Copper/HP20: Novel and polymer-supported copper catalyst for huisgen cycloaddition

Article abstract of DOI:10.3987/COM-08-S(F)56

A polymer-supported copper catalyst (Cu/HP20) is easily prepared in water and effectively catalyzed the Huisgen cycloaddition between azides and terminal alkynes.

Full text of DOI:10.3987/COM-08-S(F)56

HETEROCYCLES, Vol. 77, No. 1, 2009
521
HETEROCYCLES, Vol. 77, No. 1, 2009, pp. 521- 532. © The Japan Institute of Heterocyclic Chemistry
Received, 23rd July, 2008, Accepted, 27th August, 2008, Published online, 28th August, 2008.
DOI: 10.3987/COM-08-S(F)56
COPPER/HP20: NOVEL AND POLYMER-SUPPORTED COPPER
CATALYST FOR HUISGEN CYCLOADDITION
Yoshiaki Kitamura,1,2 Kazumi Taniguchi,1 Tomohiro Maegawa,1 Yasunari
Monguchi,1 Yukio Kitade,2-4 and Hironao Sajiki*1,3
1
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 5-6-1,
Mitahora-higashi, Gifu 502-8585, Japan. E-mail address: sajiki@gifu-pu.ac.jp
2
Laboratory of Biomolecular Science, Faculty of Engineering, Gifu University,
1-1, Yanagido, Gifu 501-1193, Japan
3
Center for Advanced Drug Research, Gifu University, 1-1, Yanagido, Gifu
501-1193, Japan
4 United Graduate School of Drug Discovery and Medicinal Information Sciences,
Gifu University, 1-1, Yanagido, Gifu 501-1193, Japan
Abstract – A polymer-supported copper catalyst (Cu/HP20) is easily prepared in
water and effectively catalyzed the Huisgen cycloaddition between azides and
terminal alkynes.
This paper is dedicated to Dr. Keiichiro Fukumoto, Professor Emeritus at Tohoku
University and editor of Heterocycles for the occasion of his 75th birthday.
INTRODUCTION
Recently, heterogeneous catalysts have attracted much attention due to the increasing global momentum
for the development of environmentally-friendly reactions in terms of green chemistry. Activated carbon,
polymers, alumina, silica-gel, zeolites and clay are usually used as the support of a heterogeneous catalyst.
Activated carbon is a useful and versatile support, although the catalyst activity of activated
carbon-supported catalysts is often and subtly different depending on the production lot because it is a
natural material. Therefore, various catalysts supported by synthetic polymers have been investigated.1
Copper plays a remarkable role as a catalyst in various reactions, and many homogeneous copper
catalysts are well known,2 while quite a few heterogeneous catalysts are reported in the literature.3,4 For
example, Girard et al. recently developed a heterogeneous catalyst that relies on chelation to potentially

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HETEROCYCLES, Vol. 77, No. 1, 2009
labile copper using a polystyryl-based benzylic amine polymer,3 and Lipshutz et al. reported an activated
carbon-supported copper catalyst (Cu/C).4 In this article, we report the preparation of a polystyrene
polymer supported novel copper catalyst (Diaion HP20: commercially available from Mitsubishi
Chemical Corporation), Cu/HP20, and its evaluation as a catalyst for the Huisgen cycloaddition reaction
between azides and terminal alkynes.
RESULTS AND DISCUSSION
Preparation of 1% Cu/HP20: We followed the preparation method of Cu/C developed by Lipshutz et al.4
A suspension of Diaion HP20 in a Cu(NO3)2 aqueous solution was sonicated for 2 h and then filtered.
Subsequently, the resulting Cu/HP20 was washed with toluene and dried under vacuum to produce
approximately 1% Cu/HP20 (See Experimental for the determination of the Cu content in the Cu/HP20).
To investigate the catalyst activity of the 1% Cu/HP20, the Huisgen cycloaddition reaction was carried
out. It is well known that the reaction rate of the Huisgen cycloaddition was dramatically accelerated in
the presence of a copper catalyst and stoichiometric amount of Et3N.4 Thus we examined the
cycloaddition of benzylazide (1a) and 1.1 equiv. of 3-methyl-1-butyn-3-ol (2a) in the presence of 1.0
mol% Cu/HP20 and 1.1 equiv. of Et3N at room temperature. The cycloaddition was completed in toluene
within 6 h and provided [2-(1-benzyl-1H-1,2,3-triazol-4-yl)propane-2-ol] (3a) in 98% yield as the sole
product (Scheme 1).
N
1% Cu/HP20 (1.0 mol%)
Et3N (1.1 equiv)
N
OH
N
N3
+
toluene, Ar, rt, 6 h
OH
1a
2a
(1.1 equiv)
3a
98%
Scheme 1. Huisgen’s cycloaddition catalyzed by Cu/HP20
To optimize the reaction conditions, several reaction parameters were surveyed (Table 1). The reduction
of the Cu/HP20 dose caused an extended reaction time (Entry 2), and no product was obtained in the
absence of Cu/HP20 (Entry 1). Among the tested solvents (Entries 4-7), hexane and H2O appeared to be
of equal potential to toluene (Entries 4 and 5), while EtOAc and MeOH were found to be less efficient
(Entries 6 and 7). In the absence of Et3N, the Huigen cycloaddition reaction never proceeded (Entry 8).

HETEROCYCLES, Vol. 77, No. 1, 2009
523
Table 1. Optimization of the reaction conditions
N
N
OH
N
N3
1% Cu/HP20, Et3N
solvent, Ar, rt
+
OH
1a
2a
(1.1 equiv)
3a
Entry
1% Cu/HP20 (mol %)
solvent
Time (h)
Yield (%)a
b
1
2
3
4
5
0
toluene
toluene
toluene
hexane
H2O
AcOEt
MeOH
toluene
24
24
6
6
6
24
24
24
―
0.1
1.0
1.0
1.0
1.0
1.0
1.0
100
100
100
100
100
100
6
7
8c
―
b
a The yield was determined based on the 1H NMR analysis. b No reaction. c The reaction was carried out
without Et3N.
We explored the scope and limitations of substrates for the Huisgen cycloaddition reaction under the
optimal conditions (1.0 mol% Cu/HP20 and 1.1 equiv. of Et3N in toluene at room temperature, Tables 2
and 3). As shown in Table 2, a wide range of azide derivatives smoothly reacted with 2a within 24 h
except for Entry 2. In the case of 3,5-dinitrobenzylazide (1b), the reaction could be successfully achieved
by applying heat (60 ˚C) (Entry 2), since the low solubility of 1b in toluene might be the cause of the
difficult cycloaddition reaction at room temperature in this unusual case.
Table 2. Cu/HP20-catalyzed the Huisgen cycloaddition of various azides with 3-methyl-1-butyn-3-ol (2a)
1% Cu/HP20 (1.0 mol%)
Et3N (1.1 equiv)
N
N
OH
R N
R N3
+
OH
toluene, Ar, rt
1a-h
2a
(1.1 equiv)
3a-h
Entry
1
Azide
Time (h)
Product
Yield (%)a
98
N
N
N3
N
6
OH
1a
3a

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O2N
O2N
N
N
N
N3
―c (100)b
2
24 (5)b
OH
NO2
O2N
O2N
1b
3b
N
N
N
N3
F
3
4
5
5
100
97
OH
O2N
3c
1b
1d
N
N
N3
N
MeO
MeO
24
24
OH
3d
N
N
N
N3
OH
90
1e
3e
O
O
N
N
N
6
24
98
N3
OH
1f
3f
N
N
N
N3
7
8
24
24
98
99
OH
1g
3g
3h
N
O
OH
O
N
N
N3
Br
Br
1h
a Isolated yield. b The reaction was carried out at 60 ˚C. c No reaction.
We next attempted to apply the coupling of 4-fluorobenzylazide (1c) with various terminal alkynes (Table
3). A wide range of terminal alkynes smoothly reacted with 1c within 24 h. Remarkably, the coupling
with 3-methyl-1-butyn-3-ol (2a) and 2-ethynylpyridine (2e) were completed within 5 h and 3 h,
respectively (Entries 1 and 5). In the case of 2a or 2-ethynylpyridine (2e), the coordination of the oxygen
or nitrogen atom of the alkyne to the Cu metal facilitated the approach of Cu species to the adjacent C-C

HETEROCYCLES, Vol. 77, No. 1, 2009
525
triple bond. In addition, the cycloaddition of 2a was completed within 0.5 h by applying heat (60 ˚C),
while the same reaction could be completed within 5 h at room temperature (Entry 1).
Table 3. Cu/HP20-catalyzed Huisgen’s cycloaddition of 4-fluorobenzylazide (1c) with various alkynes
1% Cu/HP20 (1.0 mol%)
Et3N (1.1 equiv)
N
N
N3
N
R
+
R
F
toluene, Ar, rt
F
1c
2a-f
(1.1 equiv)
3c, 3i-m
Entry
1
Alkyne
Time (h)
Product
Yield (%)a
N
OH
N
N
5 (0.5)b
100 (100)b
F
OH
2a
3c
N
N
N
OH
F
2
3
24
79
2b
OH
3i
3j
N
N
N
N
N
N
F
10
24
99
99
2c
N
N
F
F
F
4
2d
3k
N
N
N
N
N
5
6
3
100
90
2e
3l
N
TMS
2f
24
TMS
3m
a Isolated yield. b The reaction was carried out at 60 ˚C.

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HETEROCYCLES, Vol. 77, No. 1, 2009
The reusability of the heterogeneous catalyst could offer significant advantages by association with the
cost reduction and the concept of green chemistry. Cu/HP20 could be recovered by only simple filtration
and reused at least two additional reaction cycles without any loss of activity in the present Huisgen
cycloaddition reaction between 4-fluorobenzylazide (1c) and 3-methyl-1-butyn-3-ol (2a) (Table 4).
Table 4. Investigation in the reuse of Cu/HP20
N
1% Cu/HP20 (1.0 mol%)
Et3N (1.1 equiv)
N
OH
N
N3
+
F
F
toluene, rt
OH
1c
2a
3c
(1.1 equiv)
Entry
Catalyst
Time (h)
Yield (%)a
1
2
3
Cu/HP20
5
5
5
100
99
Recycled Cu/HP20 (1 st)
Recycled Cu/HP20 (2 nd)
99
a Isolated yield.
CONCLUSION
In conclusion, we have developed a novel polystyrene polymer-supported catalyst (Cu/HP20) for the
Huisgen cycloaddition. Aliphatic and aromatic azides underwent the Huisgen cycloaddition reaction with
various terminal alkynes in good-to-excellent yields under mild reaction conditions.
EXPERIMENTAL
General Methods. All reactions were carried out under argon unless otherwise noted. Unless otherwise
stated, the commercially obtained materials were used without further purification. Deionized water was
purchased from Wako Pure Chemical Industries, Ltd. HP20 was gifted from the Mitsubishi Chemical Co.
The azides were prepared according to the known procedure. The terminal alkynes were purchased from
Tokyo Chemical Industry Co., Ltd. Et3N and the solvents were purchased from Nacalai Tasque, Inc. or
1
Wako Pure Chemical Industries, Ltd. The H and 13C NMR spectra were recorded by a JEOL JNM
1
EX-400 or JEOL JNM AL-400 spectrometer (400 MHz for H NMR and 100 MHz for 13C NMR).
Chemical shifts (δ) are expressed in ppm and internally referenced (0.00 ppm for tetramethylsilane
(TMS)-CDCl3 and 2.49 ppm for DMSO-d6 for 1H NMR and 77.0 ppm for CDCl3, 39.5 ppm for DMSO-d6
for 13C NMR). The EI mass spectra were obtained using a JEOL JMS-SX102A instrument. The elemental
analyses were performed by a YANACO MT-5 instrument. The flash column chromatography was

HETEROCYCLES, Vol. 77, No. 1, 2009
527
performed using Kanto Chemical Co., Inc. silica gel 60N, spherical neutral (63-210 µm).
Preparation of 1% Cu/HP20: Diaion HP20 (10.0 g) was suspended in an aqueous solution of Cu(NO3)2
·3H2O (Wako Pure Chemical Industries, Ltd., 1.91 g, 7.9 mmol) in deionized water (40 mL) at rt. The
mixture was sonicated [Honda Electronics W-240R (Honda Electronics Co., Ltd., Aichi, Japan)] for 2 h
and the resulting Cu/HP20 was filtered, washed with toluene (20 mL) and dried under vacuum at rt for 12
h to give approximately 1% Cu/HP20 (4.47 g). Commercially available Diaion HP20 contains around
50% water and the resulting Cu/HP20 is nearly anhydrous. Therefore, the copper contents of HP20 was
calculated on the basis of the measurement of the copper absorbance of the aqueous filtrate using an
atomic absorption photometer [Shimadzu AA-6500 (Shimadzu, Kyoto, Japan)].
Synthesis of substrate:
Preparation of aliphatic azides. Under an argon atmosphere, a mixture of an alkylchloride or
alkylbromide (10.0 mmol), sodium azide (30.0 mmol), and DMF (10 mL) was stirred overnight at rt. The
mixture was extracted with AcOEt (50 mL) and H2O (50 mL). The organic layer was washed with brine
(50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column
chromatography on silica gel to give the corresponding azide.
Benzylazide (1a)5: Colorless oil; 1H NMR (CDCl3) δ 7.41–7.31 (m, 5H), 4.34 (s, 2H); 13C NMR (CDCl3)
δ 135.3, 128.8, 128.3, 128.2, 54.8; HRMS (EI) Calcd for C7H7N3 (M+) 133.0640. Found 133.0649.
3,5-Dinitrobenzylazide (1b): Pale yellow solid; mp 50–52 °C. 1H NMR (DMSO-d6) δ 8.76 (s, 1H), 8.65
(s, 2H), 4.82 (s, 2H); 13C NMR (DMSO-d6) δ 148.1, 140.6, 128.5, 117.9, 51.6; HRMS (EI) Calcd for
C7H5N5O4 (M+) 223.0342. Found 223.0348. Anal. Calcd for C7H5N5O4: C, 37.68; H, 2.26; N, 31.38.
Found: C, 37.65; H, 2.41; N, 31.40.
1
4-Fluorobenzylazide (1c)6: Colorless oil; H NMR (CDCl3) δ 7.31–7.27 (m, 2H), 7.09–7.04 (m, 2H),
4.31 (s, 2H); 13C NMR (CDCl3) δ 162.6 (d, J = 247.7 Hz), 131.2 (d, J = 3.3 Hz), 130.0 (d, J = 8.2 Hz),
115.7 (d, J = 21.4 Hz), 54.0; HRMS (EI) Calcd for C7H6N3F (M+) 151.0546. Found 151.0540.
4-Methoxybenzylazide (1d)7: Colorless oil; 1H NMR (CDCl3) δ 7.25 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8
Hz, 2H), 4.27 (s, 2H), 3.82 (s, 3H); 13C NMR (CDCl3) δ 159.6, 129.7, 127.4, 114.2, 55.2, 54.3; HRMS
(EI) Calcd for C8H9N3O (M+) 163.0746. Found 163.0750.
Phenylpropylazide (1g)8: Colorless oil; 1H NMR (CDCl3) δ 7.32–7.28 (m, 2H), 7.22–7.18 (m, 2H), 3.29
(t, J = 6.8 Hz, 2H), 2.71 (t, J = 6.8 Hz, 2H), 1.92 (quint, J = 6.8 Hz, 2H); 13C NMR (CDCl3) δ 140.8,
128.5, 128.4, 126.1, 50.6, 32.7, 30.4
4-Azido-4’-bromobutylphenone (1h)9: Yellow oil; 1H NMR (CDCl3) δ 7.83 (d, J = 7.2 Hz, 2H), 7.62 (d,
J = 7.2 Hz, 2H), 3.42 (t, J = 6.4 Hz, 2H), 3.05 (t, J = 7.0 Hz, 2H), 2.07-2.00 (m, 2H); 13C NMR (CDCl3) δ

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HETEROCYCLES, Vol. 77, No. 1, 2009
197.8, 135.4, 131.9, 129.5, 128.3, 50.7, 35.1, 25.3; HRMS (EI) Calcd for C10H10BrN3O (M+) 267.0007.
Found 267.0019
Preparation of aromatic azides. To a solution of an arylamine (10.0 mmol) in 10% HCl (15 mL) was
added a solution of sodium nitrite (0.690 g, 10.0 mmol) in water (3 mL) at 0–5°C with vigorous stirring.
The mixture was kept below 5 °C for 30 min and then a solution of sodium azide (0.72 g, 11.0 mmol) in
water (15 mL) was dropwise added while the temperature was kept below 5 °C. After being stirred for 1 h,
the mixture was warmed to rt and extracted with AcOEt (50 mL) and H2O (50 mL). The organic layer
was washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified
by flash column chromatography on silica gel to give the corresponding azide.
1
Phenylazide (1e)10: Colorless oil; H NMR (CDCl3) δ7.35 (t, J = 7.6 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H),
7.03 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3) δ 140.0, 129.7, 124.8, 119.0; HRMS (EI) Calcd for C6H5N3
(M+) 119.0484. Found 119.0487.
4-Benzyoylphenylazide (1f)11: Pale yellow solid; 1H NMR (CDCl3) δ 7.82 (d, J = 7.6 Hz, 2H), 7.75 (d, J
= 8.0 Hz, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H); 13C NMR
(CDCl3) δ 195.0, 144.3, 137.4, 133.9, 132.2, 131.9, 129.7, 128.2, 118.6; HRMS (EI) Calcd for C13H9N3O
(M+) 223.0746. Found 223.0751.
Experiment for the determination of the regiochemistry. Under an argon atmosphere, a mixture of a
benzylazide (650 mg, 5 mmol) and 3-methyl-1-butyn-3-ol (2a, 540 μL, 5.5 mmol) in DMF (5 mL) was
stirred at 80 °C. After being stirred for 72 h, the mixture was extracted with AcOEt (50 mL) and H2O (50
mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo.
The residue was purified by flash column chromatography on silica gel (CHCl3/MeOH, 20:1) to give
2-(1-benzyl-1H-1,2,3-triazol-4-yl)propan-2-ol (467 mg, 43%) and 2-(1-benzyl-1H-1,2,3-triazol-5-yl)-
propan-2-ol (445 mg, 41%).
2-(1-benzyl-1H-1,2,3-triazol-4-yl)propan-2-ol (3a)12: Colorless solid; 1H NMR (CDCl3) δ 7.36 (s, 1H),
7.35-7.33 (m, 3H), 7.29-7.27 (m, 2H), 5.46 (s, 2H), 1.61 (s, 6H); 13C NMR (CDCl3) δ 156.0, 134.6, 129.0,
128.6, 128.0, 119.1, 68.4, 54.0, 30.3; HRMS (EI) Calcd for C12H15N3O (M+) 217.1215. Found 217.1221.
2-(1-benzyl-1H-1,2,3-triazol-5-yl)propan-2-ol13: Colorless solid; 1H NMR (CDCl3) δ 7.27-7.21 (m, 3H),
7.20-7.17 (m, 3H), 5.88 (s, 2H), 1.58 (s, 6H); 13C NMR (CDCl3) δ 143.6, 136.4,130.6, 128.7, 128.2, 128.0,
127.6, 67.6, 52.8, 30.7; HRMS (EI) Calcd for C12H15N3O (M+) 217.1215. Found 217.1221.
General procedure for Huisgen cycloaddition in a solvent system. To a test tube with a stir bar were
added the azide (1.0 mmol), terminal alkyne (1.1 mmol), Et3N (152 μL, 1.1 mmol), 1% Cu/HP20 (63.5

HETEROCYCLES, Vol. 77, No. 1, 2009
529
mg, 10 μmol), and toluene (1 mL), and then the system was sealed with a septum. The air inside was
replaced with argon (balloon) by three vacuum/argon cycles and the mixture was stirred at rt. After a
certain period, the mixture was diluted with H2O (10 mL) and EtOAc (10 mL), and passed through a filter
paper. The filtrate was separated into two layers and the aqueous layer was extracted with EtOAc (2 × 10
mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, and concentrated
in vacuo. The residue was purified by flash column chromatography on silica gel to give the
corresponding 1,4-triazole.
2-[1-(3,5-Dinitrobenzyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3b): Pale yellow solid; mp 117–119 °C.
1H NMR (DMSO-d6) δ 8.79 (s, 1H), 8.65 (s, 2H), 8.09 (s, 1H), 5.86 (s, 2H), 5.16 (s, 1H), 1.44 (s, 6H); 13C
NMR (DMSO-d6) δ 156.4, 148.2, 140.1, 128.9, 121.2, 118.4, 67.1, 50.9, 30.7; HRMS (EI) Calcd for
C12H13N5O5 (M+) 307.0917. Found 307.0910. Anal. Calcd for C12H13N5O5: C, 46.91; H, 4.26; N, 22.79.
Found: C, 46.33; H, 4.04; N, 22.20.
1
2-[1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3c): Pale brown solid; mp 74–76 °C. H
NMR (CDCl3) δ 7.36 (s, 1H), 7.27 (dd, J = 8.6 Hz, 5.4 Hz, 2H), 7.06 (t, J = 8.6 Hz, 2H), 5.46 (s, 2H),
1.61 (s, 6H); 13C NMR (CDCl3) δ 162.8 (d, J = 247.0 Hz), 156.1, 130.5, 130.0 (d, J = 8.2 Hz), 118.9,
116.0 (d, J = 21.4 Hz), 68.5, 53.3, 30.4; HRMS (EI) Calcd for C12H15N3OF (M+) 236.1199. Found
236.1205. Anal. Calcd for C12H15N3OF: C, 61.26; H, 6.00; N, 17.86. Found: C, 61.11; H, 5.90; N, 17.63.
2-[1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3d): Yellow solid; mp 86–88 °C. 1H NMR
(CDCl3) δ 7.30 (s, 1H), 7.23 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 5.43 (s, 2H), 3.81 (s, 3H), 1.60
(s, 6H); 13C NMR (CDCl3) δ 159.9, 155.9, 129.7, 126.5, 118.7, 114.4, 68.4, 55.3, 53.6, 30.4; HRMS
(EI) Calcd for C13H17N3O2 (M+) 247.1321. Found 247.1313. Anal. Calcd for C13H17N3O2: C, 63.14; H,
6.93; N, 16.99. Found: C, 62.81; H, 7.00; N, 16.83.
2-(1-Phenyl-1H-1,2,3-triazol-4-yl)propan-2-ol (3e): Yellow solid; mp 69–71 °C. 1H NMR (CDCl3) δ
7.95 (s, 1H), 7.72 (d, J = 7.8 Hz, 2H), 7.50 (t, J = 7.8 Hz, 2H), 7.42 (t, J = 7.8 Hz, 1H), 1.72 (s, 6H); 13C
NMR (CDCl3) δ 156.5, 136.8, 129.4, 128.4, 120.2, 117.8, 68.3, 30.3; HRMS (EI) Calcd for C11H13N3O
(M+) 203.1059. Found 203.1063. Anal. Calcd for C11H13N3O: C, 65.01; H, 6.45; N, 20.68. Found: C,
65.03; H, 6.47; N, 20.30.
{4-[4-(2-Hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl]phenyl}phenylmethanone (3f): Pale brown
solid; mp 142–144 °C. 1H NMR (CDCl3) δ 8.03 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H),
7.81 (d, J = 7.8 Hz, 2H), 7.63 (t, J = 7.8 Hz, 1H), 7.52 (t, J = 7.8 Hz, 2H), 1.73 (s, 6H); 13C NMR (CDCl3)
δ 195.2, 139.7, 137.3, 137.0, 132.8, 131.7, 129.9, 128.5, 119.8, 117.4, 68.7, 30.4; HRMS (EI) Calcd for
C18H17N3O2 (M+) 307.1321. Found 307.1317. Anal. Calcd for C18H17N3O2: C, 70.34; H, 5.58; N, 13.67.
Found: C, 69.27; H, 5.42; N, 13.30.

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HETEROCYCLES, Vol. 77, No. 1, 2009
2-[1-(3-Phenylpropyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3g): Yellow oil; 1H NMR (CDCl3) δ 7.45 (s,
1H), 7.28 (t, J = 8.2 Hz, 2H), 7.19 (t, J = 8.2 Hz, 1H), 7.15 (d, J = 8.2 Hz, 2H), 4.29 (t, J = 8.2 Hz, 2H),
2.64 (t, J = 8.2 Hz, 2H), 2.21 (quint, J = 8.2 Hz, 2H), 1.63 (s, 6H); 13C NMR (CDCl3) δ 155.8, 140.1,
128.5, 128.3, 126.2, 119.1, 68.3, 49.4, 32.4, 31.5, 30.4; HRMS (EI) Calcd for C14H19N3O (M+) 245.1528.
Found 245.1524. Anal. Calcd for C14H19N3O: C, 68.54; H, 7.81; N, 17.13. Found: C, 68.01; H, 8.03; N,
16.91.
1-(4-Bromophenyl)-4-[4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl]butan-1-one (3h): Colorless
solid; mp 126–128 °C. 1H NMR (CDCl3) δ 7.78 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H), 7.49 (s, 1H),
4.46 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 6.8 Hz, 2H), 2.34 (t, J = 6.8 Hz, 2H), 1.63 (s, 6H); 13C NMR (CDCl3)
δ 197.5, 155.8, 135.1, 132.0, 129.5, 128.6, 119.2, 100.5, 68.4, 49.2, 34.7, 30.4, 24.4; HRMS (EI) Calcd
for C15H18N3O2Br (M+) 351.0582. Found 351.0575. Anal. Calcd for C15H18N3O2Br: C, 51.15; H, 5.15; N,
11.93. Found: C, 51.27; H, 5.11; N, 11.77.
1
3-[1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]propan-1-ol (3i): Pale yellow solid; mp 45–47 °C. H
NMR (CDCl3) δ 7.41 (s, 1H), 7.25 (dd, J = 8.7 Hz, 5.2 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H), 5.43 (s, 2H),
3.97 (s, 1H), 3.85 (t, J = 6.0 Hz, 1H), 2.89 (t, J = 6.0 Hz, 1H); 13C NMR (CDCl3) δ 163.2 (d, J = 248.6
Hz), 146.4, 131.1 (d, J = 3.3 Hz), 130.4 (d, J = 8.2 Hz), 122.2, 116.4 (d, J = 22.2 Hz), 61.6, 53.7, 29.3;
HRMS (EI) Calcd for C11H12N3OF (M+) 221.0964. Found 221.0973. Anal. Calcd for C11H12N3OF: C,
59.72; H, 5.47; N, 18.99. Found: C, 59.13; H, 5.49; N, 18.63.
1-(4-Fluorobenzyl)-4-phenyl-1H-1,2,3-triazole (3j): Colorless solid; mp 125–127 °C. 1H NMR (CDCl3)
δ 7.79 (d, J = 7.4 Hz, 2H), 7.67, 7.40 (t, J = 7.4 Hz, 2H), 7.33-7.26 (m, 3H), 7.07 (t, J = 8.4 Hz, 2H), 5.54
(s, 2H); 13C NMR (CDCl3) δ 162.6 (d, J = 246.2 Hz), 148.1, 130.5 (d, J = 3.3 Hz), 130.3, 129.8 (d, J = 8.2
Hz), 128.7, 128.1, 125.5, 119.4, 115.9 (d, J = 21.2 Hz), 53.2; HRMS (EI) Calcd for C15H12N3F (M+)
253.1015. Found 253.1009. Anal. Calcd for C15H12N3F: C, 71.13; H, 4.78; N, 16.59. Found: C, 71.15; H,
4.82; N, 16.46.
1
4-Cyclohexenyl-1-(4-fluorobenzyl)-1H-1,2,3-triazole (3k): Colorless solid; mp 97–99 °C. H NMR
(CDCl3) δ 7.30 (s, 1H), 7.25 (dd, J = 8.5 Hz, 5.2 Hz, 2H), 7.05 (t, J = 8.5 Hz, 2H), 6.50 (t, J = 1.9 Hz, 1H),
5.47 (s, 2H), 2.35–2.33 (m, 2H), 2.19–2.17 (m, 2H), 1.75–1.71 (m, 2H), 1.68–1.63 (m, 2H); 13C NMR
(CDCl3) δ 162.7 (d, J = 247.0 Hz), 150.0, 130.8 (d, J = 3.3 Hz), 129.7 (d, J = 8.2 Hz), 127.1, 125.2, 118.0,
116.0 (d, J = 22.2 Hz), 53.2, 26.3, 25.2, 22.4, 22.1; HRMS (EI) Calcd for C15H16N3F (M+) 257.1328.
Found 257.1321. Anal. Calcd for C15H16N3F: C, 70.02; H, 6.27; N, 16.33. Found: C, 70.01; H, 6.23; N,
16.17.
2-[1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]pyridine (3l): Pale brown solid; mp 104–106 °C. 1H NMR
(CDCl3) δ 8.53 (d, J = 5.0 Hz, 1H), 8.16 (d, J = 7.8 Hz, 1H), 8.08 (s, 1H), 7.74 (dd, J = 7.8 Hz, 6.3 Hz,
1H), 7.31 (dd, J = 8.7 Hz, 5.2 Hz, 2H), 7.19 (dd, J = 6.3 Hz, 5.0 Hz, 1H), 7.04 (t, J = 8.7 Hz, 2H), 5.54 (s,

HETEROCYCLES, Vol. 77, No. 1, 2009
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2H); 13C NMR (CDCl3) δ 162.7 (d, J = 247.0 Hz), 149.9, 149.2, 148.6, 136.7, 130.2 (d, J = 3.3 Hz), 130.0
(d, J = 8.2 Hz), 122.7, 121.7, 120.0, 115.9 (d, J = 21.4 Hz), 53.3; HRMS (EI) Calcd for C14H11N4F (M+)
254.0968. Found 254.0962. Anal. Calcd for C14H11N4F: C, 66.13; H, 4.36; N, 22.04. Found: C, 65.96; H,
4.46; N, 21.80.
1-(4-Fluorobenzyl)-4-trimethylsilyl-1H-1,2,3-triazole (3m): Pale yellow solid; mp 59–61 °C. 1H NMR
(CDCl3) δ 7.18 (s, 1H), 6.98 (dd, J = 8.6 Hz, 4.8 Hz, 2H), 6.75 (t, J = 8.8 Hz, 2H), 5.24 (s, 2H), 0.01 (s,
13
9H); C NMR (CDCl3) δ 162.6 (d, J = 248.6 Hz), 147.1, 130.8 (d, J = 3.3 Hz), 129.8 (d, J = 8.1 Hz),
128.6, 115.8 (d, J = 22.2 Hz), 60.2, 52.5; HRMS (EI) Calcd for C12H16N3FSi (M+) 249.1098. Found
249.1093. Anal. Calcd for C12H16N3FSi: C, 57.80; H, 6.47; N, 16.85. Found: C, 57.75; H, 6.32; N, 16.90.
ACKNOWLEDGEMENTS
We thank Mitsubishi Chemical Corporation for a gift of Diaion HP20.
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