1,4-Dihydroxyanthraquinone-copper(II) nanoparticles immobilized on silica gel: A highly efficient, copper scavenger and recyclable heterogeneous nanocatalyst for a click approach to the three-component synthesis of 1,2,3-triazole derivatives in water

Article abstract of DOI:10.1007/s13738-011-0046-3

High yielding preparation of structurally different β-hydroxy 1,4-disubstituted 1,2,3-triazole from the regio-selective reaction of epoxides 2a-2c with wide range of terminal alkynes 1a-1j, and sodium azide in the presence of catalytic amount, complexed form of homogeneous catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II)] (5.0 mol%), [AQ ₂Cu(II)] 7 at 25 °C in water has been described. To benefit from the recovery and reuse of the catalyst, a novel heterogeneous nanoparticles of catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II) aminopropyl silica gel] (5.0 mol%), [AQ₂Cu(II)-APSiO₂] 13 bearing oxygen anthraquinone ligands with strong copper(II) affinity was easily prepared by using silica gel as a suitable support. The heterogeneous catalyst was fully characterized by XRD, SEM, AFM, ICP, TG methods for analysis of nitrogen adsorption, and FT-IR techniques. The remarkable features of this protocol are high yields, short reaction times, a cleaner reaction profile in an environmentally benign solvent (H₂O), one-pot procedure and the method is applicable to large-scale operation without any problem. Furthermore, the catalyst could be recovered and easily removed by simple filtration of the reaction mixture and it was recycled ten times showing negligible copper leaching. In their uncomplexed form of homogeneous catalyst [AQ ₂Cu(II)] 7 and heterogeneous catalyst [AQ₂Cu(II)- APSiO₂] 13, the anthraquinone ligand 6 and [AQ-APSiO₂] 12 are very efficient copper scavengers able to catalyze the 1,3-dipolar cycloaddition reaction of azides with alkynes (CuAAC) without pre-synthesis of catalysts.

Full text of DOI:10.1007/s13738-011-0046-3

J IRAN CHEM SOC (2012) 9:231–250
DOI 10.1007/s13738-011-0046-3
ORIGINAL PAPER
1,4-Dihydroxyanthraquinone-copper(II) nanoparticles
immobilized on silica gel: a highly efficient, copper scavenger
and recyclable heterogeneous nanocatalyst for a click approach
to the three-component synthesis of 1,2,3-triazole derivatives
in water
•
Hashem Sharghi Abbas Khoshnood
•
•
Mohammad Mahdi Doroodmand Reza Khalifeh
Received: 24 July 2011 / Accepted: 10 October 2011 / Published online: 13 January 2012
Ó Iranian Chemical Society 2012
Abstract High yielding preparation of structurally dif-
ferent b-hydroxy 1,4-disubstituted 1,2,3-triazole from the
regio-selective reaction of epoxides 2a–2c with wide range
of terminal alkynes 1a–1j, and sodium azide in the pres-
ence of catalytic amount, complexed form of homogeneous
catalyst [bis 1,4-mono ester hydroxy anthraquinone cop-
per(II)] (5.0 mol%), [AQ2Cu(II)] 7 at 25 °C in water has
been described. To benefit from the recovery and reuse of
the catalyst, a novel heterogeneous nanoparticles of cata-
lyst [bis 1,4-mono ester hydroxy anthraquinone copper(II)
aminopropyl silica gel] (5.0 mol%), [AQ2Cu(II)-APSiO2]
13 bearing oxygen anthraquinone ligands with strong
copper(II) affinity was easily prepared by using silica gel as
a suitable support. The heterogeneous catalyst was fully
characterized by XRD, SEM, AFM, ICP, TG methods for
analysis of nitrogen adsorption, and FT-IR techniques. The
remarkable features of this protocol are high yields, short
reaction times, a cleaner reaction profile in an environ-
mentally benign solvent (H2O), one-pot procedure and the
method is applicable to large-scale operation without any
problem. Furthermore, the catalyst could be recovered and
easily removed by simple filtration of the reaction mixture
and it was recycled ten times showing negligible copper
leaching. In their uncomplexed form of homogeneous
catalyst [AQ2Cu(II)]
7
and heterogeneous catalyst
[AQ2Cu(II)-APSiO2] 13, the anthraquinone ligand 6 and
[AQ-APSiO2] 12 are very efficient copper scavengers able
to catalyze the 1,3-dipolar cycloaddition reaction of azides
with alkynes (CuAAC) without pre-synthesis of catalysts.
Keywords Anthraquinone ꢀ Heterogeneous nanocatalyst ꢀ
Triazole ꢀ Click chemistry ꢀ Water
Introduction
1,2,3-Triazoles are important blocks of five-membered
nitrogen aromatic heterocyclic compounds. These biolog-
ical heterocyclic molecules with high chemical stability to
oxidation, reduction and hydrolysis have found wide
application in the pharmaceuticals organic synthesis [1–3],
drug discovery [4–7], anti-HIV therapy [8, 9], fluorescence
chemosensors [10], etc. [11–17]. Synthesis of 1,2,3-tria-
zoles through thermal cycloaddition [18–20] of azide-
alkynes usually requires prolonged heating and results in
mixtures of both 1,4- and 1,5-regio-isomers (Scheme 1).
The copper(I)-catalyzed reaction (CuAAC) [21–34], one of
the most reliable click reactions [35–44] was reported by
the groups of Fokin, Sharpless [45, 46] and Meldal [47]. It
transforms terminal alkynes and organic azides exclusively
into the corresponding 1,4-disubstituted 1,2,3-triazoles.
Among the three most common oxidation states of
copper (0, 1?, 2?), the (1?) state is the least thermody-
namically stable and can disproportionate to a mixture
of Cu(II) and Cu(0) or can be oxidized to catalytically
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-011-0046-3) contains supplementary
material, which is available to authorized users.
H. Sharghi (&) ꢀ A. Khoshnood ꢀ M. M. Doroodmand
Department of Chemistry, College of Sciences,
Shiraz University, 71454 Shiraz, Iran
e-mail: shashem@chem.susc.ac.ir
M. M. Doroodmand
Nanotechnology Research Institute,
Shiraz University, Shiraz, Iran
R. Khalifeh
Department of Chemistry, Shiraz University of Technology,
71555-313 Shiraz, Iran
123

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J IRAN CHEM SOC (2012) 9:231–250
Scheme 1 Synthesis of 1,2,3-
triazol via a thermal b copper
catalytic cycloaddition
N
N
N
N
1,4-disubstituted-1,2,3-triazole
1,5-disubstituted-1,2,3-triazole
+
N
N
R1
R1
R2
a
R2
R1-N3
R2
+
N
N
N
(CuAAC)
b
1
1,4-disubstituted-1,2,3-triazol
R1
R2
inactive Cu(II) species [48, 49]. Therefore, under the
reported conditions at least two general method conditions:
(1) combination of copper(II) and a reducing agents like
ascorbate [45, 46, 48, 49] or t-BuOH [50] and (2) cop-
per(II)–ligand complex [51] have been accepted as the
suitable processes of choice for generating the required
copper(I) to complete the catalytic cycle of the (AAC)
reaction.
20 kV). Spectroscopic methods including X-ray diffraction
(XRD, D8, Advance, Bruker, AXS) and FT-IR spectrometry
(Shimadzu FT-IR 8300 spectrophotometer) were obtained
for characterization of the heterogeneous catalyst. Cyclic
Voltametry was performed by Metrohm 693 VA Processor.
Metal contents were obtained by ICP analyzer (Varian, vista-
pro). The TG analysis of the samples was analyzed using a
lab-made TG analyzer instrument. Mass spectra were
determined on a Shimadzu GCMS-QP 1000 EX instruments
at 70 or 20 eV. UV/vis. Spectra was obtained with an Ul-
trospec 3000 UV/Visible spectrometer. Melting points
determined in open capillary tubes in aBuchi-535 circulating
oil melting point apparatus. Elemental analyses were per-
formed by Thermo Finnigan CHNS-O analyzer, 1112 series.
The purity determination of the substrates and reaction
monitoring were accomplished by TLC on silica gel Poly-
Gram SILG/UV254 plates or by a Shimadzu Gas Chro-
matograph (GC-10A) instrument with a flame-ionization
detector using a column of 15% carbowax 20 M chromo-
sorb-w acid washed 60–80 mesh. Column chromatography
was carried out on short columns of silica gel 60 (70–230
mesh) in glass columns. Chemical materials were either
prepared in our laboratories or were purchased from Aldrich,
Fluka and Merck Companies.
Major problems associated with the recovery of homo-
geneous catalysts and the difficulties associated with the
recycling of the copper species have been improved by
covalent and non-covalent impregnation of copper species
onto a variety of supports such as nanoclusters [52], silica
gel [53, 54], zeolites [55–58], titanium oxide [59], alumina
[60, 61], Amberlyst [62], activated charcoal [63–65], etc.
[66–69].
The 1,4-dihydroxyanthraquinone, ‘‘quinizarin’’ [70]
system is an important chemical attribute of all anthracy-
clines. The capability of anthracyclines [71] and anthra-
quinones [72–79], to produce complex metal ions has been
recognized for a long time and has been well documented.
In the continuation of our studies to utilize a heteroge-
neous catalyst, for the synthesis of heterocyclic molecules of
biological interest and our ongoing green organic chemistry
program that uses water as a reaction medium [80–95], we
wish herein to report full details of the utilization of homo-
geneous [AQ2Cu(II)] 7 and also heterogeneous nanoparti-
cles of [AQ2Cu(II)-APSiO2] 13 as a novel, convenient,
stable and reused catalyst for the efficient conversion of non-
activated terminal alkynes to b-hydroxytriazoles (HIV-1
protease inhibitors) [96], by a three-component click reac-
tion at room temperature under aqueous condition.
Preparation of (4-hydroxy-9,10-dioxo-9,10-dihydro-
anthracen-1-yloxy)-acetic acid ethyl ester (6)
In a 50-mL flask were added 1,4-dihydroxyanthraquinone
(5) (1.0 mmol, 0.24 g), t-BuOK (0.5 mmol, 0.05 g), ethyl
2-bromoacetate (0.5 mmol, 0.11 mL), and DMF (25 mL).
The mixture was stirred at room temperature for 24 h. The
reaction mixture was poured into cooled water, the mixture
was filtered, and the residue was dried. The product 6
(yield, 86%) was isolated as red powder by column chro-
matography on silica gel: mp 153 °C; Rf 0.65 (50%
n-hexane:50% EtOAc); IR (KBr): m = 580 (w), 729 (m),
785 (m), 1,022 (m), 1,051 (m), 1,103 (m), 1,164 (m), 1,205
(s), 1,353 (m), 1,425 (m), 1,593 (m), 1,637 (m), 1,666 (m),
Experimental
General
NMR spectra were recorded on a Bruker Avance DPX-250
(1H NMR 250 MHz and 13C NMR 62.9 MHz) in pure
deuterated solvents with tetramethylsilane (TMS) as
internal standards. An atomic forced microscopy (AFM,
DME-SPM, version 2.0.0.9) was also used for AFM ima-
ges. Scanning electron micrographs were obtained by SEM
instrumentation (SEM, XL-30 FEG SEM, Philips, at
1
1,733 (s), 2,991 (w), 3,450 (br) cm-1; H NMR (CDCl3,
250 MHz): d = 1.24 (t, 3H, J = 7.1 Hz), 4.15–4.26 (m,
2H), 4.71 (s, 2H), 7.16 (d, 1H, J = 9.3 Hz), 7.30 (d, 1H,
J = 9.3 Hz), 7.65–7.70 (m, 2H), 8.13–8.16 (m, 2H), 12.91
(s, 1H); 13C NMR (CDCl3, 62.9 MHz): d = 14.2, 61.4,
68.1, 115.8, 121.2, 126.0, 126.4, 127.3, 128.3, 132.1,
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233
133.5, 134.7, 134.8, 152.2, 158.8, 168.7, 181.3, 188.6; MS:
m/z (%) = 328 (M? ?2, 0.5), 327 (M? ?1, 4.0), 326 (M?,
7.4), 297 (3.2), 280 (6.1), 253 (59.5), 224 (43.0), 183
(12.8), 167 (18.0), 149 (36.7), 113 (16.6), 83 (41.0), 57
(100.0); anal. calcd. for C18H14O6 (326.30): C 66.26, H
4.32%; found: C 66.03, H 4.51%.
followed by treatment with concentrated nitric acid (2 mL)
to digest the metal complex. The mixture was then trans-
ferred to a volumetric flask (100 mL), diluted 1:50 for the
second time and was determined by the ICP analysis. The
copper concentration was determined by measuring the
atomic emission (324.754 nm) with reference to a linear
(R = 0.99) calibration curve of (1–4 ppm) [AQ2Cu(II)-
APSiO2] 13 prepared in a manner identical to the sample
preparation.
Preparation of bis 1,4-mono ester hydroxy
anthraquinone metal complex (7–11)
Preparation of 1-hydroxyanthracene-9,10-dione
In a 50-mL flask were added (4-hydroxy-9,10-dioxo-9,10-
dihydro-anthracen-1-yloxy)-acetic acid ethyl ester (6)
(1.0 mmol, 0.33 g), metal chloride or acetate (0.5 mmol),
and MeOH (25 mL). The mixture was stirred at room
temperature for 5 h. After the completion of the reaction as
monitored by UV/vis., the solvent was evaporated. The
homogeneous metal complex [AQ2M(II)] 7–11 was iso-
lated as a dark red powder.
Dissolve (5.0 mmol) of 1-aminoanthraquinone in a mixture
of 20 mL of concentrated HCl and 20 mL of water con-
tained in a 500 mL round-bottomed flask. Place a ther-
mometer in the solution and immerse the flask in a bath of
crushed ice, cool until the temperature of the stirred solu-
tion falls below 5 °C. Dissolve (10 mmol) of sodium nitrite
in 50 mL of water and chill the solution by immersion in
the ice bath; add the sodium nitrite solution in small vol-
umes to the cold mixture, and keep the later well shaken.
After the addition is completed, stirring at 5 °C is contin-
ued for 1 h to complete the reaction. After that the solu-
tions are boiled for 1 h. They are then allowed to cool to
room temperature. The mixture was filtered under vacuum
and the residue was dried. The crude product was purified
by column chromatography on silica gel. 1-hydroxy
anthraquinone was isolated as yellow powder; yield: 93%;
mp 193–194 °C. Rf 0.16 (n-hexane). IR (KBr): m = 704 (s),
769 (s), 1,157 (w), 1,224 (w), 1,288 (s), 1,357 (s), 1,456 (s),
Anchoring of (4-hydroxy-9,10-dioxo-9,10-dihydro-
anthracen-1-yloxy)-acetic acid ethyl ester (6)
on aminopropyl silica gel (APSiO2) (12)
In a 50-mL flask were added (4-Hydroxy-9,10-dioxo-9,10-
dihydro-anthracen-1-yloxy)-acetic acid ethyl ester (6)
(2 mmol, 0.65 g), aminopropyl silica gel (15–35 lm; pore
size *9 nm) (0.9 mmol, 1.0 g), and absolute EtOH
(30 mL). The mixture was stirred under reflux for 72 h.
The reaction mixture was centrifuged and in order to
remove any physisorbed ligand, the resulting heteroge-
neous catalyst was centrifuged several times with ethanol
and acetone. The heterogeneous ligand [AQ-APSiO2] 12
was isolated as a pale brown powder.
1
1,587 (s), 1,635 (s), 1,672 (m) cm-1; H NMR (CDCl3,
250 MHz): d = 7.25 (dd, 1H, J1 = 8.4 Hz, J2 = 1.1 Hz),
7.63 (t, 1H, J = 8.3 Hz), 7.75–7.80 (m, 3H), 8.18–8.26 (m,
2H), 12.53 (s, 1H). 13C NMR (CDCl3, 62.9 MHz):
d = 116.0, 119.5, 124.3, 126.8, 127.3, 133.1, 133.3, 133.5,
134.1, 134.6, 136.7, 162.5, 182.2, 188.5; MS: m/z (%) =
226 (M? ?2, 1.1), 225 (M? ?1, 25.2), 224 (M?, 100.0),
196 (24.8), 168 (44.7), 139 (53.4), 113 (14.5), 84 (18.3), 57
(32.8); anal. calcd. for C14H8O3 (224.21): C 75.00, H
3.60%; found: C 75.12, H 3.80%.
Preparation of bis 1,4-mono ester hydroxy
anthraquinone copper(II) aminopropyl silica gel
[AQ2Cu(II)-APSiO2] (13)
In a 50-mL flask were added [AQ-APSiO2] 12 (1.0 g),
Cu(OAc)2.H2O (1 mmol), and MeOH (30 mL). The mix-
ture was stirred at room temperature for 24 h. The reaction
mixture was centrifuged and in order to remove any
physisorbed copper, the resulting heterogeneous catalyst
was centrifuged several times with methanol and water.
The heterogeneous copper catalyst [AQ2Cu(II)-APSiO2] 13
was isolated as a pale blue powder.
General procedure for the synthesis of alkynes
derivatives
A mixture of 1-hydroxy anthraquinone, 1,4-dihydroxyan-
thraquinone, 1,8-dihydroxyanthraquinone [114], theophyl-
line [115], theobromine [116] or sodium saccharine [117]
(5.0 mmol), propargyl bromide and K2CO3 in appropriate
concentration in DMF (50 mL) was stirred at room tem-
perature for 24 h and then poured into ice/water (500 mL).
The mixture was filtered under vacuum and the residue was
dried. The crude product was purified by column chroma-
tography on silica gel.
Determination of the copper content in catalyst
[AQ2Cu(II)-APSiO2] (13)
The [AQ2Cu(II)-APSiO2] 13 (100 mg) was extracted with
concentrated HCl (5 9 2 mL) in a screw-capped vessel,
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1-(Prop-2-ynyloxy)anthracene-9,10-dione (1b)
General procedure for the synthesis of 1,2,3-triazole
derivatives in the presence of a catalytic amount
of [(AQ)2Cu(II)-APSiO2] 13 and recycling
of the heterogeneous catalyst
Isolated as yellow powder; yield: 92%; mp 219–220 °C; Rf
0.6 (50% n-hexane:50%EtOAc). IR (KBr): m = 704 (s),
731 (m), 926 (m), 974 (s), 1,064 (s), 1,233 (s), 1,269 (s),
1,317 (s), 1,440 (m), 1,581 (s), 1,674 (s), 2,113 (w), 2,923
The heterogeneous catalyst [AQ2Cu(II)-APSiO2] 13 was
subjected to 10 successive reuses under the reaction con-
ditions: for each reaction, epoxide (1 mmol), alkyne
(1.1 mmol) and sodium azide (1.1 mmol) were mixed and
stirred in water (5 mL) in the presence of the catalytic
amount (5.0 mol%, 0.05 g) of [AQ2Cu(II)-APSiO2] 13 at
room temperature in an uncapped vial. According to the
ICP analysis, the copper content in the heterogeneous
catalyst was determined to be 5.82% (W/W). Therefore,
each gram of heterogeneous catalyst includes 9.15 9 10-4
mmol of copper. For 1.0 mmol of epoxides, 0.05 mmol of
heterogeneous catalyst is needed, which is equal to 0.055 g
of the heterogeneous catalyst. After the completion of the
reaction (Table 3) as monitored by TLC, the mixture was
diluted by H2O (10 mL), then the whole reaction mixture
was centrifuged and the supernatant was decanted to sep-
arate the heterogeneous catalyst, which was washed several
times with ethanol. The reaction vessel containing the
heterogeneous catalyst was recharged with epoxide,
alkyne, sodium azide and water for another reaction run.
The combined supernatant and organic washings were
extracted with EtOAc (3 9 10 mL), the combined organic
layer was washed with saturated brine and dried over
anhydrous Na2SO4. Removal of the solvent, followed by
purification on silica gel afforded the pure b-hydroxy 1,4-
disubstituted 1,2,3-triazole derivatives.
(w), 3,084 (w), 3,235 (s) cm-1
;
1H NMR (CDCl3,
250 MHz): d = 2.57 (t, 1H, J = 2.5 Hz), 5.95 (s, 2H),
7.51 (dd, 1H, J1 = 8.4 Hz, J2 = 1.1 Hz), 7.71–7.79 (m,
3H), 8.04 (dd, 1H, J1 = 7.7 Hz, J2 = 1.1 Hz), 8.22–8.29
(m, 2H); 13C NMR (DMSO-d6, 62.9 MHz): d = 56.5,
78.6, 79.0, 119.7, 120.6, 121.3, 126.0, 126.5, 131.8, 133.5,
134.4, 134.5, 135.0, 135.1, 157.6, 181.0,182.5; MS:
m/z (%) = 264 (M? ?2, 2.9), 263 (M? ?1, 20.7), 262
(M?, 55.7), 224 (100.0), 196 (30.7), 180 (44.3), 139 (91.4),
113 (21.4), 97 (45.0), 81 (38.6), 55 (80.0); anal. calcd. for
C17H10O3 (262.25): C 77.85, H 3.84%; found: C 77.66, H
3.97%.
1,4-Bis(prop-2-ynyloxy)anthracene-9,10-dione (1d)
Isolated as yellow powder; yield: 96%; mp 184–185 °C; Rf
0.86 (EtOAc); IR (KBr): m = 578 (m), 644 (s), 704 (s), 802
(s), 916 (s), 979 (s), 1,037 (s), 1,230 (s), 1,270 (s), 1,317
(s), 1,402 (m), 1,458 (s), 1,566 (s), 1,668 (s), 2,114 (w),
1
2,989 (w), 3,284 (s) cm-1; H NMR (250 MHz, CDCl3, d
ppm) 2.57 (t, 2H, J = 2.4 Hz), 4.88 (d, 4H, J = 2.4 Hz),
7.51 (s, 2H), 7.69–7.73 (m, 2H), 8.13–8.17 (m, 2H); 13C
NMR (CDCl3, 62.9 MHz): d = 58.2, 76.7, 78.1, 123.6,
124.6, 126.5, 133.5, 134.0, 152.8, 182.9; MS: m/z
(%) = 318 (M? ?2, 1.0), 317 (M? ?1, 4.4), 316 (M?,
5.2), 277 (38.0), 249 (21.0), 221 (21.4), 193 (12.6), 165
(32.2), 126 (19.9), 97 (47.7), 57 (100.0); anal. calcd. for
C20H12O4 (316.30): C 75.94, H 3.82%; found: C, 75.71, H
3.78%.
Spectral data of compounds 3a, 3b, 3c, 3g, 3v, 3w, and
3x could be found in our previous reports [51].
1-((1-(2-Hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-
yl)methoxy)anthracene-9,10-dione (3d)
Isolated as yellow powder; mp 183–184 °C; Rf 0.66
(EtOAc). IR (KBr): m = 708 (s), 947 (m), 1,054 (m), 1,271
(s), 1,316 (m), 1,456 (m), 1,581 (s), 1,664 (s), 3,447
General procedure for the synthesis of 1,2,3-triazole
derivatives in the presence of a catalytic amount
of [AQ2Cu(II)] 7
1
(s) cm-1; H NMR (DMSO-d6, 250 MHz): d = 3.99–4.08
(m, 1H), 4.29–4.35 (m, 1H), 5.29 (s, 2H), 5.48 (t, 1H,
J = 5.1 Hz), 5.85 (dd, 1H, J1 = 8.7 Hz, J2 = 4.7 Hz),
7.26–7.34 (m, 5H), 7.61–7.75 (m, 5H), 7.93 (d, 2H,
J = 7.1 Hz), 8.45 (s, 1H); 13C NMR (DMSO-d6,
62.9 MHz): d = 62.5, 63.1, 66.2, 119.4, 120.4, 120.8,
124.4, 125.9, 126.4, 127.1, 128.3, 128.6, 131.6, 133.3,
134.1, 134.4, 134.7, 135.1, 137.1, 142.2, 158.4, 180.8,
182.4; MS: m/z (%) = 427 (M? ?2, 2.8), 426 (M? ?1,
6.8), 425 (M?, 7.0), 261 (5.4), 224 (100), 196 (21.5), 168
(32.2), 139 (42.3), 121 (24.2), 91 (52.4), 55 (71.5); anal.
calcd. for C25H19N3O4 (425.43): C 70.58, H 4.50, N
9.88%; found: C 70.78, H 4.76, N 10.13%.
For each reaction, epoxide (1.0 mmol), alkyne (1.1 mmol)
and sodium azide (1.1 mmol) were mixed and stirred in
water (5 mL) in the presence of the catalytic amount
[AQ2Cu(II)] 7 (5.0 mol %) at room temperature. After the
completion of the reaction (Table 3) as monitored by TLC,
the solvent was evaporated and the product was extracted
with EtOAc (3 9 10 mL), the combined organic layer was
washed with saturated brine and dried over anhydrous
Na2SO4. Removal of the solvent to give the crude product,
followed by purification on silica gel afforded the pure
b-hydroxy 1,4-disubstituted 1,2,3-triazole derivatives.
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235
1-((1-(2-Hydroxy-3-phenoxypropyl)-1H-1,2,3-triazol-4-
yl)methoxy)anthracene-9,10-dione (3e)
114.3, 118.7, 120.6, 120.7, 123.5, 125.8, 129.4, 133.8,
134.0, 142.1, 157.3, 158.1, 181.0, 182.9; anal. calcd. for
C38H34N6O8 (702.71): C 64.95, H 4.88, N 11.96%; found:
C 64.82, H 5.00, N 11.73%.
Isolated as yellow powder; mp 148–149 °C; Rf 0.6
(EtOAc); IR (KBr): m = 707 (m), 752 (m), 948 (s), 1,053
(s), 1,263 (s), 1,321 (s), 1,456 (m), 1,496 (m), 1,585 (s),
1,664 (s), 2,950 (w), 3,139 (w), 3,463 (br) cm-1; 1H NMR
(CDCl3, 250 MHz): d = 3.90 (d, 2H, J = 5.2 Hz), 4.19–
4.26 (m, 1H), 4.48 (dd, 1H, J1 = 13.9 Hz, J2 = 7.4 Hz),
4.60 (dd, 1H, J1 = 13.9 Hz, J2 = 3.9 Hz), 5.29 (s, 2H),
5.72 (s, 1H), 6.89 (d, 2H, J = 7.1 Hz), 7.23 (t, 2H,
J = 7.9 Hz), 7.63–7.80 (m, 6H), 7.94–7.99 (m, 2H), 8.22
(s, 1H); 13C NMR (DMSO-d6, 62.9 MHz): d = 52.7, 62.7,
67.9, 69.3, 114.4, 119.2, 120.1, 120,6, 120.7, 125.5, 125.8,
126.4, 129.4, 131.5, 133.2, 134.1, 134.2, 134.6, 135.0,
142.4, 158.2, 158.4, 180.6, 182.3; MS: m/z (%) = 457 (M?
?2, 6.5), 456 (M? ?1, 17.5), 455 (M?, 22.9), 224 (64.9),
204 (30.3), 168 (23.5), 139 (43.8), 119 (26.8), 96 (54.9), 67
(100.0); anal. calcd. for C26H21N3O5 (455.46): C 68.56, H
4.65, N 9.23%; found: C 68.63, H 4.51, N 9.34%.
1,8-Bis((1-(2-hydroxycyclohexyl)-1H-1,2,3-triazol-4-
yl)methoxy)anthracene-9,10-dione (3i)
Isolated as yellow powder; mp 193 °C; Rf 0.8 (EtOAc); IR
(KBr): m = 746 (s), 804 (m), 975 (s), 1,053 (s), 1,132 (w),
1,232 (s), 1,276 (s), 13,223 (s), 1,448 (s), 1,583 (s), 1,664
(s), 2,862 (m), 2,937 (s), 3,097 (w), 3,143 (w), 3,429 (br)
cm-1; 1H NMR (DMSO-d6, 250 MHz): d = 1.13–1.16 (m,
6H), 1.33–1.96 (m, 10H), 3.70–3.74 (m, 2H), 4.18–4.25
(m, 2H), 4.96 (s, 1H), 4.99 (s, 1H), 5.32 (s, 4H), 7.66–7.84
(m, 6H), 8.23 (s, 2H); 13C NMR (DMSO-d6, 62.9 MHz):
d = 23.7, 24.3, 31.8, 34.7, 62.5, 65.8, 71.2, 118.6, 120.7,
123.7, 124.2, 134.0, 141.4, 157.5, 180.9, 182.9. MS:
m/z (%) = 600 (M? ?2, 0.8), 599 (M? ?1, 3.3), 598 (M?,
4.3), 502 (10.0), 420 (13.9), 240 (71.4), 152 (100.0), 81
(99.1); anal. calcd. for C32H34N6O6 (598.64): C 64.20, H
5.72, N 14.04%; found: C 64.35, H 5.94, N 14.31%.
1-((1-(2-Hydroxycyclohexyl)-1H-1,2,3-triazol-4-
yl)methoxy)anthracene-9,10-dione (3f)
1,4-Bis((1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-
yl)methoxy)anthracene-9,10-dione (3j)
Isolated as yellow powder; mp 173–174 °C; Rf 0.5
(EtOAc); IR (KBr): m = 574 (m), 659 (m), 705 (s), 804
(m), 869 (m), 970 (s), 1,068 (, 1,267 (s), 1,323 (s), 1,444
(s), 1,581 (s), 1,666 (s), 2,948 (w), 3,066 (w), 3,458 (br)
cm-1; 1H NMR (DMSO-d6, 250 MHz): d = 1.11–1.13 (m,
3H), 1.69–1.89 (m, 5H), 3.73–3.77 (m, 1H), 4.20–4.30 (m,
1H), 5.03 (s, 1H), 5.32 (s, 2H), 7.71–7.85 (m, 5H),
8.01–8.04 (m, 2H), 8.25 (s, 1H); 13C NMR (DMSO-d6,
62.9 MHz): d = 23.8, 24.4, 31.8, 34.8, 62.8, 65.9, 71.4,
119.1, 120.1, 120.6, 123.9, 125.8, 126.3, 131.4, 133.1,
134.0, 134.2, 134.6, 134.9, 141.7, 158.4, 180.5, 182.2; MS:
m/z (%) = 405 (M? ?2, 3.9), 404 (M? ?1, 11.7), 403
(M?, 14.0), 224 (95.6), 196 (14.7), 168 (23.0), 152 (100.0),
99 (22.8), 81 (92.7), 55 (65.0); anal. calcd. for C23H21N3O4
(403.43): C 68.47, H 5.25, N 10.42%; found: C 68.29, H
5.89, N 10.62%.
Isolated as yellow powder; mp 177–178 °C; Rf 0.1
(EtOAc); IR (KBr): m = 704 (m), 823 (w), 977 (m), 1,049
(s), 1,249 (s), 1,332 (m), 1,402 (w), 1,454 (w), 1,562 (m),
1,587 (m), 1,660 (s), 2,931 (w), 3,066 (w), 3,409 (br) cm-1
;
1H NMR (CDCl3, 250 MHz): d = 3.55 (s, 2H), 4.22 (dd,
2H, J1 = 12.5 Hz, J2 = 3.8 Hz), 4.64 (dd, 2H, J1 =
12.3 Hz, J2 = 8.5 Hz), 5.23 (s, 4H), 5.72 (dd, 2H,
J1 = 8.6, J2 = 3.8), 7.26–7.38 (m, 12H), 7.64–7.68 (m,
2H), 7.96 (s, 2H), 8.00–8.06 (m, 2H); 13C NMR (DMSO-
d6, 62.9 MHz): d = 63.1, 63.4, 66.1, 122.8, 123.6, 124.4,
125.8, 127.1, 128.2, 128.6, 133.5, 133.6, 137.3, 142.5,
152.6, 181.9; MS: m/z (%) = 642 (M?, 0.7), 442 (0.7), 303
(1.0), 256 (1.4), 149 (18.0), 97 (48.7), 57 (100.0); anal.
calcd. for C36H30N6O6 (642.66): C 67.28, H 4.71, N
13.08%; found: C 67.11, H 4.90, N 13.24%.
1,8-Bis((1-(2-hydroxy-3-phenoxypropyl)-1H-1,2,3-triazol-
4-yl)methoxy)anthracene-9,10-dione (3h)
1,4-Bis((1-(2-hydroxy-3-phenoxypropyl)-1H-1,2,3-triazol-
4-yl)methoxy)anthracene-9,10-dione (3k)
Isolated as yellow powder; mp 153–154 °C; Rf 0.35
(EtOAc); IR (KBr): m = 750 (s), 792 (w), 817 (w), 842 (w),
968 (m), 1,045 (s), 1,130 (w), 1,240 (s), 1,278 (s), 1,317 (s),
1,460 (s), 1,494 (s), 1,587 (s), 1,668 (s), 2,927(w), 3,080
Isolated as yellow powder; mp 153–154 °C; Rf 0.16
(EtOAc); IR (KBr): m = 582 (w), 692 (w), 756 (m), 817
(m), 972 (s), 1,045 (s), 1,249 (s), 1,328 (m), 1,404 (w),
1,461 (m), 1,494 (s), 1,591 (s), 1,660 (s) 2,943 (w), 3,074
1
(w), 3,444 (br) cm-1; H NMR (DMSO-d6, 250 MHz):
1
(w), 3,446 (br) cm-1; H NMR (DMSO-d6, 250 MHz):
d = 3.85–3.97 (m, 4H), 4.25–4.29 (m, 2H), 4.53–4.69 (m,
4H), 5.35 (s, 4H), 5.80–5.98 (m, 2H), 6.79–6.93 (m, 6H),
7.21–7.26 (m, 4H), 7.66–7.70 (m, 6H), 8.29 (s, 2H); 13C
NMR (DMSO-d6, 62.9 MHz): d = 52.6, 62.3, 67.7, 69.1,
d = 3.94–3.96 (m, 4H), 4.26 (s, 2H), 4.50 (dd, 2H,
J1 = 13.8 Hz, J2 = 7.4 Hz), 4.65 (dd, 2H, J1 = 13.9 Hz,
J2 = 3.7 Hz), 5.29 (s, 4H), 5.63–5.65 (m, 2H), 6.89–6.96
123

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J IRAN CHEM SOC (2012) 9:231–250
(m, 6H), 7.24–7.30 (m, 4H), 7.72 (s, 2H), 7.75–7.78 (m, 2H),
7.96–7.99 (m, 2H), 8.27 (s, 2H); 13C NMR (DMSO-d6,
62.9 MHz): d = 57.9, 68.6, 73.1, 74.6, 119.7, 126.0, 127.8,
128.4, 130.8, 131.0, 134.7, 138.6, 138.8, 147.9, 157.8, 163.5,
187.0; anal. calcd. for C38H34N6O8 (702.71): C 64.95, H
4.88, N 11.96%; found: C 64.71, H 4.74, N 12.14%.
J1 = 8.8 Hz, J2 = 1.1 Hz), 6.95 (t, 1H, J = 7.4 Hz),
7.23–7.28 (m, 2H), 7.76 (s, 1H), 7.97 (s, 1H); 13C NMR
(CDCl3, 62.9 MHz): d = 27.9, 29.7, 41.3, 53.3, 68.6, 68.9,
106.4, 114.3, 121.4, 125.3, 129.5, 141.4, 141.8, 148.7,
151.4, 155.2, 157.9; MS: m/z (%) = 412 (M? ?1, 2.0), 411
(M?, 3.6), 255 (2.4), 236 (8.8), 204 (7.2), 180 (15.9), 149
(29.1), 127 (10.4), 111(23.9), 83 (52.6), 55 (100.0); anal.
calcd. for C19H21N7O4 (411.41): C 55.47, H 5.14, N
23.83%; found: C 55.32, H 5.28, N 23.97%.
1,4-Bis((1-(2-hydroxycyclohexyl)-1H-1,2,3-triazol-4-
yl)methoxy)anthracene-9,10-dione(3l)
Isolated as yellow powder; mp 209–210 °C; Rf 0.65 (50%
EtOAc:50% EtOH); IR (KBr): m = 661 (w), 721 (w), 821
(m), 873 (w), 983 (s), 1,047 (s), 1,253 (s), 1,400 (m), 1,450
(m), 1,568 (s), 1,662 (s), 2,860 (m), 2,931 (m), 3,149 (w),
7-((1-(2-Hydroxycyclohexyl)-1H-1,2,3-triazol-4-
yl)methyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (3o)
Isolated as white powder; mp 175–176 °C; Rf 0.1 (EtOAc);
IR (KBr): m = 611 (w), 758 (m), 966 (w), 1,028 (w), 1,080
(w), 1,220 (m), 1,292 (w), 1,406 (w), 1,465 (m), 1,546 (m),
1,604 (w), 1,652 (s), 1,703 (s), 2,862 (w), 2,935 (w), 3,122
3,415 (br) cm-1
;
1H NMR (DMSO-d6, 250 MHz):
d = 1.30–1.40 (m, 6H), 1.65–1.74 (m, 4H), 1.82–2.03 (m,
6H), 3.71–3.79 (m, 2H), 4.19–4.29 (m, 2H), 5.00 (s, 2H),
5.27 (s, 4H), 7.75 (s, 2H), 7.78–7.82 (m, 2H), 7.97–8.02
(m, 2H), 8.24 (s, 2H); 13C NMR (DMSO-d6, 62.9 MHz):
d = 23.8, 24.4, 31.9, 34.8, 63.5, 65.8, 71.3, 122.7, 123.4,
123.9, 125.8, 133.5, 133.6, 141.8, 152.7, 181.9; MS:
m/z (%) = 599 (M? ?1, 0.1), 598 (M?, 1.8), 419 (29.1),
292 (22.5), 240 (77.0), 152 (43.4), 81 (100.0), 55 (98.6);
anal. calcd. for C32H34N6O6 (598.64): C 64.20, H 5.72, N
14.04%; found: C 64.35, H 5.95, N 13.87%.
(w), 3,396 (br) cm-1 1H NMR (CDCl3, 250 MHz):
;
d = 1.38–1.42 (m, 3H), 1.84–2.14 (m, 5H), 3.35 (s, 3H),
3.49 (s, 3H), 3.54 (s, 1H), 3.88–3.95 (m, 1H), 4.09–4.17
(m, 1H), 5.49 (s, 2H), 7.73 (s, 1H), 7.84 (s, 1H); 13C NMR
(CDCl3, 62.9 MHz): d = 24.0, 24.7, 27.9, 29.6, 31.7, 34.2,
41.2, 67.2, 72.3, 106.2, 123.6, 141.1, 141.4, 148.5, 151.3,
155.1; MS: m/z (%) = 361 (M? ?2, 0.7), 360 (M? ?1,
2.4), 359 (M?, 2.8), 252 (1.5), 236 (2.1), 219 (2.4), 197
(2.6), 180 (6.1), 149 (11.5), 123 (14.0), 97 (50.1), 57
(100.0); anal. calcd. for C16H21N7O3 (359.38): C 53.47, H
5.89, N 27.28%; found: C 53.29, H 6.07, N 27.09%.
7-((1-(2-Hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-
yl)methyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (3m)
Isolated as red oil; Rf 0.13 (EtOAc); IR (neat): m = 701
(w), 757 (m), 1,028 (m), 1,071 (m), 1,194 (m), 1,220 (m),
1,454 (m), 1,549 (m), 1,603 (w), 1,657 (s), 1,703 (s), 2,932
1-((1-(2-Hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-
yl)methyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione (3p)
(w), 3,422 (br) cm-1
;
1H NMR (CDCl3, 250 MHz):
Isolated as white powder; mp 174–175 °C; Rf 0.56 (70%
EtOAc:30% EtOH); IR (KBr): m = 704 (m), 947 (m), 1,053
(m), 1,079 (m), 1,186 (m), 1,228 (m), 1,313 (m), 1,370 (m),
1,452 (m), 1,491 (m), 1,550 (s), 1,605 (m), 1,656 (s), 1,704
(s), 2,955 (w), 3,093 (w), 3,257 (br) cm-1; 1H NMR (DMSO-
d6, 250 MHz): d = 3.33 (s, 3H), 3.78 (s, 3H), 3.95–4.00 (m,
1H), 4.23–4.43 (m, 2H), 5.08 (s, 2H), 5.74 (s, 1H), 7.15–7.35
(m, 5H), 7.90 (s, 1H), 8.15 (s, 1H); 13C NMR (DMSO-d6,
62.9 MHz): d = 34.5, 38.3, 41.2, 68.4, 71.4, 111.7, 128.2,
132.3, 133.1, 133.7, 142.4, 142.6, 148.1, 153.4, 155.8, 159.1;
MS: m/z (%) = 384 (M? ?3, 2.1), 383 (M? ?2, 15.7), 382
(M? ?1, 43.1), 381 (M?, 53.8), 322 (72.8), 261 (37.4), 219
(45.1), 180 (35.0), 142 (100.0), 115 (64.5), 67 (50.1); anal.
calcd. for C18H19N7O3 (381.388): C 56.69, H 5.02, N
25.71%; found: C 56.97, H 5.30, N 25.47%.
d = 3.21 (s, 3H), 3.38 (s, 3H), 4.05–4.09 (m, 1H),
4.40–4.48 (m, 2H), 5.42 (s, 2H), 5.62 (dd, 1H, J1 = 8.0 Hz,
J2 = 3.7 Hz), 7.14–7.24 (m, 5H), 7.72 (s, 1H), 7.86 (s,
1H); 13C NMR (CDCl3, 62.9 MHz): d = 27.8, 29.6, 41.2,
64.2, 67.2, 106.3, 124.4, 127.0, 128.6, 128.8, 136.0, 141.6,
141.7, 148.5, 151.3, 155.0; MS: m/z (%) = 382 (M? ?1,
16.1), 381 (M?, 27.7), 261 (14.9), 180 (36.0), 149 (50.0),
121 (47.5), 103 (52.9), 77 (41.7), 57 (100.0).
7-((1-(2-Hydroxy-3-phenoxypropyl)-1H-1,2,3-triazol-4-
yl)methyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (3n)
Isolated as white powder; mp 104–105 °C; Rf 0.16
(EtOAc); IR (KBr): m = 503 (w), 613 (w), 692 (w), 763 (s),
812 (w), 883 (w), 977 (w), 1,045 (s), 1,126 (w), 1,182 (w),
1,230 (s), 1,454 (m), 1,492 (m), 1,548 (m), 1,596 (m),
1-((1-(2-Hydroxy-3-phenoxypropyl)-1H-1,2,3-triazol-4-
yl)methyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione (3q)
1
1,658 (s), 1,706 (s), 2,920 (w), 3,240 (br) cm-1; H NMR
(CDCl3, 250 MHz): d = 3.33 (s, 3H), 3.51 (s, 3H),
3.94–3.97 (m, 2H), 4.41–4.51 (m, 2H), 4.66 (dd, 2H,
J1 = 13.6 Hz, J2 = 3.1 Hz), 5.53 (s, 2H), 6.83 (dd, 2H,
Isolated as white powder; mp 165–166 °C; Rf 0.4 (50%
EtOAc:50% EtOH); IR (KBr): m = 453 (w), 507 (w), 607
123

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237
(w), 688 (w), 754 (s), 881 (w), 952 (w), 1,041 (s), 1,120 (s),
1,180 (m), 1,238 (s), 1,321 (m), 1,458 (m), 1,494 (m),
1,552 (m), 1,602 (m), 1,658 (s), 1,706 (s), 2,947 (w), 3,006
(10.6), 142 (88.2), 121 (22.0), 103 (96.8), 77 (100.0), 50
(44.2); anal. calcd. for C18H16N4O4S (384.40): C 56.24, H
4.20, N 14.57%; found: C 56.39, H 4.42, N 14.30%.
1
(w), 3,240 (br) cm-1; H NMR (DMSO-d6, 250 MHz):
d = 3.21 (s, 3H), 3.68 (s, 3H), 3.76 (d, 2H, J = 5 Hz),
3.94–3.97 (m, 1H), 4.28 (dd, 1H, J1 = 13.7 Hz, J2 = 7.4
Hz), 4.43 (dd, 1H, J1 = 13.8 Hz, J2 = 3.6 Hz), 4.95 (s,
2H), 5.48 (s, 1H), 6.65–6.79 (m, 3H), 7.03–7.09 (m, 2H),
7.77 (s, 1H), 7.83 (s, 1H); 13C NMR (DMSO-d6, 62.9
MHz): d = 29.2, 33.0, 35.8, 52.6, 67.8, 69.3, 106.4, 114.2,
120.5, 124.5, 129.2, 142.7, 142.9, 148.1, 150.5, 153.8,
158.1; MS: m/z (%) = 413 (M? ?2, 5.6), 412 (M? ?1,
20.2), 411 (M?, 32.5), 318 (15.4), 246 (100.0), 218 (17.3),
181 (20.9), 138 (26.1), 109 (35.3), 77 (33.0), 57 (57.7);
anal. calcd. for C19H21N7O4 (411.41): C 55.47; H 5.14; N
23.83%; found: C 55.69, H 5.38, N 23.58%.
2-[1-(2-Hydroxy-3-phenoxypropyl)-1H-[1,2,3]triazol-4-
ylmethyl]-1,1-dioxo-1,2-dihydro-1l6-benzo[d]isothiazol-3-
one (3t)
Isolated as white powder; mp 98–99 °C; Rf 0.7 (EtOAc);
IR (KBr): m = 509 (s), 584 (s), 785 (s), 752 (s), 945 (w),
1,049 (s), 1,122 (s), 1,182 (s), 1,240 (s), 1,301 (s), 1,332
(s), 1,425 (w), 1,463 (s), 1,496 (s), 1,593 (s), 1,732 (s),
1
2,931 (w), 3,085 (w), 3,350 (br) cm-1; H NMR (CDCl3,
250 MHz): d = 3.91 (d, 2H, J = 4.0 Hz,), 4.43–4.65 (m,
4H), 4.96 (s, 2H), 6.78–6.88 (m, 3H), 7.12–7.19 (m, 2H),
7.65–7.89 (m, 4H), 7.92 (s, 1H); 13C NMR (CDCl3,
62.9 MHz): d = 33.6, 53.2, 68.5, 68.9, 114.5, 121.0, 121.2,
125.2, 125.5, 126.7, 129.5, 134.5, 135.1, 137.2, 141.3,
158.2, 158.6; MS: m/z (%) = 414 (M?, 0.4), 380 (0.4), 321
(1.5), 303 (1.1), 278 (0.7), 251 (1.1), 221 (1.8), 181 (1.7),
83 (100.0), 57 (41.8); anal. calcd. for C19H18N4O5S
(414.43): C 55.06, H 4.38, N 13.52%; found: C 55.24, H
4.22, N 13.76%.
1-((1-(2-Hydroxycyclohexyl)-1H-1,2,3-triazol-4-
yl)methyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione (3r)
Isolated as white powder; mp 220–221 °C; Rf 0.44 (50%
EtOAc:50% EtOH); IR (KBr): m = 952 (m), 1,080 (m),
1,230 (m), 1,460 (m), 1,483 (m), 1,548 (m), 1,658 (s),
1,706 (s), 2,941 (w), 3,103 (w), 3,330 (br) cm-1; 1H NMR
(DMSO-d6, 250 MHz): d = 1.07–1.09 (m, 3H), 1.46–1.74
(m, 5H), 3.17 (s, 3H), 3.50 (s, 1H), 3.63 (s, 3H), 3.91– 3.98
(m, 1H), 4.70–4.72 (m, 1H), 4.87 (s, 2H), 7.72 (s, 1H), 7.73
(s, 1H); 13C NMR (DMSO-d6, 62.9 MHz): d = 23.7, 24.4,
29.3, 31.9, 33.0, 34.7, 35.9, 65.7, 71.1, 106.4, 122.3, 142.3,
142.9, 148.2, 150.6, 153.8; MS: m/z (%) = 362 (M? ?3,
2.0), 361 (M? ?2, 12.3), 360 (M? ?1, 42.1), 359 (M?,
65.2), 272 (22.5), 234 (27.0), 206 (17.2), 180 (100.0), 163
(12.1), 137 (35.6), 109 (73.2), 81 (73.6), 55 (68.6); anal.
calcd. for C16H21N7O3 (359.38): C 53.47, H 5.89, N
27.28%; found: C 53.73, H 6.14, N 27.06%.
2-[1-(2-Hydroxycyclohexyl)-1H-[1,2,3]triazol-4-ylmethyl]-
1,1-dioxo-1,2-dihydro-1l6-benzo[d]isothiazol-3-one (3u)
Isolated as white powder; mp 189–190 °C; Rf 0.53
(EtOAc); IR (KBr): m = 513 (s), 584 (s), 677 (s), 748 (s),
810 (s), 846 (s), 954 (s), 1,126 (s), 1,184 (s), 1,263 (s),
1,334 (s), 1,423 (s), 1,458 (s), 1,548(w), 1,591(m),
1,645(w), 1,730(s), 2,858 (s), 3,089 (m), 3,143 (m), 3,359
(br) cm-1; 1H NMR (DMSO-d6, 250 MHz): d = 1.04–1.06
(m, 3H), 1.37–1.41 (m, 2H), 1.49–1.71 (m, 3H), 3.48–3.52
(m, 1H), 3.94–4.03 (m, 1H), 4.61 (s, 1H), 4.78 (s, 2H),
7.62–7.79 (m, 3H), 7.87 (s, 1H), 7.97 (d, 1H, J = 7.6 Hz);
13C NMR (DMSO-d6, 62.9 MHz): d = 23.7, 24.3, 31.8,
33.6, 34.7, 65.9, 71.3, 121.4, 123.3, 124.9, 126.1, 135.0,
135.7, 136.7, 140.3, 158.2; MS: m/z (%) = 365 (M? ?3,
0.2), 364 (M? ?2, 1.2), 363 (M? ?1, 2.1), 362 (M?, 2.3),
334 (19.6), 291 (25.7), 270 (18.5), 171 (16.1), 145 (21.8),
105 (23.1), 81 (100.0), 55 (48.3); anal. calcd. for
C16H18N4O4S (362.40): C 53.03, H 5.01, N 15.46%; found:
C 53.25, H 4.92, N 15.21%.
2-[1-(2-Hydroxy-2-phenyl–ethyl)-1H-[1,2,3]triazol-4-
ylmethyl]-1,1-dioxo-1,2-dihydro-1,6-benzo[d]isothiazol-3-
one (3s)
Isolated as white powder; mp 168–169 °C; Rf 0.66
(EtOAc); IR (KBr): m = 513 (s), 586 (s), 673 (s), 752 (s),
837 (s), 947 (m), 1,062 (s), 1,170 (s), 1,256 (s), 1,325 (s),
1,429 (m), 1,460 (s), 1,595 (m), 1,735 (s), 3,157 (w), 3,321
(br) cm-1; 1H NMR (DMSO-d6, 250 MHz):d = 4.13–4.17
(m, 1H), 4.43–4.49 (m, 1H), 5.14 (s, 2H), 5.49–5.54 (m,
1H), 5.94–5.99 (m, 1H), 7.23–7.32 (m, 3H), 7.39 (d, 2H,
J = 7.1 Hz), 7.76–7.89 (m, 2H), 7.96 (d, 1H, J = 7.2 Hz),
7.63 (d, 1H, J = 7.5 Hz), 8.46 (s, 1H); 13C NMR (DMSO-
d6, 62.9 MHz): d = 33.6, 63.3, 66.4, 121.2, 124.0, 124.9,
126.2, 127.1, 128.2, 128.6, 134.9, 135.6, 136.7, 137.2,
141.0, 158.3; MS: m/z (%) = 385 (M? ?1, 0.4), 384 (M?,
0.6), 354 (46.7), 325 (22.2), 272 (35.2), 196 (15.0), 169
Results and discussion
In this study facile and efficient conversion of terminal
alkynes, sodium azide and epoxides in the presence of a
catalytic amount of metalloanthraquinone for in situ gen-
eration of organic azides followed by an azide-alkyne
cycloaddition (AAC) in one pot which would avoid any
123

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J IRAN CHEM SOC (2012) 9:231–250
purification of potentially unstable organic azide interme-
diates in water is presented.
While the best yield was obtained in water, much lower
yields were observed with organic solvents. To improve the
lack of solubility of the reactants, we also investigated the
micellar effect of SDS in water in the presence of (5.0 mol
%) of catalyst [AQ2Cu(II)] 7 (Table 1, entry 19). Addition
of surfactant (SDS) [99–102] was not effective, and reac-
tion in pure water without using any surfactant gave a high
yield of product. Furthermore, amount of water was
important. When 10 mL of solvent was used, the reaction
proceeded sluggishly and afforded desired product 3a in
low yield. Decreasing the amount of water to 1 mL
improved the yield to 75%, but it was found that the
optimized amount of solvent was 5 mL of water (Table 1,
entries 20–21). The loading levels of the catalyst
[AQ2Cu(II)] 7 have also an effect on the yield. According
to (Table 1, entries 15–18), the optimal catalyst loading in
the synthesis of product 3a is at a concentration of
5.0 mol%. When the amount of the catalyst was reduced,
the yield of the product decreased and the time increase,
whereas raising the catalyst concentration did not lead to an
appreciable increase of the yield and a shorter reaction
time. Also to determine the most suitable reaction condi-
tions, we focused our attention on the effect of temperature
on the model reaction using the optimized amount of cat-
alyst [AQ2Cu(II)] 7 (Table 1, entries 22–24). According to
the results, a strong acceleration and a high yield were
observed at room temperature. It should be noted that,
these results have been correlated by thermodynamic data
based on spectroscopic and electrochemical studies
(Table 2).
Initially, we synthesized a series of the metalloanthr-
aquinone complexes 7–11 by two simple steps from 5 and
6 as shown in Scheme 2. In the first step, 1,4-dihydroxy-
anthraquinone 5 was reacted with ethyl 2-bromoacetate in
the presence of t-BuOK and DMF as a suitable base and
solvent for regio-selective synthesis of mono hydroxyl
anthraquinone 6 in high yield (see the ‘‘Experimental’’ for
details). In the second step ligand 6 was reacted with
various metal chlorides or acetate in methanol for obtains
the metalloanthraquinone 7–11 (see the ‘‘Experimental’’
for details).
Then we applied metalloanthraquinone complexes 7–11
as catalyst for synthesis of b-hydroxy 1,2,3-triazole
derivatives. In order to optimize the reaction conditions,
initially, the reaction of styrene oxide 2a, sodium azide and
phenylacetylene 1a in the presence of metalloanthraqui-
none complexes as a model reaction at room temperature
via a three-component reaction was studied (Table 1).
The results of reaction in the presence of various
[AQ2M] complexes [Cu, Ni, Zn, Fe(Cl), Co (OAc)] are
summarized in (Table 1, entries 1–5). As shown in
Table 1, we found that the use of catalyst [AQ2Cu(II)] 7
through complexation and stabilization of Cu(II) with
the fourth oxygen atom bond in anthraquinone ligand 6,
providing electron density at copper, should be much
more catalytically active than the other metals in terms of
reaction rate, regio-selectivity, and isolated yield of the
corresponding 1,4-disubstituted 1,2,3-triazole (1-phenyl-
2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol) (3a) as the sole
reaction product (Table 1, entry 1) and the other regio-
isomer was not detected in the reaction mixture. Further-
more, in order to show the importance of the catalyst, we
have conducted reactions in the absence of neither the
catalyst nor the metal in the ligand 6, no product was found
(Table 1, entries 6, 7). As can be seen, electron richness at
the metal is largely helpful in the triazole-forming step,
since Cu(OAc)2.H2O which lacks the central oxygen donor
atom provides triazole product in 30% yield after 12 h
(Table 1, entry 8) [51, 97, 98].
Finally, we found that the optimized molar ratio of
styrene oxide with respect to sodium azide, phenylacety-
lene and catalyst [AQ2Cu(II)] 7 (see the ‘‘Experimental’’
for details) was 1.0 mmol/1.1 mmol/1.1 mmol/0.05 mmol
in 5 mL of water at room temperature (Table 1). The
reaction proceeded well and the desired 3a was obtained in
90% yield after 2.5 h.
Preparation and characterization of heterogeneous
nanoparticles [AQ2Cu(II)-APSiO2] 13
In the next step, we focused our attention on investi-
gating the effect of solvents utilizing [AQ2Cu(II)] 7
(5.0 mol%) on our model reaction (Table 1, entries 9–14).
Immobilization of ligand on inorganic supports appears to
be a good way to render them practicable and to improve
O
O
O
O
OH
OH
7: M=Cu
O
O
O
O
O
O
O
O
O
8: M= Ni
Metal salts
DMF , t-BuOK,25 °C
M
9: M= Zn
10: M= Fe (Cl)
11: M= Co (OAc)
O
MeOH, 25 °C
Br
O
OH
O
O
O
O
O
O
5
6
[AQ2 M]
Scheme 2 Structure and procedure for the preparation of homogeneous catalysts 7–11 by two steps
123

J IRAN CHEM SOC (2012) 9:231–250
239
Table 1 Optimization conditions for synthesis of (1-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol) (3a) from styrene oxide (2a), sodium
azide and phenylacetylene (1a) in a 1:1.1:1.1 molar ratio in water at room temperature via a three-component reaction
OH
N
N
O
Optimization
Conditions
+
+
NaN 3
Ph
N
Ph
Ph
Ph
2a
1a
3a
Entry
Catalyst and condition
Solvent
Time (h)
Isolated yield of 3a (%)
1
[AQ2Cu] 7
[AQ2Ni] 8
[AQ2Zn] 9
[AQ2Fe(Cl)] 10
[AQ2Co(OAc)] 11
–
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
EtOH
2.5
2.5
2.5
2.5
2.5
12
90
10
0
2
3
4
0
5
7
6
0
7
6
12
0
8
Cu(OAc).2H2O
[AQ2Cu] 7
[AQ2Cu] 7
[AQ2Cu] 7
[AQ2Cu] 7
[AQ2Cu] 7
[AQ2Cu] 7
12
30
40
2
9
12
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Et2O
12
DMSO
12
12
51
5
DMSO/H2O (1:1)
CH3CN
12
12
THF
12
10
90
30
88
90
85
71
68
56
74
43
[AQ2Cu(II)] 7 (5.0 mol %)
[AQ2Cu(II)] 7 (1.0 mol %)
[AQ2Cu(II)] 7 (10.0 mol %)
[AQ2Cu(II)] 7 (20.0 mol %)
[AQ2Cu(II)] 7 (5.0 mol %)
[AQ2Cu(II)] 7 (5.0 mol %)
[AQ2Cu(II)] 7 (5.0 mol %)
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
2.5
5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
H2O (5 mL)/SDS(1 CMC)
H2O (1 mL)
H2O (10 mL)
[AQ2Cu(II)] 7 (5.0 mol %), 10 °C
[AQ2Cu(II)] 7 (5.0 mol %), 40 °C
[AQ2Cu(II)] 7(5.0 mol %), 100 °C
H2O (5 mL)
H2O (5 mL)
H2O (5 mL)
recoverable catalytic systems that can easily be separated
from the reaction mixture by simple filtration and reused
multiple times without the loss of the activity and selec-
tivity characteristic of the original catalyst. The develop-
ment of organic ligands supported on silica gel have
attracted attention in recent years because industry seeks
more environmentally friendly chemical manufacturing
processes. Silica gel as an inorganic support has a high
surface area (5–800 m2 kg-1) compared with other inor-
ganic supports, ranking these materials at the top of the list
of high-surface area solids [110–112].
Table 2 Thermodynamic parameters of related to the formation of
[AQ2Cu(II)] 7 complex based on spectroscopic and electrochemical
studies
Temperature
(°C)
DGf 9 10-4
DHf 9 10-2
DSf 9 10
(J mol-1
)
(J mol-1
)
(J mol-1
)
10
15
20
25
30
35
40
-0.810
-0.825
-0.842
-0.856
-0.874
-0.889
-0.904
2.464
2.473
2.484
2.496
2.502
2.503
2.504
2.950
2.956
2.962
2.967
2.966
2.965
2.964
As [AQ2Cu(II)] 7 proved to be the best catalyst among
the metalanthraquinone complexes for 1,2,3-triazoles syn-
thesis, we set out to prepare a novel heterogeneous catalyst
by simple impregnation of amino propyl silica gel (AP-
SiO2) with [AQ2Cu(II)] 7. Therefore, it was attempted to
deposit AQ2Cu(II) on APSiO2 (Scheme 3).
their stability, selectivity and the control of their reactivity
through the microenvironment created by the support
[103–109].
For these reasons, a general evolution in catalysis is the
transformation of successful homogeneous catalysts into
In this method of immobilization, the catalyst was
undertaken by stirring a refluxing absolute ethanolic
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J IRAN CHEM SOC (2012) 9:231–250
solution of ligand 6 with APSiO2. The anchoring process
was monitored by UV/vis spectrophotometer. The resulting
supported ligand [AQ-APSiO2] 12 was then separated as a
pale brown powder (see the ‘‘Experimental’’ for details). In
the next step, 1.00 g of the anchored was allowed to reflux
with a solution of Cu(OAc)2.H2O in MeOH for 24 h.
The resulting supported complexes [AQ2Cu(II)-AP-
SiO2] 13 were then separated as a pale blue powder (see the
‘‘Experimental’’ for details). In order to evaluate the Cu
content, the supported catalyst 13 was treated with con-
centrated HCl and concentrated nitric acid to digest the
metal complex and then analyzed by inductively coupled
plasma (ICP) analysis. The Cu content was determined to
be 5.82% W/W (see the ‘‘Experimental’’ for details).
In this experiment, the novel heterogeneous nanoparti-
cles [AQ2Cu(II)-APSiO2] 13 was characterized using FT-
IR spectroscopy, patterned X-ray diffraction (XRD),
atomic force microscopy (AFM) and scanning electron
microscopy (SEM). Also, the active surface area of the
SiO2, APSiO2 and [AQ2Cu(II)-APSiO2] 13 were measured
using a homemade thermogravimetric analyzer [51].
The process related to the complex formation of the
nanocatalyst was also evaluated using FT-IR spectrometry.
Figure 1a, b, c show the FT-IR spectra of ligand 6, silica
gel-anchored [AQ-APSiO2] 12, and copper complex,
[AQ2Cu(II)-APSiO2] 13, respectively. According to the
Fig. 1a, the sharp peak positioned at 1,733.9 cm-1 is
related to the carbonyl group of ester. The absorbance peak
positioned at 1,666.4 cm-1 is correlated to the carbonyl
group in the anthraquinone molecule. Also, the two
absorbance peaks situated at 1,637.5 and 1,593.1 cm-1 are
related to the carbonyl group, hydrogen bonded with the
hydroxyl group positioned at position 1 in the anthraqui-
none molecule [113]. The silica gel-anchored [AQ-AP-
SiO2] 12 results to detect two absorbance peaks for the
carbonyl group at 1,643.2 and 1,542.9 cm-1, respectively.
According to the spectrum Fig. 1b, the broad peak posi-
tioned at 1,643.2 cm-1 is the combination of the absor-
bance peak of carbonyl group of the amide and that
hydrogen bonded with hydroxyl group (position 1) in the
anthraquinone molecule. Whereas the peak situated at
1,542.9 cm-1 is correlated to latter carbonyl group in the
anthraquinone molecule. Also, according to the FT-IR
spectrum of copper complex [AQ2Cu(II)-APSiO2] 13
(Fig. 1c), temporarily the copper complex was formed,
three independent absorbance peaks were evaluated for the
carbonyl functional groups. These include the carbonyl
group of amide at 1,571.9 cm-1 location, the carbonyl
group of anthraquinone, which coordinated with copper at
1,433.0 cm-1 position, and finally the not-coordinated
(free) carbonyl group of anthraquinone positioned at
1,527.5 cm-1. Also, based on the FT-IR spectra, the strong
peak at around 677 cm-1 is related to the stretching of the
Cu–O bond [51].
According to the smoothed XRD image shown in Fig. 2,
the strong peak at around 2h = 15° is related to the silica
gel support. Also, the peaks positioned at 2h equal to
around 28, 37, 55, 65 and 78° are correlated to the different
copper phases including Cu(111) Cu(220), Cu(222),
Cu(331) and Cu(220), respectively.
In this experiment, the strongest peak (2h = 37°) related
to copper species was used to evaluate the average diam-
eter of copper species supported on silica gel as solid
support based on Debye–Scherer equation [51].
This was calculated to *70 nm which is in good
agreement with the SEM Fig. 3a, 2-dimensional (2-D) and
3-dimensional (3-D) images of AFM (Fig. 3b, c). The
normal diameter of the copper nanoparticles supported on
silica gel support was also graphically evaluated according
to the voltage profile of the AFM image as shown in
Fig. 3d. The voltage profiles in different parts of the AFM
image reveals the distribution of the copper species ranging
from 35 to *170 nm.
The correlation between the relative percentages of the
copper nanoparticles with the diameter is graphically
evaluated in the histogram shown in Fig. 4.
The increase in the active surface area of the solid
support when doped with copper species was evaluated
based on the surface adsorption of nitrogen at room tem-
perature as illustrated in Fig. 5. According to the nitrogen
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Cu
O
OH HO
O
O
O
O
Cu(OAc)2.H2O
MeOH , Reflux
O
O
EtOH , Reflux
APSiO2
O
O
HN
NH
HN
NH
OH
Si
O
Si
Si
O
Si
EtO
EtO
O
6
O
O
EtO
O
EtO
O
O
[AQ-APSiO2] 12
[AQ2Cu(II)-APSiO2] 13
Scheme 3 Structure and procedure for the preparation of heterogenous catalysts 13 by two steps
123

J IRAN CHEM SOC (2012) 9:231–250
241
Fig. 1 The FT-IR spectra of a ligand 6, b [AQ-APSiO2] 12, c [AQ2Cu(II)-APSiO2] 13
nanoparticles supported on silica gel. According to the
thermogram, the significant decrease in the weight per-
centage of the copper nanoparticles supported on silica gel
at *180 °C is related to the decomposition of [AQ2Cu(II)-
APSiO2] 13. Also, a slow increase in the weight percentage
at *340 °C is related to the oxidation of copper species
and formation of copper oxide. Decrease in the weight at
around 800 °C is due to the decomposition of silica gel
support. The end part of the thermogram shows the amount
of copper oxide formed. This value is used to estimate the
amount of copper species supported on silica gel. In this
experiment, the amount of copper nanomaterials supported
on silica gel was calculated to be 6.11%. Also, the calcu-
lations related to the thermogram estimate a 2:1 ratio for
ligand to copper according to the copper complex
formation.
170
150
130
110
90
Si
Cu(220)
Cu(111)
Cu(222)
70
50
Cu(220)
Cu(331)
30
10
5
15
25
35
45
55
65
75
85
95
2-Theta-Scale
Fig. 2 Smoothed XRD image of copper nanoparticles supported on
silica gel support
adsorption isotherms, the active surface area was evaluated
to around 103, 247 and 369 m2 kg-1, for SiO2, APSiO2
and [AQ2Cu(II)-APSiO2] 13, respectively.
There was also an evidence which based on the UV–Vis
spectrum of copper complex as shown in Fig. 7. As clearly
observed in this spectrum, large red shift is observed from
450 to 520 nm in accordance with the formation of
[AQ2Cu(II)] 7 complex during the addition of ligand. The
insets of Fig. 7 clearly show the correlation between the
absorbance and different ratio of copper–ligand at 450 and
520 nm. The associated point between the extrapolations of
the two distinct linear relationships between the different
According to the nitrogen adsorption isotherms, the
active surface area was evaluated to around 103, 247 and
369 m2 kg-1, for SiO2, APSiO2 and [AQ2Cu(II)-APSiO2]
13, respectively. In this experiment, the number of ligand
coordinated with copper nanoparticles was also evaluated
using thermogravimetric analysis and UV–vis. spectros-
copy. Figure 6 reveals the thermogram of copper
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242
J IRAN CHEM SOC (2012) 9:231–250
Fig. 3 Microscopic images
including a SEM, b 2-D AFM,
c 3-D AFM and d voltage
profile of copper species
supported on silica gel
35
30
25
20
15
10
5
0
37
43
51
65
98
135
167
Average Size of Copper Nanoparticles (nm)
Fig. 4 The histogram showing the normal distribution of copper
species supported on silica gel
Fig. 5 Nitrogen adsorption isotherms of a SiO2, b APSiO2 and
c [AQ2Cu(II)-APSiO2] 13
ratios of ligand to copper reveals 2:1 ratio for ligand to
copper. The extracted results from spectrum revealed the
value of 2.294 9 103 for [AQ2Cu(II)] 7 formation constant.
For further confidence about the complex formation as
well as to confirm the ratio of 2:1 for ligand to copper in
[AQ2Cu(II)] 7 complex, the electrochemical properties of
both ligand and [AQ2Cu(II)] 7 complex were investigated
[72]. These properties are related to the change in the elec-
tronic state of the ligand, when contributes to the complex-
ation process. In this experiment, the voltammogram of
2.5 9 10-3 M solution of each free ligand and complex in
deaerated DMSO as solvent in the presence of 0.1 M TBAB
as supporting electrolyte was recorded with the scan rate of
100 mV s-1 using glassy carbon as working and the two
platinum rods as counter and pseudo-reference electrodes,
respectively. The cyclic voltammograms of ligand and
complex are shown in Fig. 8. The anthraquinone ligand
6 (1A), exhibits two redox couples (E1/2 = -0.83 V
and -0.12 V vs. Fc/Fc?) convertible to the stepwise
123

J IRAN CHEM SOC (2012) 9:231–250
243
one-electron reductions of 6 and formation of reduced spe-
cies. Also, in accordance with the voltammogram (1B)
shown in Fig. 1, the redox couples of derivative anthraqui-
none oxygen-coordinated copper(II) complex was nega-
tively shifted (E1/2 = -0.87 V and -0.19 V vs. Fc/Fc?)
comparing with those related to the free ligand. Unexpect-
edly, this reveals that, the [AQ2Cu(II)] 7 complex shows
partially anodic shift. However, several bonds are formed
between the oxygen of carbonyl group with copper(II), but
the lack of hydrogen bond is probably the main reason for the
negative shift of complex comparing to that of free ligand. It
seems that the higher entropy is the main reason for the
stability of the complex (Kf = 2.294 9 103). For this pur-
pose, the spectroscopic and cyclic voltammetric studies of
the [AQ2Cu(II)] 7 complex were studied in different tem-
peratures ranging from 10 to 40 °C using Van’t Hoff equa-
tion and Gibbs free energy as shown below.
Table 2 shows the thermodynamic results based on
spectroscopic and electrochemical studies. According to
the results, higher entropy is the main phenomenon for
stabilization of complex at room temperature.
The principle advantages of this immobilization tech-
nique include the absence of any complexity in the
immobilization process, the widespread availability of sil-
ica gel inorganic supports, the rapid and experimental
simplicity of the procedure and the fact that the purity of
the immobilized complex can be better assessed.
1A: Ligand 6
2.00E-05
1B: [AQ2Cu(II)] 7
1.50E-05
10µA
1.00E-05
5.00E-06
0.00E+00
-2.1
-1.6
-1.1
-0.6
-0.1
-5.00E-06
0.4
-1.00E-05
-1.50E-05
-2.00E-05
Fig. 8 Cyclic votammograms of 1A ligand 6 (5 9 10-3) and 1B
[AQ2Cu(II)] 7 complex using Cu(OAc)2ꢀH2O (2.5 9 10-3) in DMSO
(0.1 M TBAB) at glassy carbon working electrode with scan rate
100 mVs-1 under Ar versus Fc/Fc? at room temperature
Fig. 6 The thermogram of copper nanoparticles supported in silica
gel
Fig. 7 UV–vis spectra on
successive of 6 (1.0 9 10-4
with Cu(OAc)2ꢀH2O
450 nm
520 nm
2.5
2
)
0.6
0.5
0.4
0.3
0.2
0.1
0
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
(2.5 9 10-3) each inject 10 lL
in DMSO. (Insets the
correlation between absorbance
with different ratio of copper–
ligand)
0
0.5
1
1.5
2
2.5
3
3.5
0
0.5
1
1.5
2
2.5
3
3.5
[Metal/Ligand]
[Metal/Ligand]
1.5
1
0.5
0
Wavelength (nm)
123

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J IRAN CHEM SOC (2012) 9:231–250
in the reaction moiety, resulting from the addition of
sodium azide to the alkyne, was not detected [51].
DG ¼ DH ꢁ TDS
d ln K
ꢁDHꢂ
ꢁDGꢂ
¼
ln K ¼
As it can clearly be seen for the heterogeneous catalyst in
comparison with the homogeneous catalyst in Table 3, the
regio-specificity has remained unchanged and decrease in
reaction times are also observed which could be attributed
to the significant increase in the activity of the heteroge-
neous catalyst. This might be due to the nano-sized con-
struction of catalyst and the uniform dispersion of metallic
nanoparticles on high specific surface area of silica gel.
To check the feasibility of this procedure on a large-
scale operation, we carried out the cycloaddition of
2-(phenoxymethyl)oxirane (2b) and NaN3 with phenyl-
acetylene on a 50 mmol scale in the presence of the
homogeneous and heterogeneous catalyst. As expected, the
reaction proceeded similarly to the experiment on a smaller
scale, except that a little prolonged reaction time was
required (Table 3, entry 3).
dð1=TÞ
R
RT
Homogeneous and heterogeneous catalytic synthesis
of b-hydroxy 1,4-disubstituted 1,2,3-triazole
derivatives
Finally for evaluate the scope of this reaction under the
optimized conditions, and because a suitable methodology
for converting a homogeneous catalyst into a heteroge-
neous catalysts provided the chance of recovery of the
catalyst for the successive multiple uses, we were
encouraged to carry out the reaction of epoxides, sodium
azide, and terminal alkynes in the presence of homoge-
neous and heterogeneous catalysts at room temperature to
give exclusively the corresponding b-hydroxy 1,4-disub-
stituted 1,2,3-triazole derivatives 3 in high yields.
Furthermore, we investigated the copper scavenger
aspect of ligand 6 and [AQ-APSiO2] 12 in uncomplexed
forms. To demonstrate the scavenging abilities, we set up
the reaction of styrene oxide 2a, sodium azide, phenyl-
acetylene 1a and Cu(OAc)2 H2O as a model reaction. The
reaction proceeded well and the desired 3a was obtained in
90% yield after 4.5 h. The filtrate solvent was free from
any detectable copper contamination, checked with ICP
method. Overall, this result clearly indicated the catalytic
benefits and an additional advantage offered by the sim-
plicity of the operational procedure obtained by mixing all
starting materials for the reaction (epoxide 2a–2c, sodium
azide, alkyne 1a–1j, Cu(OAc)2ꢀH2O, ligand 6 or [AQ-
APSiO2] 12 and water) without needing any synthesized
homogeneous catalyst [AQ2Cu(II)] 7 or heterogeneous
catalyst [AQ2Cu(II)-APSiO2] 13.
Then in order to show the generality, versatility and
functional group tolerance procedure, we applied similar
reaction conditions in the presence of both homogeneous
and heterogeneous catalysts for the preparation of struc-
turally diverse b-hydroxy 1,4-disubstituted 1,2,3-triazole
from different epoxides and terminal alkyne. The reactions
proceeded smoothly and efficiently in this optimized
reaction condition with high isolated yields in short reac-
tion times that could be applied easily for large-scale
operations (Table 3). As shown in Table 3, steric and
electronic variation in the terminal aliphatic alkyne or
epoxides was tolerated and did not change the efficiency of
the reaction. Heteroatom containing substituents including
anthraquinones, theophylline, theobromine, and saccharine
in the alkynes were also readily introduced into the triazole
skeleton as potential biologically active compounds
(Table 3). As expected, internal alkynes gave no reaction.
The reaction behavior is in agreement with a mechanism
involving the formation of a Cu acetylide species, probably
on the heterogeneous surface (Fig. 9).
The major advantage of using heterogenized [AQ2Cu
(II)-APSiO2] 13 as catalyst in comparison with [AQ2
Cu(II)] 7 is the ease with which they can be recycled as
stable species from the reaction mixture and reused. Thus,
we carried out the reactions using styrene oxide and
phenylacetylene as the model to test the recyclables of
[AQ2Cu(II)-APSiO2] 13. The results in Table 4 show that
this heterogeneous catalyst could be reused in ten consec-
utive trials by simple filtration without any critical loss of
activity. After ten consecutive reactions, the recovered
[AQ2Cu(II)-APSiO2] 13 was found to contain 5.71%
(W/W) of copper based on ICP analysis, which is compa-
rable to the initial value of 5.82% (W/W), indicative of less
than *1.75% leaching cycles. It is very clear that the
catalytic activity of the present system is intact even after
ten cycles. In order to evaluate the thermal stability of
the heterogeneous catalyst, [AQ2Cu(II)-APSiO2] 13 was
refluxed in DMF for 12 h. Then, the heterogeneous catalyst
was washed with water and dried under vacuum condition.
In the cases where styrene oxide was utilized as epoxide,
product 3 was achieved as a result of the cleavage of the
epoxide with sodium azide in a regio-selective manner with
preferential attack at the less hindered site. Encouraged by
the results achieved with styrene oxide, our attention was
changed to various epoxides.
The regio-selective property of products was clarified by
the following observations: in a similar 1,4- and 1,5-
substituted 1,2,3-triazole systems, it was concluded that,
the triazole proton in 1,4-substituted triazoles was always
shifted downfield compared to 1,5-substituted triazoles [48,
51]. The only proton of the triazolyl ring (H-5) in the
products was observed as a singlet in the range of d
7.28–7.73 [51]. Furthermore, the presence of N–H triazoles
123

J IRAN CHEM SOC (2012) 9:231–250
245
Table 3 Regio-selective
synthesis of b-hydroxy
1,4-disubstituted 1,2,3-triazoles
[AQ2Cu(II)-
[AQ2Cu(II)] 7
APSiO2] 13
Product
3
Entry
Alkyne
1
Epoxide
Isolated
Time
Isolated
Yield
[%]
from various epoxides
Time
[h]
2
Yield
[h]
(1.0 mmol), terminal alkynes
(1.1 mmol) and sodium
azide (1.1 mmol) in the
presence of homogeneous and
heterogeneous catalysts
(5.0 mol%) in 5 mL water at
room temperature
[%]
N
N
O
OH
Ph
Ph
N
1
2
2.5
3.5
90
92
1
91
Ph
2a
3a
N
O
O
N
N
Ph
OH
Ph
O
O
Ph
Ph
1.5
90
3b
2b
2b
N
N
N
Ph
O
OH
Ph
O
O
3
4
5
88a
95
3
90a
91
3b
1a
N
N
N
OH
Ph
3.5
1.5
2c
3c
O
O
O
O
5
6
7
5
6
6
87
90
90
4
90
91
89
Ph
N
N
3d
N
2a
HO
Ph
O
O
O
O
O
O
N
O
4.5
4.5
O
Ph
3e
N
N
HO
Ph
O
2b
2c
O
O
1b
O
O
N
N
3f
N
HO
O
O
O
N
O
O
3g
Ph
N
8
6
83
4.5
85
N
N
N N
OH
HO
2a
Ph
Ph
O
O
O
O
O
O
9
7
7
92
95
5
5
91
89
O
3h
Ph
N
N
N
N N
N
2b
O
O
O
Ph
OH
HO
Ph
O
O
O
O
O
O
O
1c
10
3i
N
N
N
N
N
N
2c
OH
HO
123

246
J IRAN CHEM SOC (2012) 9:231–250
Table 3 continued
[AQ2Cu(II)-
[AQ2Cu(II)] 7
APSiO2] 13
Product
3
Entry
Alkyne
1
Epoxide
2
Isolated
Isolated
Time
[h]
Time
[h]
Yield
[%]
Yield
[%]
3j
O
O
O
O
O
N
N
11
6
7
7
79
93
86
4.5
81
92
85
Ph
N
N
N
N
OH
HO
Ph
Ph
2a
O
O
O
O
O
O
3k
O
O
O
N
N
O
12
5
N
N
Ph
N
N
OH
Ph
HO
Ph
2b
O
O
3l
O
O
O
O
1d
O
N
N
13
5
N
N
N
N
OH
HO
2c
O
N
N
3m
O
N
N
Ph
N
14
15
5
6
87
96
3.5
4.5
88
93
N
HO
N
Ph
N
O
2a
O
N
N
O
N
N
N
3n
N
N
O
N
N
O
N
O
HO
Ph
Ph
O
O
2b
1e
N
N
O
O
N
N
3o
N
16
17
N
6
5
92
82
4.5
3.5
90
89
HO
N
O
2c
O
N
O
OH
O
N
3p
3q
N
N
N
Ph
Ph
N
N
O
2a
O
O
N
N
N
Ph OH
O
O
N
N
Ph
N
O
N
18
19
6
6
97
94
4.5
4.5
94
92
N
N
N
O
N
2b
O
N
O
OH
N
N
N
N
3r
3s
1f
N
N
O
N
2c
O
HO
Ph
Ph
N
N
O
20
5
88
3.5
90
N
2a
S
O
O
O
HO
O Ph
O
N
N
3t
N
N
O
O
S
Ph
O
O
21
22
6
6
97
86
4.5
4.5
97
86
N
S
O
O
2b
1g
O
N
N
N
O
HO
N
3u
S
O
2c
O
123

J IRAN CHEM SOC (2012) 9:231–250
247
Table 3 continued
[AQ2Cu(II)-
APSiO2] 13
[AQ2Cu(II)] 7
Product
3
Entry
Alkyne
1
Epoxide
Isolated
Time
Isolated
Time
2
Yield
[h]
Yield
[%]
[h]
[%]
HO
HO
N
N
HO
Ph
23
24
6
6
89
90
4
87
90
N
1h
3v
O
OH
Ph
OH
OH
N
N
N
H3C
Ph
H3C
4
4
CH3
1i
3w
CH3
2a
OH
Ph
N
N
N
1j
25
26
6
80
-
84
-
3x
O
Ph
24
24
24
Cl
2a
No reaction
O
1k
O
Ph
27
24
-
-
a
2b
The reaction performed
on a 50-mmol scale
Under the same reaction conditions as in Table 4, the
reaction proceeded well and the desired 3a was obtained at
90% yield after 1 h. Overall, catalyst [AQ2Cu(II)-APSiO2]
13 demonstrated good stability and activity for further
studies.
On the other hand, based on our previous studies and
other works in this pathway, the participation of a metal
azide as the catalytically active species suggests that, the
mechanism of epoxide ring opening involves azide deliv-
ery from the catalyst as well as epoxide activation by the
[AQ2Cu(II)] 7 catalyst. Moreover, it can be concluded that,
the reaction rate in the present reaction should be affected
not only by the complexation of NaN3 with [AQ2Cu(II)] 7
Mechanistic considerations
-
A proposed mechanism [48, 49, 51] for the formation of
b-hydroxy 1,4-disubstituted 1,2,3-triazole may comprise
two possible pathways in which [AQ2Cu(II)] 7, has a dual
catalytic role as a bifunctional catalyst which combines two
reactions in ‘‘one-step’’: I and II. Pathway I includes
[AQ2Cu(II)] 7 catalyzed 2-azido-1-phenylethanol forma-
tion from styrene oxide (2a) and sodium azide (Fig. 9,
pathway I). For pathway I, while the phenylacetylene (1a)
consumption and also the generation and the disappearance
of the 2-azido-1-phenylethanol intermediate, were moni-
tored by gas chromatography (GC) analysis and thin layer
chromatography (TLC) runs of the reaction mixture, we
found that the 2-azido-1-phenylethanol is formed easily
(within the first 45 min of the reaction) and the rate-
determining step (RDS) was found to be the 1,3-dipolar
cycloaddition step. The FT-IR spectrum of 2-azido-1-
phenylethanol displayed the characteristic azido stretching
frequency at 2,104 cm-1. In order to check the validity of
RDS of the reaction, the 2-azido-1-phenylethanol was
separately reacted with phenyl acetylene in the presence of
a catalytic amount of [AQ2Cu(II)] 7. The formation of
corresponding product 3a was monitored via GC analysis
and TLC runs. It was observed that the reaction was
completed within 2 h. These results indicated that the RDS
is involved in pathway II.
complexes, but also by the dissociation of the N3 anion
from the adduct and simultaneous activation of epoxide
and azide by two different catalyst molecules. In order to
validate the catalyst role in pathway I, the styrene oxide
and sodium azide were reacted in the absence of catalyst. It
was found that, only a trace amount of 2-azido-1-phenyl-
ethanol had been formed.
For pathway II, first, activation of phenylacetylene (1a)
takes place by the insertion of [AQ2Cu(II)] 7 to the ter-
minal alkyne, forming acetylide intermediate A, which
facilitates the [3 ? 2] cycloaddition, between carbon–car-
bon triple bond of the 2-azido-1-phenylethanol and in situ-
generated intermediate B, to give the Cu–C (triazole)
C. Taking into account the observations that internal
alkynes such as chloro phenylacetylene (1k), that did not
afford the corresponding triazoles (the initial acetylene was
recovered), we found it reasonable to propose the
involvement of the acetylide intermediate A as a partner of
the [3 ? 2] cycloaddition. At last, protonolysis of the Cu–
C bond of intermediate C by aqueous media or phenyl-
acetylene afforded the corresponding 1,2,3-triazoles 3a and
regenerates the [AQ2Cu(II)] 7 catalyst for further reactions
(Fig. 9, pathway II).
As another validation for the formation of acetylide
intermediate A, encouraged by previous reports, phenyl
123

248
J IRAN CHEM SOC (2012) 9:231–250
Table 4 Catalyst recyclability of [AQ2Cu(II)-APSiO2] 13 in 1 h
Reaction run
1st
91
2nd
89
3th
90
4th
89
5th
89
6th
88
7th
89
8th
85
9th
83
10th
83
Isolated yield (%)
-
AQCuAQ + N3
-
2-azido-1-phenylethanol
HO
N
Ph
N
OH
N
N3
Ph
O
AQCuAQ
CuAQ2
Ph
-
Ph
N3
2a
B
-
H+
OH
Ph
N
N
N
Pathway II
Ph
CuAQ2
Ph
Pathway I
CuAQ2
A
Ph
N3
-
C
N3
-
O
H+
H+
AQCuAQ
O
AQCuAQ
-
N3
Ph
AQCuAQ
AQCuAQ
Ph
H
-
AQ2Cu
N3
OH
N
N
1a
N
Ph
Ph
3a
Fig. 9 Reaction mechanism proposed for the [AQ2Cu(II)] 7 as a bifunctional catalyst for the synthesis of b-hydroxy 1,4-disubstituted 1,2,3-
triazole (pathway I and pathway II) in a one-pot, two-step and three-component reaction
acetylene and [AQ2Cu(II)] 7 were mixed in a separate
experiment in aqueous media, while the pH of water as a
solvent was monitored. A 0.56 Unit decrease in pH after
15 min was detected, indicative of terminal proton release
to the water, due to the initial coordination of phenyl
acetylene to [AQ2Cu(II)] 7 to form acetylide intermediate
A (Fig. 9).
unstable. Furthermore, the catalyst could be recovered and
reused by simple filtration of the reaction mixture and was
recycled ten times showing negligible copper leaching. In
their uncomplexed form of homogeneous and heteroge-
neous 1,4-dihydroxyanthraquinone-copper(II) catalyst, the
anthraquinone ligand 6 and [AQ-APSiO2] 12 is a very
efficient copper scavenger that are capable to catalyze the
1,3-dipolar cycloaddition reaction without the pre-synthe-
sis of catalysts.
Conclusions
Acknowledgments We appreciate the funding from Shiraz Uni-
versity research council for the financial support in work. We are
grateful to Dr. M. Nakoei and Mr. M. Sorouri for their helps and
comments during the progress of this work. We are also thankful to
Mr. M.S. Darvish Tafvizi and Mr. H. Sajedian Fard for running the
NMR and mass spectra.
In conclusion, we have developed and characterized the
first example of homogeneous and heterogeneous 1,4-
dihydroxyanthraquinone-copper(II) catalyst in an efficient,
one-step and one-pot ‘‘click reaction’’ for the synthesis of
b-hydroxy 1,4-disubstituted 1,2,3-triazoles from a variety
of epoxides, terminal alkynes and sodium azide in a regio-
selectivity pure form. The reaction was experimentally
simple with a high yield and a short reaction time in water
and the method avoids isolation and handling of in situ-
generated organic azide intermediates that are potentially
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