Copper aluminate spinel in click chemistry: An efficient heterogeneous nanocatalyst for the highly regioselective synthesis of triazoles in water

Article abstract of DOI:10.1055/s-0039-1690719

An expeditious protocol for the one-pot synthesis of 1,4-disubstituted (β-hydroxy)-1,2,3-Triazoles in an aqueous medium has been developed using copper aluminate nanoparticles. This heterogeneous catalytic system was found to drive a multicomponent click reaction between organic azides (generated in situ from epoxides or halides) and terminal aliphatic or aromatic alkynes in up to 96percent yield without the need for a reducing agent. Structurally diverse 1,2,3-Triazoles were synthesized in good to excellent yields, and the catalyst could be easily separated by simple filtration, recycled, and reused in six subsequent cycles.

Full text of DOI:10.1055/s-0039-1690719

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© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–G
letter
A
en
D. Khalili et al.
Letter
Synlett
Copper Aluminate Spinel in Click Chemistry: An Efficient Hetero-
geneous Nanocatalyst for the Highly Regioselective Synthesis of
Triazoles in Water
Dariush Khalili*
Leila Kavoosi
N
R1
N
N
R1-X
or
R
Ali Khalafi-Nezhad
NaN ,
C CH,
R
CuAl2O4 NPs (5 mg)
3
or
90 °C, H2O
O
R2
Department of Chemistry, College of Sciences,
Shiraz University, Shiraz, 71454, Iran
Khalili@shirazu.ac.ir
N
R
N
R2
N
N
OH
N
N
OH
+
R2
R
R
Advantages:
R2 = aryl
2 = alkyl
*simple removal of the catalyst
*short reaction time
*high yields
*high diversity
*green solvent
Received: 01.10.2019
Accepted after revision: 03.10.2019
Published online: 04.11.2019
click-chemistry reaction as itemized by Sharpless in 2001,
giving a high yield, few byatalysis, and sensor material-
sproducts, and easily purified products and displaying high
regio- and stereospecificity.3,7 Two revolutionary modifica-
tions based on copper- and ruthenium-catalyzed azide–
alkyne cycloaddition reported in 20028 and 2005,9 respec-
tively, not only reduced the reaction time and temperature,
but also gave the desired 1,4-disubstituted and 1,5-disub-
stituted triazoles, respectively.
Despite the considerable progresses in homogeneous
copper-catalyzed azide–alkyne cycloaddition (CuAAC) in
recent years, there are some inherent shortcomings associ-
ated with these catalytic systems in industry. These include
the formation of homocoupling byproducts in the case of
copper halide-catalyzed reaction and the contamination of
the target products by copper. The latter is particularly im-
portant in the pharmaceutical industry and it results in the
need to recover and remove the catalyst10,11 because, for
pharmaceutical applications, the content of metal contami-
nants should not exceed 15 ppm. For example, even in the
case of 0.01 mol% of a copper catalyst, about 25 ppm of
metal contaminants can be detected in the products from a
CuAAC reaction.10 Hence, there are ongoing efforts to
achieve CuAAC reactions by heterogeneous catalysis using
materials such as silica, polymers, zeolites, or activated car-
bon as supports.6,11,12
DOI: 10.1055/s-0039-1690719; Art ID: st-2019-u0382-l
Abstract An expeditious protocol for the one-pot synthesis of 1,4-
disubstituted (-hydroxy)-1,2,3-triazoles in an aqueous medium has
been developed using copper aluminate nanoparticles. This heteroge-
neous catalytic system was found to drive a multicomponent click reac-
tion between organic azides (generated in situ from epoxides or ha-
lides) and terminal aliphatic or aromatic alkynes in up to 96% yield
without the need for a reducing agent. Structurally diverse 1,2,3-tri-
azoles were synthesized in good to excellent yields, and the catalyst
could be easily separated by simple filtration, recycled, and reused in six
subsequent cycles.
Key words click chemistry, copper catalysis, triazoles, epoxides,
azides, alkynes
The discovery of the azide–alkyne Huisgen 1,3-dipolar
cycloaddition has led to the 1,2,3-triazole scaffold becom-
ing important in synthetic chemistry.1 This importance of
1,2,3-triazoles arises from a number of their properties,
such as their chemical stability to high temperatures or to
oxidizing, reducing, or hydrolyzing conditions; their aro-
matic nature; their high dipole moment (<5 D); and their
capacity to form hydrogen bonds.2,3 Although 1,2,3-tri-
azoles are not formed in nature, synthetic compounds con-
taining this structure have shown interesting biological
properties.4 In addition to this range of characteristics,
1,2,3-triazoles are outstanding mimetic of the amide bond
in bioconjugation reactions; moreover, they have a wide
range of applications in various other fields, such as poly-
mer and dendrimer chemistry, biochemistry, and materials
chemistry.2,5,6 The original Huisgen reaction of terminal
alkynes with aliphatic azides proceeds at high tempera-
tures and with prolonged reaction times to give both 1,5-
and 1,4-disubstituted 1,2,3-triazoles. The modified Huisgen
1,3-dipolar cycloaddition reaction fulfills the criteria for a
Because of its prominent features such as its benign and
inexpensive composition, high thermal stability, high me-
chanical stability, low surface acidity, and hydrophobicity,
spinel copper aluminate (CuAl2O4) has become a subject of
current research in the fields of materials science, catalysis,
photocatalysis, and sensor materials.13 However, spinel cop-
per aluminate and its composites have rarely been used as
heterogeneous copper catalysts in organic synthesis, and
there are just few reports on a synthesis of imidazol[1,2]
pyridines,14 a solvent-free synthesis of xanthanedione de-
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
D. Khalili et al.
Letter
Synlett
Table 1 Characterization Data for CuAl2O4 Nanoparticles
Analysis
Results
BET surface area
Pore volume
Pore size
XRD
23.873 m2·g–1
0.1539 cm3·g–1 (BJH adsorption: cumulative volume of pores)
25.308 nm (pore size distribution)
monophasic spinel cubic (Fd-3m with a lattice size of 8.064 Å; JCPDS 33-0448)18
after loss of H2O, the catalyst showed stability at least to 1000 °C under air.
irregularly shaped grains, along with some uniform globular nanocrystals
Cu: 53.11, Al: 5.31; O: 27.80 (mass %)
TG
SEM
EDX
TEM
20–30 nm
rivatives,13e and a catalytic oxidation of benzylic alcohols.15
Consequently, an investigation of the application of spinel
copper aluminate in organic synthesis is of considerable in-
terest. As an extension of our researches on the develop-
ment of heterogeneous catalytic systems,16 we present the
first report of a highly regioselective synthesis of 1,4-disub-
stituted (-hydroxy)-1,2,3-triazoles from alkynes and or-
ganic azides, generated in situ under ecofriendly condi-
tions, with catalysis by spinel CuAl2O4 nanoparticles. More-
over, the reaction does not require any solid support or
sacrificial reducing agent. This method not only provides
simpler experimental procedures but also bypasses safety
issues associated with the handling of the potentially ex-
plosive azides.
delight, H2O turned out to be the best medium for the reac-
tion and it gave an 89% yield of product 3a after 45 minutes
(entry 7). Increasing the reaction temperature to 90 °C re-
sulted in an excellent 97% yield of 3a (entry 8). Finally, the
effect of the catalyst loadiction and higher yields were ob-
taineng on the reaction yield was investigated. Increasing
the amount of the catalyst to 10 mg (entry 9) had no signif-
icant effect on the product yield, whereas decreasing the
amount of catalyst to 2.5 mg decreased the yield to 79% (en-
try 10). Only an 8% yield of 3a was obtained when no cata-
lyst was present (entry 11). Having established the optimal
conditions [CuAl2O4 (5 mg), H2O, 90 °C], we explored the
scope and limitations of this catalytic system in CuAAC re-
First, CuAl2O4 was prepared according by a simple and
efficient reported procedure based on a modified Pechini
sol–gel method.17 The resulting catalyst was fully character-
ized by Fourier-transform infrared spectroscopy (FTIR), X-
ray diffraction (XRD), field-emission scanning electron mi-
croscopy (FESEM), transmission electron microscopy
(TEM), energy-dispersive X-ray analysis (EDX), Brunauer–
Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH)
analyses, X-ray photoelectron spectroscopy (XPS), and ther-
mogravimetric analysis (TG) [see Supporting Information
(SI)]. After evaluating varied calcination conditions, we
found that calcination at 950 °C for 10 hours was optimal,
and the relevant characterization data for the resulting cat-
alyst are summarized in Table 1.
To determine the optimal conditions for the CuAAC re-
action, the catalytic activities of spinel CuAl2O4 nanoparti-
cles were examined in a model reaction of ethynylbenzene
(1a), benzyl bromide (2a), and sodium azide without any
reducing agent. The results are summarized in Table 2.
Although the reaction did not proceed well in aprotic
organic solvents, even under reflux conditions (Table 2, en-
tries 1–3), the protic solvents ethanol and tert-butanol gave
75 and 78% yields of product 3a, respectively (entries 4 and
5). These results show that the progress of the reaction de-
pends on the nature of the solvent. Fortunately, an aqueous
medium not only afforded a higher yield (84%), but also re-
duced the reaction time from 3 hours to 1 (entry 6). To our
Table 2 Screening of the Solvent and Temperature in a Copper-Cata-
lyzed Azide–Alkyne Huisgen 1,3-Dipolar Cycloadditiona
N
CuAl2O4 NPs (mg)
CH2Ph
N
N
+
NaN3
PhCH2Br
Ph
C
CH
+
Ph
1a
2a
3a
Entry
Solvent
Temp (°C)
Time
Yield (%)
1
2
CH3CN
THF
reflux
reflux
reflux
reflux
reflux
80
3 h
3 h
3 h
3 h
3 h
1 h
36
17
22
75
78
84
89
97
98
79
8
3
CH2Cl2
t-BuOH
EtOH
4
5
6
EtOH–H2O (1:1)
7
H2O
H2O
H2O
H2O
H2O
80
45 min
8c
9d
10e
11f
90
45 min
45 min
45 min
45 min
90
90
90
a Reaction conditions: benzyl bromide (1 mmol), ethynylbenzene (1.1
mmol), NaN3 (1.2 mmol), CuAl2O4 (5.0 mg), solvent (3 mL).
b Isolated yield.
c Optimal conditions.
d With 10 mg of catalyst.
e With 2.5 mg of catalyst.
f With no catalyst.
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–G

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D. Khalili et al.
Letter
Synlett
Table 3 One-Pot CuAl2O4 NPs-Catalyzed Synthesis of 1,2,3-Triazoles from Halidesa
N
R2
CuAl2O4 NPs (5 mg)
H2O, 90 °C
N
N
R2X
R1
C
CH
NaN3
+
+
R1
1
2
3
N
N
N
N
N
N
N
N
N
F
CN
3a, 95%,b 45 min; X = Br
89%, 1.5 h; X = Cl
3b, 87%, 1.5 h; X = Br
80%, 3 h; X = Cl
3c, 92%, 1 h; X = Cl
N
N
N
N
N
N
N
N
N
F
NO2
3d, 83%, 1.5 h; X = Br
3e, 85%, 1 h; X = Br
3f, 96%, 2.5 h; X = Br
76%, 4 h; X = Cl
N
N
N
N
N
N
N
N
N
3g, 95%,c 1 h; X = Br
89%, 1 h; X = Cl
3h, 85%, 2.5 h; X = Br
3i, 83%, 2.5 h; X = Br
79%, 3.5 h; X = Clc
N
N
N
N
N
N
N
N
N
O
O
CN
3j, 81%, 3 h; X = Br
3k, 94%, 1.5 h; X = Br
3l, 89%, 1.5 h; X = Br
N
N
N
N
N
N
N
N
N
F
O
O
O
CN
3m, 90%, 1.5 h; X = Br
3n, 94%, 2 h; X = Br
3o, 94%, 2 h; X = Br
N
N
N
N
N
N
N
N
N
F
O
O
O
F
3p, 95%, 2 h; X = Br
90%, 2 h; X = Cl
3q, 86%, 2 h; X = Br
3r, 88%, 1.5 h; X = Br
83%, 2 h; X = Cl
N
N
N
N
N
N
HO
3s, 79%, 3 h; X = Br
74%, 3 h; X = Cl
3t, 87%, 2 h; X = Br
84%, 2 h; X = Cl
a Reaction condition: alkyl or benzylic halide (1 mmol), terminal alkyne (1.1 mmol), NaN3 (1.2 mmol), CuAl2O4 (5.0 mg), H2O (3 mL), 90 °C.
b Isolated yields are reported.
c The reaction was performed in a sealed tube.
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–G

D
D. Khalili et al.
Letter
Synlett
actions (Table 3). Notably, to bypass the difficulties and
dangers associated with the synthesis and handling of or-
ganic azides, these were generated in situ by treating NaN3
with organic halides. Several benzylic or alkyl halides and
terminal alkynes were examined under the optimum con-
ditions, and these gave a wide range of structurally diverse
1,4-disubstituted triazoles. Generally, electron-donating or
electron-withdrawing groups on the benzylic halides had
only slightly effects on the reactivity, and all the reactants
showed acceptable activity. Nevertheless, electron-donat-
ing groups slightly favored the reaction and higher yields
were obtained (3a–f).19 Primary and secondary alkyl bro-
mides or chlorides were also used in the nucleophilic sub-
stitution followed by 1,3-dipolar cycloaddition to give prod-
ucts 3g–j. Various terminal aliphatic alkynes, such as 1-
benzyl-4-(prop-2-yn-1-yloxy)benzene and 1-(prop-2-yn-
1-yloxy)naphthalene also reacted with high efficiency in
the presence of only 5.0 mg of CuAl2O4 to give products 3k–
r. Attempts to use simple aliphatic alkynes as substrates
were successful and gave the desired products 3s and 3t in
good yields.
To examine the possibility of broadening the scope of
the method, we examined the replacement of halides with
epoxides to give -hydroxy-1,2,3-triazoles. The catalytic
performance of the CuAl2O4 nanoparticles was tested under
the same optimized conditions that were used in the syn-
thesis of the 1,4-disubstituted 1,2,3-triazoles. As shown in
Table 4,[20 several epoxides were tolerated and gave the de-
sired products 5a–j in good to excellent yields.
Notably, the ring-opening of the epoxide occurred pref-
erentially depending on the presence of an alkyl or aryl
group at the position  to the oxygen, so that the regioselec-
tive reaction gave two types of product. In this context, the
use of styrene oxide as a precursor gave the primary -hy-
droxy triazole 5a in excellent yield. An aliphatic epoxide
gave the target product 5b with equal reactivity to aromatic
epoxides, but with the opposite regioselectivity. The reac-
tion conditions were found to tolerate sterically more-hin-
Table 4 Synthesis of 1,4-Disubstituted -Hydroxy-1,2,3-triazoles Catalyzed by Spinel CuAl2O4 NPs
R2
O
N
R
CuAl2O4 NPs (5 mg)
H2O, 90 °C
N
R1
C
CH
N
N
N
N
NaN3
OH
+
+
OH
+
R2
R2
R1
R1
1
4
R2 = aryl
2 = alkyl
5
OH
N
N
N
N
N
N
N
N
N
HO
HO
5a, 94%,b 1 h
5b, 91%, 1.5 h
5c, 90%, 2.5 h
N
N
N
N
N
N
N
N
N
O
O
O
HO
HO
HO
5d, 89%, 2 h
5e, 84%, 3 h
5f, 92%, 3 h
N
OH
N
N
N
N
N
N
O
O
N
N
HO
HO
O
O
O
5g, 83%, 2 h
5h, 87%, 2 h
5i, 86%, 2 h
OH
N
N
N
HO
5j, 80%, 2 h
a Reaction condition: epoxide (1 mmol), terminal alkyne (1.1 mmol), sodium azide (1.2 mmol), CuAl2O4 (5.0 mg) in water (3 ml) at 90 °C.
b Isolated yields are reported.
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–G

E
D. Khalili et al.
Letter
Synlett
dered bicyclic epoxide, such as cyclohexene oxide, which
gave the N-cyclohexyltriazole 5c in 90% isolated yield. The
current procedure was also found to be effective for 2-phe-
noxyoxirane, 2-butoxyoxirane, and 2-allyloxyoxirane,
which gave high yields of the corresponding target products
5d–f, with the same regioselectivity pattern as that of al-
kyl-substituted oxiranes. Moreover, replacement of ethyn-
ylbenzene by nonactivated aliphatic terminal alkynes in-
corporating a 4-benzylphenoxy or 2-naphthyloxy motif
gave the corresponding products 5g–i in good to high
yields. The reaction of 2-methyl-3-butyn-2-ol as a simple
aliphatic alkyne gave the triazole 5j in 80% yield.
From the industrial and environmental viewpoints, the
stability and reusability of catalyst systems are important
features. We therefore used our model reaction (Table 1) to
examine the recyclability of the catalyst system. After each
cycle, the reaction mixture was filtered to separate the cat-
alyst, which was washed with H2O and EtOH then dried in a
vacuum oven at 70 °C for reuse in a subsequent cycle. Nota-
bly, the catalytic system retained its efficiency during six
consecutive cycles (Table 5). After each run, an inductively
coupled plasma analysis was carried out to determine the
amount of catalyst leaching. As shown in Table 5, only neg-
ligible amounts of copper leached from the catalyst surface
during each cycle.
Figure 1 High-resolution narrow X-ray photoelectron spectra (XPS) for
(a) fresh CuAl2O4, and (b) CuAl2O4 treated with sodium azide
A deconvolution of the Cu 2p envelop of the catalyst
treated with NaN3 showed that Cu2+ and Cu+ accounted for
44% and 56% of copper species, respectively. As proven by
XPS analysis, after the generation of Cu+ species, the CuAAC
proceeds according to a reaction mechanism proposed pre-
viously by Sharpless and co-workers (Scheme 1).24
Table 5 Recovery Studies in the Model Reaction (Table 2, Entry 8) Cat-
alyzed by the Same Recovered Spinel CuAl2O4 NPs
Cu(II)Al2O4
Run
1
2
3
4
5
6
N
R2
N
N
NaN3
R1
CH
Yield of 3a (%)
Cu leaching (%)
95
95
94
93
92
89
R1
Cu (I)
0.09
0.16
0.18
0.21
0.22
0.31
N
R2
N
N
R1
C
Cu
A TEM image of the recovered catalyst after the sixth re-
action run indicated that the CuAl2O4 NPs had agglomerat-
ed to form large clusters (see SI, Figure 7). We surmised
that, in the catalytic cycle, NaN3 can change the valence
state of Cu in CuAl2O4 and that this might be responsible for
the observed activity.21,22 To verify this hypothesis and to
gain insight into the possible reaction mechanism, we used
XPS to investigate the oxidation state of the Cu in the fresh
catalyst (see SI, Figure 5) and the CuAl2O4 catalyst treated
with sodium azide. The Cu 2p core-level spectrum (Figure
1a) showed two main peaks at 934.6 and 953.1 eV, which
were assigned to Cu 2p3/2 and Cu 2p1/2, respectively. This re-
sult confirmed the presence of Cu (II) (see SI). As shown in
Figure 1b, when CuAl2O4 was treated with sodium azide, in
addition to the binding energy peaks at 934.8 and 953.0 eV,
two additional sets of binding energy peaks at 932.7 and
954.3 eV were also observed, which clearly indicated that
Cu2+ was partially reduced to Cu+.21,23
R1
Cu
N
N
R2
NaN3
R2-X
N
N
N
C
R2
R1
N
R2
N
N
N
Cu
C
R1
Cu
Scheme 1 The proposed reaction mechanism
In summary, CuAl2O4, as a heterogeneous catalyst, effec-
tively induced multicomponent one-pot reactions of sodi-
um azide with terminal aromatic or aliphatic alkynes and
halides or epoxides to give 1,4-disubstituted 1,2,3-triazoles.
The reactions proceeded in water, an acceptable green sol-
vent, without any additives, and a wide range of structural-
ly diverse precursors could be used under the optimized
conditions. This CuAAC reaction involves the generation of
organic azides in situ by using low-cost sodium azide,
which avoids the need to isolate hazardous organic azides,
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–G

F
D. Khalili et al.
Letter
Synlett
reduces waste generation, and simplifies operational proce-
dures. The recovered catalyst showed a high activity over
six experimental runs.
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Funding Information
Financial support from the Shiraz University research council is grate-
fully acknowledged.
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i
ra
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U
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7
G
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Acknowledgment
The authors thank Mr. Mehdi Koohgard for his kind assistance.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690719.
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(20) 1,2,3-Triazoles; General Procedure
In a 10 mL round-bottomed flask, the alkyl halide or epoxide (1
mmol), terminal alkyne (1.1 mmol), and NaN3 (1.2 mmol) were
mixed and stirred in H2O (3 mL) in the presence of the CuAl2O4
catalyst (0.005g) at 90 °C. When the reaction was complete
(TLC; hexane–EtOAc), the catalyst was collected by simple fil-
tration. The filtrate was diluted with H2O (5 mL) and extracted
with EtOAc (3 × 10 mL). The combined organic phases were
washed with brine, dried (Na2SO4), and concentrated under
reduced pressure. The resulting residue was purified by column
chromatography (silica gel, hexane–EtOAc).
4-({4-[(4-Benzylphenoxy)methyl]-1H-1,2,3-triazol-1-
yl}methyl)benzonitrile (3l)
Yellow solid; yield: 372 mg (89%); mp 63–65 °C. IR (KBr): 3031,
2923, 2360, 2240, 1612, 1512, 1458, 1334, 1234, 1110, 1002,
833, 725 cm–1. 1H NMR (250 MHz, CDCl3):  = 4.93 (s, 2 H), 5.58
(s, 2 H), 5.68 (s, 2 H), 6.69 (dd, J = 7.5, 2.5 Hz, 2 H), 6.88 (dd, J =
10.1, 5.4 Hz, 2 H), 7.27–7.34 (m, 5 H), 7.57 (dd, J = 7.5, 2.5 Hz, 2
H), 7.64 (dd, J = 7.5, 2.5 Hz, 2 H), 7.75 (s, 1 H). 13C NMR (101
MHz, CDCl3):  = 41.09, 53.37, 58.25, 112.31, 114.80, 123.16,
126.13, 128.20, 128.86, 130.00, 130.16, 132.87, 134.13, 135.04,
139.87, 141.46, 145.08, 156.55.
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Org. Chem. 2015, 4, 943. (b) Chavan, P. V.; Charate, S. P.; Desai, U.
V.; Rode, C. V.; Wadgaonkar, P. P. ChemistrySelect 2019, 4, 7144.
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4, 7211. (d) Bahsis, L.; Ben El Ayouchia, H.; Anane, H.; Pascual-
Alvarez, A.; De Munno, G.; Julve, M.; Stiriba, S. E. Appl.
4-[(4-Benzylphenoxy)methyl]-1-(3-fluorobenzyl)-1H-1,2,3-
triazole (3m)
Yellow solid; yield: 369 mg (90%); mp 59–61 °C. IR (KBr): 3070,
2916, 2353, 1697, 1512, 1450, 1250, 1049, 732, 694, 594 cm–1
.
1H NMR (250 MHz, CDCl3):  = 3.82 (s, 2 H), 5.07 (s, 2 H), 5.40 (s,
2 H), 6.65 (dd, J = 5.3, 2.5 Hz, 1 H), 6.84–6.95 (m, 3 H), 6.97–7.02
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–G

G
D. Khalili et al.
Letter
Synlett
(m, 3 H), 7.06–7.11 (m, 4 H), 7.14–7.17 (m, 2 H), 7.45 (s, 1 H). 13
C
CDCl3):  = 41.11, 61.99, 64.77, 67.30, 114.83, 123.76, 126.12,
127.25, 128.54, 128.90, 128.96, 129.14, 130.02, 134.04, 136.08,
141.50, 144.05, 156.66.
NMR (101 MHz, CDCl3):  = 41.14, 53.32, 62.00, 114.71–115.80
(m, 2 C), 126.18, 128.61, 128.97, 130.08, 130.90, 134.07, 137.33,
141.61, 144.68, 156.76, 161.73–164.19 (d, J = 248.5 Hz, 1 C).
2-{4-[(4-Benzylphenoxy)methyl]-1H-1,2,3-triazol-1-yl}-1-
phenylethanol (5g)
(21) Mohammed, S.; Padala, A. K.; Dar, B. A.; Singh, B.; Sreedhar, B.;
Vishwakarma, R. A.; Bharate, S. B. Tetrahedron 2012, 68, 8156.
(22) Kuang, G.-C.; Michaels, H. A.; Simmons, J. T.; Clark, R. J.; Zhu, L. J.
Org. Chem. 2010, 75, 6540.
(23) Li, J.; Ren, Y.; Ji, F.; Lai, B. Chem. Eng. J. (Amsterdam, Neth.) 2017,
324, 63.
White solid; yield: 351 mg (83%); mp 64–66 °C. IR (KBr): 3309,
3062, 2916, 2360, 2245, 2098, 1951, 1890, 1604, 1504, 1450,
1342, 1242, 1049, 910, 840 cm–1 1H NMR (250 MHz, CDCl3):
.
 = 3.89–3.93 (m, 2 H), 4.10–4.22 (m, 1 H), 4.49–4.64 (m, 1 H),
5.13–5.15 (m, 2 H), 5.57–5.65 (m, 1 H), 6.84–6.90 (m, 2 H),
7.16–7.35 (m, 12 H), 7.53–7.56 (m, 1 H). 13C NMR (101 MHz,
(24) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem. Int. Ed. 2002, 41, 2596.
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–G