3.67 g (80%); mp 117.0 ꢀC; Rf
(250 MHz, CDCl3):
d
¼3.18e3.22 (m, 2H, OCH2CHOH), 3.58e3.60
(EtOAc)¼0.28; 1H NMR (250 MHz, DMSO-d6):
d¼2.23 (s, 3H,
(m, 1H, CHOH), 3.73e3.76 (m, 2H, CH2CH]C), 3.96 (s, 1H, OH,
exchangeable with D2O), 4.13 (dd, J¼7.2, 14.0 Hz, 1H, NCHAHB),
4.29 (dd, J¼3.6, 14.0 Hz, 1H, NCHAHB), 4.75 (s, 2H, NCH2C]C),
4.89e5.04 (m, 2H, ]CH2), 5.53e5.67 (m, 1H, ]CH), 6.86e7.01
(m, 2H, aryl), 7.28e7.33 (m, 2H, aryl), 7.67 (s, 1H, C(5)eH, tri-
ArCH3), 3.37 (s, 6H, N(3)eCH3, N(1)eCH3), 3.80e3.86 (m, 2H,
NCH2CH), 4.17 (s, 1H, OH, exchangeable with D2O), 4.37e4.41 (m,
2H, ArOCH2), 4.50e4.57 (m, 1H, CHOH), 5.55 (s, 2H, NCH2C]C),
6.71 (s, 1H, aryl), 6.89 (d, J¼7.5 Hz, 1H, aryl), 7.22 (d, J¼7.5 Hz, 1H,
aryl), 8.07 (s, 1H, C(5)eH, triazole), 8.13 (s, 1H, C(8)eH, theophyl-
azole); 13C NMR (62.5 MHz, CDCl3):
d
¼35.3, 53.2, 69.0, 71.0, 72.3,
line); 13C NMR (62.5 MHz, DMSO-d6):
d
¼19.6, 27.4, 29.3, 41.0, 52.7,
111.4, 117.4, 117.5, 123.9, 124.6, 125.2, 134.1, 138.6, 141.3, 150.2,
158.0, 183.1; IR (liquid film): 3400, 3083, 2984, 1734, 1625, 1591,
1468 cmꢁ1; MS (EI) m/z (%): 342 (7.5) [Mþ]; Anal. Calcd for
C17H18N4O4: C, 59.64; H, 5.30; N, 16.37; found: C, 59.60; H, 5.21;
N, 16.46.
67.6, 69.6, 105.7, 113.5, 117.0, 124.8, 129.3, 133.0, 134.5, 136.4, 148.2,
149.3, 150.8, 154.3, 156.9; IR (KBr): 3050, 2964, 2925, 1721, 1705,
1663, 1596, 1498, 1021 cmꢁ1; MS (EI) m/z (%): 459 (6.3) [Mþ]; Anal.
Calcd for C20H22ClN7O4: C, 52.23; H, 4.82; Cl, 7.71; N, 21.32; found:
C, 52.16; H, 4.85; Cl, 7.78; N, 21.29.
4.3.9. 1-(4-((4-Chlorophenoxy)methyl)-1H-1,2,3-triazol-1-yl)-3-
(2,4-dichlorophenoxy)propan-2-ol (3i). Column chromatography
on silica gel (EtOAc/n-hexane, 2:1) afforded the product as
a pale-yellow solid; yield: 3.77 g (88%); mp 129.5 ꢀC; Rf (EtOAc/
n-hexane, 4:1)¼0.62; 1H NMR (250 MHz, DMSO-d6):
4.3.5. 7-((1-(2-Hydroxybutyl)-1H-1,2,3-triazol-4-yl)methyl)-1,3-
dimethyl-1H-purine-2,6(3H,7H)-dione (3e). Column chromatogra-
phy on silica gel (EtOAc) afforded the product as a white solid;
yield: 2.70 g (81%); mp 144.2 ꢀC; Rf (EtOAc)¼0.17; 1H NMR
(250 MHz, DMSO-d6):
d
¼0.82 (t, J¼7.2 Hz, 3H, CH2CH3), 1.13e1.38
d
¼3.97e4.08 (m, 2H, NCH2CH), 4.28 (s, 1H, OH, exchangeable
(m, 2H, CH2CH3), 3.16 (s, 3H, N(3)eCH3), 3.35 (s, 3H, N(1)eCH3),
3.68 (s, 1H, OH, exchangeable with D2O), 4.12 (dd, J¼7.6, 13.7 Hz,1H,
NCHAHB), 4.28 (dd, J¼3.2, 13.7 Hz, 1H, NCHAHB), 4.94e4.97 (m, 1H,
CHOH), 5.52 (s, 2H, NCH2C]C), 8.00 (s,1H, C(5)eH, triazole), 8.11 (s,
with D2O), 4.45 (dd, J¼7.5, 13.8 Hz, 1H, ArOCHAHB), 4.61 (dd,
J¼3.2, 13.8 Hz, 1H, ArOCHAHB), 5.13 (s, 2H, OCH2C]C), 5.66e5.68
(m, 1H, CHOH), 7.02e7.34 (m, 6H, aryl), 7.51 (s, 1H, aryl), 8.19 (s,
1H, C(5)eH, triazole); 13C NMR (62.5 MHz, DMSO-d6):
61.3, 67.6, 70.6, 115.2, 116.4, 122.5, 124.5, 124.7, 125.6, 128.0,
128.7, 129.1, 142.1, 152.8, 156.8; IR (KBr): 3264, 3028, 2921, 1647,
1590, 1491, 1036 cmꢁ1; MS (EI) m/z (%): 428 (2.6) [Mþ]; Anal.
d
¼52.5,
1H, C(8)eH, theophylline); 13C NMR (62.5 MHz, DMSO-d6):
27.0, 27.4, 29.3, 41.0, 55.0, 70.2, 105.7, 124.5, 141.9, 142.3, 148.2,
150.9, 154.3; IR (KBr): 3252, 3107, 2961, 1719, 1708, 1665, 1542,
d
¼9.6,

7820
M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
Calcd for C18H16Cl3N3O3: C, 50.43; H, 3.76; Cl, 24.81; N, 9.80;
found: C, 50.57; H, 3.81; Cl, 24.87; N, 9.71.
3.63e3.65 (m, 2H, NCH2CH), 3.95 (s, 1H, CHOH, exchangeable with
D2O), 4.09 (dd, J¼7.5, 13.7 Hz, 1H, ArOCHAHB), 4.25 (dd, J¼2.7,
13.4 Hz, 1H, ArOCHAHB), 4.88 (s, 1H, (CH3)2COH, exchangeable with
D2O), 5.29e5.31 (m, 1H, CHOH), 6.60 (d, J¼8.2 Hz, 2H, aryl),
6.86e7.04 (m, 7H, aryl), 7.61 (s, 1H, C(5)eH, triazole); 13C NMR
4.3.10. 1-(4-Benzylphenoxy)-3-(4-((4-chlorophenoxy)-methyl)-1H-
1,2,3-triazol-1-yl)propan-2-ol (3j). Column chromatography on sil-
ica gel (EtOAc/n-hexane, 2:1) afforded the product as a white solid;
yield: 3.86 g (86%); mp 110.1 ꢀC; Rf (EtOAc/n-hexane, 4:1)¼0.65; 1H
(62.5 MHz, DMSO-d6):
d
¼30.7, 40.4, 52.4, 67.0, 67.9, 69.5, 114.5,
121.6, 125.8, 128.3, 128.5, 129.7, 133.5, 141.6, 155.7, 156.6; IR (KBr):
3329, 3065, 2971, 1643, 1584, 1511, 1453 cmꢁ1; MS (EI) m/z (%): 367
(5.1) [Mþ]; Anal. Calcd for C21H25N3O3: C, 68.64; H, 6.86; N, 11.44;
found: C, 68.50; H, 6.81; N, 11.53.
NMR (250 MHz, DMSO-d6):
d
¼3.59 (s, 2H, PhCH2), 3.85e3.88 (m,
2H, NCH2CH), 4.10 (s, 1H, OH, exchangeable with D2O), 4.39 (dd,
J¼7.6, 13.8 Hz, 1H, ArOCHAHB), 4.56 (dd, J¼3.3, 13.8 Hz, 1H, ArO-
CHAHB), 5.13 (s, 2H, OCH2C]C), 5.57e5.59 (m, 1H, CHOH), 6.83 (d,
J¼8.3 Hz, 2H, aryl), 7.04e7.56 (complex, 11H, aryl), 8.18 (s, 1H, C(5)e
4.3.15. 1-(4-(2-Hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)-3-
phenoxypropan-2-ol (3o). Column chromatography on silica gel
(EtOAc/n-hexane, 2:1) afforded the product as a white solid; yield:
2.50 g (90%); mp 92.9 ꢀC; Rf (EtOAc/n-hexane, 4:1)¼0.35; 1H NMR
H, triazole); 13C NMR (62.5 MHz, DMSO-d6):
d¼40.4, 52.6, 61.3, 67.8,
69.5, 114.5,116.4,124.5,125.6, 125.8, 128.3,128.5, 129.2, 129.6,133.5,
141.6, 142.0, 156.6, 156.9; IR (KBr): 3262, 3029, 2912, 1604, 1575,
1492 cmꢁ1; MS (EI) m/z (%): 449 (3.2) [Mþ]; Anal. Calcd for
C25H24ClN3O3: C, 66.74; H, 5.38; Cl, 7.88; N, 9.34; found: C, 66.86; H,
5.34; Cl, 7.81; N, 9.45.
(250 MHz, DMSO-d6):
d
¼1.39 (s, 6H, 2CH3), 3.84e3.86 (m, 2H,
NCH2CH), 4.15 (s, 1H, CHOH, exchangeable with D2O), 4.29 (dd,
J¼7.3, 13.8 Hz, 1H, ArOCHAHB), 4.44 (dd, J¼3.8, 13.8 Hz, 1H, ArO-
CHAHB), 5.03 (s, 1H, (CH3)2COH, exchangeable with D2O), 5.48e5.50
(m, 1H, CHOH), 6.85e6.88 (m, 3H, aryl), 7.18e7.24 (m, 2H, aryl), 7.78
4.3.11. 2-(4-((4-Nitrophenoxy)methyl)-1H-1,2,3-triazol-1-yl)cyclo-
hexanol (3k). Column chromatography on silica gel (EtOAc/n-hex-
ane, 2:1) afforded the product as a brown solid; yield: 2.59 g (90%);
mp 143.6 ꢀC; Rf (EtOAc/n-hexane, 4:1)¼0.58; 1H NMR (250 MHz,
(s, 1H, C(5)eH, triazole); 13C NMR (62.5 MHz, DMSO-d6):
d
¼30.7,
52.4, 67.0, 67.9, 69.4, 114.5, 120.7, 121.4, 129.4, 155.5, 158.3; IR (KBr):
3316, 3100, 2970, 1597, 1588, 1468 cmꢁ1; MS (EI) m/z (%): 277 (1.3)
[Mþ]; Anal. Calcd for C14H19N3O3: C, 60.63; H, 6.91; N, 15.15; found:
C, 60.75; H, 6.83; N, 15.10.
CDCl3):
d
¼1.31e1.45 (m, 4H, 2CH2), 1.80e1.98 (m, 2H, CH2),
2.12e2.17 (m, 2H, CH2), 3.14 (s, 1H, OH, exchangeable with D2O),
3.97e4.10 (m, 1H, CHOH), 4.15e4.24 (m, 1H, NCH), 5.28 (s, 2H,
OCH2C]C), 7.07 (d, J¼7.8 Hz, 2H, aryl), 7.78 (s, 1H, C(5)eH, triazole),
Acknowledgements
8.11 (d, J¼7.8 Hz, 2H, aryl); 13C NMR (62.5 MHz, CDCl3):
¼23.9,
d
24.8, 31.7, 34.0, 62.4, 67.1, 72.6, 114.9, 123.2, 125.9, 141.9, 142.1, 163.1;
IR (KBr): 3390, 3035, 2957,1656,1585,1498, 1336 cmꢁ1; MS (EI) m/z
(%): 318 (3.2) [Mþ]; Anal. Calcd for C15H18N4O4: C, 56.60; H, 5.70; N,
17.60; found: C, 56.67; H, 5.62; N, 17.55.
We wish to thank Pars Industrial Pioneer Engineering Company
for financial support of this work. We are also grateful to Shiraz
University of Technology and Shiraz University Research Councils
for partial support of this work.
4.3.12. 1-Phenoxy-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-ol
(3l). Column chromatography on silica gel (EtOAc/n-hexane, 2:1)
afforded the product as a colorless solid; yield: 2.60 g (88%); mp
125.6 ꢀC; Rf (EtOAc/n-hexane, 4:1)¼0.63; 1H NMR (250 MHz,
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.07.032.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
CDCl3):
d
¼3.84 (s, 1H, OH, exchangeable with D2O), 4.03e4.09 (m,
2H, NCH2CH), 4.51 (dd, J¼3.6, 12.8 Hz, 2H, ArOCH2), 4.66e4.78 (m,
1H, CHOH), 6.92e7.04 (m, 3H, aryl), 7.60e7.64 (m, 5H, aryl),
7.69e7.73 (m, 2H, aryl), 7.87 (s, 1H, C(5)eH, triazole); 13C NMR
References and notes
(62.5 MHz, CDCl3):
d
¼53.6, 68.6, 68.9, 114.5, 121.5, 121.6, 125.5,
128.2, 128.8, 129.7, 130.1, 147.2, 158.3; IR (KBr): 3420, 3071, 2927,
1661, 1595, 1490, cmꢁ1; MS (EI) m/z (%): 295 (7.1) [Mþ]; Anal. Calcd
for C17H17N3O2: C, 69.14; H, 5.80; N, 14.23; found: C 69.05, H 5.91, N
14.15.
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4.3.13. 1-(Allyloxy)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-ol
(3m). Column chromatography on silica gel (EtOAc/n-hexane, 2:1)
afforded the product as a colorless solid; yield: 2.25 g (87%); mp
71.4 ꢀC; Rf (EtOAc/n-hexane, 4:1)¼0.61; 1H NMR (250 MHz, CDCl3):
d
¼3.14 (d, J¼5.1 Hz, CH2CH]C, 2H), 3.72e3.77 (m, 2H, OCH2CHOH),
3.95e4.13 (m, 2H, NCH2CH), 4.24e4.29 (m, 1H, CHOH), 4.56 (s, 1H,
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5.51e5.65 (m, 1H, ]CH), 6.93e7.09 (m, 3H, aryl), 7.32e7.38 (m, 2H,
aryl), 7.56 (s, 1H, C(5)eH, triazole); 13C NMR (62.5 MHz, DMSO-d6):
d
¼53.5, 69.0, 71.3, 72.3, 117.5, 121.0, 125.4, 128.1, 128.8, 129.7, 134.2,
147.1; IR (KBr): 3350, 3050, 2978,1591, 1455, 1357 cmꢁ1; MS (EI) m/z
(%): 259 (10.5) [Mþ]; Anal. Calcd for C14H17N3O2: C, 64.85; H, 6.61;
N, 16.20; found: C, 64.93; H, 6.69; N, 16.14.
4.3.14. 1-(4-Benzylphenoxy)-3-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-
triazol-1-yl)propan-2-ol (3n). Column chromatography on silica gel
(EtOAc/n-hexane, 2:1) afforded the product as a white solid; yield:
3.34 g (91%); mp 86.5 ꢀC; Rf (EtOAc/n-hexane, 4:1)¼0.36; 1H NMR
(250 MHz, DMSO-d6):
d
¼1.22 (s, 6H, 2CH3), 3.18 (s, 2H, PhCH2),

M.N. Soltani Rad et al. / Tetrahedron 68 (2012) 7812e7821
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