An easy access to unsymmetrically substituted 4,4′-bi-1,2,3-triazoles

Article abstract of DOI:10.1016/j.tet.2009.10.078

A convenient synthesis of 4-alkynyl-1,2,3-triazoles and novel unsymmetrically substituted 4,4′-bi-1,2,3-triazole derivatives has been devised starting from easily available 1-trimethylsilyl-1,3-butadiyne. The starting compound was reacted with several azi

Full text of DOI:10.1016/j.tet.2009.10.078

Tetrahedron 65 (2009) 10573–10580
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An easy access to unsymmetrically substituted 4,40-bi-1,2,3-triazoles
*
Vito Fiandanese , Daniela Bottalico, Giuseppe Marchese, Angela Punzi, Francesca Capuzzolo
`
Dipartimento di Chimica, Universita di Bari, via Orabona 4, 70126 Bari, Italy
a r t i c l e i n f o
a b s t r a c t
A convenient synthesis of 4-alkynyl-1,2,3-triazoles and novel unsymmetrically substituted 4,40-bi-1,2,3-
triazole derivatives has been devised starting from easily available 1-trimethylsilyl-1,3-butadiyne. The
starting compound was reacted with several azides, leading to 4-(silylalkynyl)-1,2,3-triazoles, which
were easily transformed into 4-arylalkynyl-1,2,3-triazoles by a Pd catalyzed coupling reaction with aryl
halides, or into novel 4,40-bi-1,2,3-triazole derivatives by a subsequent cyclization reaction with azides.
Ó 2009 Elsevier Ltd. All rights reserved.
Article history:
Received 16 July 2009
Received in revised form 5 October 2009
Accepted 22 October 2009
Available online 25 October 2009
1. Introduction
triazoles, based upon the use of 1-trimethylsilyl-1,3-butadiyne9 as
starting material, via click chemistry. Indeed, up to date, only one
Nitrogen heterocycles, such as 1,2,3-triazoles, have found a wide
range of important applications in the agrochemical, pharmaceu-
tical, polymer, and materials field.1 In addition, several compounds
of the 1,2,3-triazole family have shown a broad spectrum of
biological properties such as antibacterial,2 antiallergic,3 and anti-
HIV activity.4 An important methodology for the synthesis of 1,2,3-
triazoles is based upon the Huisgen cycloaddition using azides and
alkynes.5 However, the high reaction temperatures and the low
regioselectivity are major limitations of the original reactions.
These limitations have been overcome by the introduction of the
copper catalyzed 1,3-dipolar cycloaddition of azides and terminal
alkynes, the so-called ‘click chemistry’, which was pioneered by
Sharpless6 and Meldal.7 It was found that cycloadditions of termi-
nal alkynes with azides catalyzed by Cu(I) can be conducted at
room temperature and are highly regioselective leading exclusively
to 4-substituted-1,2,3-triazoles. In addition, many new catalyst
systems have been reported in recent years and the number of
publications dealing with click chemistry has grown exponentially
over the last few years.8
report described the synthesis of a 4-substituted-1,2,3-triazole
obtained by reaction of the above compound with a complex
azide.14 Moreover, a few and scattered examples of the synthesis of
1,2,3-triazoles were reported, by reaction of a mono-silylated 1,3-
butadiyne8i or of aryl 1,3-butadiynes with benzyl azide.15
2. Results and discussion
We investigated the catalytic activity of various copper salts and
found that compound 1 was easily cyclized with several azides in
the presence of Cu(OAc)2 as a catalyst,8l according to Scheme 1.
N
R-N3
N
N
SiMe3
SiMe3
.
Cu(OAc)2 H2O
H2O, r.t.
R
1
2
Scheme 1.
All reactions were performed in H2O in the presence of
Cu(OAc)2$H2O as a catalyst (20 mol %) at room temperature and the
overall results are reported in Table 1. The reactions of several
azides with compound 1 provided reasonable to good yields (51–
92%) of the 1,4-triazole adducts, regardless of the substituted azide.
Indeed, we employed arylalkyl azides (entries 1–4) also with the
aryl group ortho- or para-iodosubstituted (entries 2 and 3), or
arylazides (entries 5 and 6) and finally alkyl azides (entries 7 and 8).
These results encouraged us to extend the methodology to the
synthesis of more triazole derivatives, starting from compounds 2.
Then, we subjected some mono-silylated compounds 2 to a direct
cross-coupling reaction9 with different aryl iodides, in the presence
of catalytic amounts of Pd(PPh3)4 and AgCl, obtaining various
substituted 4-(arylalkynyl)-1,2,3-triazoles 3 (Scheme 2).
Owing to our continuing interest in the synthesis of novel
structures of biological significance, we recently reported the suc-
cessful applications of our methodology9 to the synthesis of a va-
riety of naturally occurring diacetylenic and polyacetylenic
compounds.10,11 Moreover, more recently, a further application of
our method led to a straightforward synthesis of a variety of het-
erocyclic compounds, with an indole and benzofuran skeleton,
starting from easily available silylated diynes.12,13 On the basis of
these results, we decided to evaluate the possibility of devising an
easy and general approach to more complex 4-substituted-1,2,3-
* Corresponding author. Tel.: þ39 080 5442075; fax: þ39 080 5442075.
E-mail address: fianda@chimica.uniba.it (V. Fiandanese).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.078

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V. Fiandanese et al. / Tetrahedron 65 (2009) 10573–10580
multidentate ligands of transition metals.16,17 We found that, by
Table 1
employing an in situ deprotection and clicking reaction,8a com-
pounds 2 reacted with several azides leading to 4,40-bi-triazole
derivatives 4 (Scheme 3).
Synthesis of 4-trimethylsilylalkynyl-1,2,3-triazoles 2
Entry
1
R–N3
Products 2a, yieldb (%)
N
N
SiMe3
SiMe3
N
N
N
N
R'-N3
N
N
N
N
N
N
N3
SiMe3
CuI, TBAF
amine, THF, r.t.
2a (77)
R
R
R'
4
2
I
N
N
N
I
Scheme 3.
2
3
N3
2b (81)
The reactions were performed in THF, at room temperature, by
employing a Cu(I) copper source and TBAF as in situ desilylating
agent, in the presence of an amine, 1,1,4,7,7-pentamethyldiethylene-
triamine. The overall results are reported in Table 3. In particular, as
representative examples, we subjected compounds 2a and 2g to the
cyclization reaction. Compound 2a was reacted with arylalkyl azides
(entries 1 and 2) and with alkyl azides (entries 3 and 4), whereas
compound 2g was reacted with alkyl and arylalkyl azides (entries 5–
7) and an arylazide (entry 8), obtaining the unsymmetrically
substituted 4,40-bi-triazole derivatives in good yields (52–86%). It is
noteworthy that the same product 4d can be obtained starting from
compound 2a (entry 4) or from compound 2g (entry 5) and that the
ready availability of compounds 2 can provide a wide range of un-
symmetrically substituted 4,40-bi-triazole adducts.
In summary, we have shown that a variety of 4-alkynyl-1,2,3-
triazoles (products 2 and 3) can be easily synthesized via ‘click’
chemistry starting from the easily available compound 1 and, es-
pecially, we have devised a general approach to novel un-
symmetrically substituted 4,40-bi-triazole adducts 4 by simple
sequential cyclization reactions.
I
N
N
I
SiMe3
N
N3
2c (92)
N
N
SiMe3
N
4
N3
2d (83)
N
N
CH3O
SiMe3
N
5
6
7
N3
2e (51)
CH3O
N
I
N
N
I
SiMe3
N3
2f (61)
N
N
N
SiMe3
N3
3. Experimental
3.1. General
2g (80)
N
N
N
Macherey–Nagel silica gel (60, particle size 0.040–0.063 mm) for
column chromatography and Macherey–Nagel aluminum sheets
with silica gel 60 F254 for TLC were used. GC analysis was performed
on a Varian 3900 gas chromatograph equipped with a Supelco
SLBTM-5ms capillary column (30 mꢀ0.25 mm id). GC–mass spec-
trometry analysis was performed on a Shimadzu GCMS-QP5000 gas
SiMe3
N3
8
2h (87)
a
All reactions were carried out in H2O at room temperature for 1–6 h, according
to a general procedure.
b
Yields of purified isolated products.
chromatograph–mass spectrometer equipped with
a Supelco
SLBTM-5ms capillary column (30 mꢀ0.25 mm id). 1H NMR spectra
were recorded in deuterochloroform or DMSO-d6 on a Varian Inova
at 400 MHz.13C NMR spectra were recorded in deuterochloroform or
DMSO-d6 on a Varian Inova at 100.6 MHz. IR spectra were recorded
on a Perkin–Elmer FT-IR Spectrum Bx. Elemental analyses were
recorded on a Carlo Erba EA 1108 elemental analyzer. Melting points
were determined on a Reichert Microscope or on a Stuart Scientific
Melting point apparatus SMP3. Tetrahydrofuran was distilled from
sodium and N,N-dimethylformamide was used as supplied.
Ar-X
Pd(PPh3)4
N
N
N
N
N
N
SiMe3
Ar
AgCl, K2CO3
MeOH, DMF
R
R
2
3
Scheme 2.
Several aryl and p-substituted aryl iodides were employed
(Table 2, entries 2 and 5–8) and also heteroaryl iodides, such as 3-
iodopyridine (entry 1), 2-iodobenzofuran (entry 3), and 2-iodo-
thiophene (entry 4) and functionalized 4-alkynyl-1,2,3-triazoles 3
were obtained in good to high yields (67–86%).
3.2. General procedure for the synthesis of compounds 2
Moreover, in order to demonstrate the high versatility of com-
pound 2, we started to investigate the possibility of performing
a new cyclization reaction, with the aim of obtaining novel un-
symmetrically substituted 4,40-bi-triazole derivatives, compounds,
to the best of our knowledge, never synthesized. Indeed, more
recently, only some symmetrically substituted 4,40-bi-triazole de-
rivatives have been prepared, by copper catalyzed reactions of 1,4-
bis(trimethylsilyl)-1,3-butadiyne16 or 1,3-butadiyne17 with some
azides and these symmetrical adducts have been evaluated as
1-Trimethylsilyl-1,3-butadiyne (1.2 equiv) and azide (1 equiv)
were added at room temperature to a solution (0.10 M) of
Cu(OAc)2$H2O (0.2 equiv) in H2O in a capped flask. The mixture was
stirred at room temperature and, after reaction completion (1–6 h),
was quenched with a saturated aqueous solution of NH4Cl (20 mL)
and extracted with ethyl acetate (3ꢀ30 mL). The organic extracts
were washed with water (3ꢀ20 mL), dried over Na2SO4, and con-
centrated under vacuum. The residue was purified by column
chromatography on silica gel and by crystallization.

V. Fiandanese et al. / Tetrahedron 65 (2009) 10573–10580
10575
Table 2
Synthesis of substituted 4-arylalkynyl-1,2,3-triazoles 3
Entry
1
Compound 2
Ar–I
Products 3a, yieldb (%)
N
N
I
2a
N
N
N
3a (71)
N
N
OCH3
2
3
2a
2d
CH3O
I
N
c
3b (68)
N
N
I
N
O
O
c
3c (75)
N
N
N
I
S
4
5
2d
2d
S
3d (80)
N
N
N
I
I
3e (86)
N
N
N
6
7
2e
CH3O
3f (70)
N
N
CH3
N
2h
2h
CH3
I
c
3g (67)
N
N
N
NO2
8
O2N
I
c
3h (83)
a
Unless otherwise indicated, all reactions were performed in DMF at room temperature for 4–18 h.
Yields of purified isolated products.
Reactions performed at 40 ꢁC for 2–6 h.
b
c
3.2.1. 4-(Trimethylsilylethynyl)-1-benzyl-1H-1,2,3-triazole (2a). Com-
butadiyne (0.113 g, 0.93 mmol) and 2-iodobenzylazide (0.202 g,
0.78 mmol) in accordance with general procedure. Purification by
column chromatography (silica gel, 20% ethyl acetate/petroleum
ether) afforded 0.241 g of compound 2b (81% yield). After crystalli-
zation from ethyl acetate/petroleum ether, compound 2b was
obtained as a light brown solid, mp¼116–117 ꢁC. [Found: C, 44.15; H,
4.28; N, 11.08. C14H16IN3Si requires C, 44.10; H, 4.23; N, 11.02%.] nmax
(KBr) 3147, 2960, 2172, 1457, 1450, 1437, 1424, 1339, 1249, 1222, 1051,
1012, 860, 844, 746; dH (400 MHz, CDCl3) 7.87 (dd, J¼7.9, 0.9 Hz, 1H),
7.64 (s,1H), 7.37–7.30 (m,1H), 7.12 (dd, J¼7.7,1.4 Hz,1H), 7.09–7.02 (m,
1H), 5.60 (s, 2H), 0.22 (s, 9H); dC (100.6 MHz, CDCl3) 139.9,136.7,131.2,
130.6, 129.9, 129.1, 126.4, 98.9, 98.8, 93.4, 58.4, ꢂ0.4; MS m/z 353 (2),
338 (2), 226 (13), 217 (100), 210 (4),196 (12),185 (5),150 (5),108 (12),
91 (22), 90 (47), 89 (24), 73 (38), 63 (10), 59 (14), 53 (11), 43 (31%).
pound 2a was prepared from 1-trimethylsilyl-1,3-butadiyne
(0.220 g, 1.80 mmol) and benzyl azide (0.200 g, 1.50 mmol) in ac-
cordance with general procedure. Purification by column chroma-
tography (silica gel, 20% ethyl acetate/petroleum ether) afforded
0.295 g of compound 2a (77% yield). After crystallization from pe-
troleum ether, compound 2a was obtained as a white solid,
mp¼90–91 ꢁC. [Found: C, 65.90; H, 6.68; N, 16.50. C14H17N3Si re-
quires C, 65.84; H, 6.71; N, 16.45%.] nmax (KBr) 3130, 2959, 2170,
1456, 1333, 1251, 1223, 1052, 854, 836, 756, 718, 704; dH (400 MHz,
CDCl3) 7.52 (s, 1H), 7.37–7.32 (m, 3H), 7.25–7.20 (m, 2H), 5.49 (s,
2H), 0.19 (s, 9H); dC (100.6 MHz, CDCl3) 134.0, 131.3, 129.1, 128.9,
128.1, 126.2, 98.8, 93.4, 54.2, ꢂ0.4; MS m/z 227 (3), 226 (4), 212 (5),
185 (4), 182 (3), 150 (3), 108 (7), 91 (100), 84 (4), 83 (6), 73 (17), 65
(20), 59 (8), 55 (4), 53 (7), 43 (20%).
3.2.3. 4-(Trimethylsilylethynyl)-1-(4-iodobenzyl)-1H-1,2,3-triazole
(2c). Compound 2c was prepared from 1-trimethylsilyl-1,3-buta-
diyne (0.113 g, 0.93 mmol) and 4-iodobenzylazide (0.202 g,
3.2.2. 4-(Trimethylsilylethynyl)-1-(2-iodobenzyl)-1H-1,2,3-triazole
(2b). Compound 2b was prepared from 1-trimethylsilyl-1,3-

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V. Fiandanese et al. / Tetrahedron 65 (2009) 10573–10580
Table 3
Synthesis of unsymmetrically substituted 4,40-bi-1,2,3-triazole derivatives 4
Entry
Compound 2
R0–N3
Products 4a yield,b (%)
N
N
N
N
N
N
1
2a
N3
4a (64)
N
N
N
N
N
N
2
3
4
5
6
2a
2a
2a
2g
2g
N3
4b (65)
N
N
N
N
N
N
N3
4c (75)
N
N
N
N
N
N
N
N3
4d (62)
N
N
N
N
N
N3
4d (86)
N
N
N
N
N
N
N
N3
4e (52)
N
N
N
N
N
7
2g
2g
N3
4f (78)
N
N
N
N
CH3O
N
N
8
N3
4g (66)
OCH3
a
All reactions were carried out in THF at room temperature for 2–4 h.
Yields of isolated purified products.
b
0.78 mmol) in accordance with general procedure. Purification by
column chromatography (silica gel, 20% ethyl acetate/petroleum
ether) afforded 0.273 g of compound 2b (92% yield). After crystal-
lization from ethyl acetate/petroleum ether, compound 2c was
obtained as a light brown solid, mp¼138–140 ꢁC. [Found: C, 44.17;
H, 4.25; N, 11.00. C14H16IN3Si requires C, 44.10; H, 4.23; N, 11.02%.]
nmax (KBr) 3133, 2956, 2165, 1484, 1455, 1423, 1404, 1337, 1275,
1249, 1227, 1051, 1022, 1007, 860, 846, 799, 787, 763, 731; dH
(400 MHz, CDCl3) 7.69 (d, J¼8.2 Hz, 2H), 7.55 (s, 1H), 6.98 (d,
J¼8.2 Hz, 2H), 5.44 (s, 2H), 0.21 (s, 9H); dC (100.6 MHz, CDCl3) 138.3,
133.7, 131.5, 129.8, 126.1, 99.0, 94.7, 93.2, 53.6, ꢂ0.4; MS m/z 353 (8),
338 (3), 226 (3), 217 (100), 196 (12), 150 (5), 136 (2), 108 (16), 90
(45), 89 (25), 83 (9), 73 (28), 63 (8), 59 (13), 53 (9), 43 (28%).
7.17; N, 15.55. C15H19N3Si requires C, 66.87; H, 7.11; N, 15.60%.] nmax
(KBr) 3132, 3027, 2957, 2170, 1454, 1437, 1333, 1249, 1224, 1053,
1027, 863, 846, 763, 752, 717, 704, 696; dH (400 MHz, CDCl3) 7.35 (s,
1H), 7.30–7.20 (m, 3H), 7.08–7.04 (m, 2H), 4.55 (t, J¼7.2 Hz, 2H), 3.17
(t, J¼7.2 Hz, 2H), 0.21 (s, 9H); dC (100.6 MHz, CDCl3) 136.5, 130.6,
128.8, 128.6, 127.1, 126.4, 98.5, 93.5, 51.7, 36.5, ꢂ0.4; MS m/z 241 (1),
240 (3), 226(3), 168 (2), 150 (13), 122 (4), 105 (100), 91 (19), 86 (13),
79 (20), 77 (18), 73 (22), 59 (26), 43 (21%).
3.2.5. 4-(Trimethylsilylethynyl)-1-(4-methoxyphenyl)-1H-1,2,3-tri-
azole (2e). Compound 2e was prepared from 1-trimethylsilyl-1,3-
butadiyne (0.196 g, 1.61 mmol) and 4-methoxyphenylazide (0.200 g,
1.34 mmol) in accordance with general procedure. Purification by
column chromatography (silica gel, 20% ethyl acetate/petroleum
ether) afforded 0.185 g of compound 2e (51% yield). After crystalli-
zation from ethyl acetate/petroleum ether, compound 2e was
obtained as a bronze solid, mp¼126–128 ꢁC. [Found: C, 61.90; H, 6.27;
N, 15.42. C14H17N3OSi requires C, 61.96; H, 6.31; N,15.48%.] nmax (KBr)
3137, 2959, 2166, 1516, 1308, 1255, 1236, 1049, 1035, 863, 842, 832,
760; dH (400 MHz, CDCl3) 7.96 (s, 1H), 7.57 (d, J¼8.8 Hz, 2H), 6.99 (d,
J¼8.8 Hz, 2H), 3.83 (s, 3H), 0.24 (s, 9H); dC (100.6 MHz, CDCl3) 160.0,
131.4,129.8,124.4,122.2,114.8, 99.4, 93.2, 55.6, ꢂ0.4; MS m/z 243 (14),
3.2.4. 4-(Trimethylsilylethynyl)-1-(2-phenylethyl)-1H-1,2,3-triazole
(2d). Compound 2d was prepared from 1-trimethylsilyl-1,3-buta-
diyne (0.299 g, 2.45 mmol) and 2-phenylethylazide (0.300 g,
2.04 mmol) in accordance with general procedure. Purification by
column chromatography (silica gel, 20% ethyl acetate/petroleum
ether) afforded 0.455 g of compound 2d (83% yield). After crystal-
lization from ethyl acetate/petroleum ether, compound 2d was
obtained as a white solid, mp¼101–103 ꢁC. [Found: C, 66.90; H,

V. Fiandanese et al. / Tetrahedron 65 (2009) 10573–10580
10577
228 (100), 213(12), 200(7),198(6),185(5),170 (5),164(5),154(5),121
(4),107 (13), 93(18), 79 (15), 77 (13), 69 (9), 67 (14), 64 (13), 63(11), 59
(9), 55 (11), 53 (16), 43 (45%).
residue was purified by column chromatography on silica gel and
by crystallization.
3.3.1. 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)ethynyl]pyridine (3a). Com-
pound 3a was prepared from 2a (0.200 g, 0.78 mmol) and 3-iodo-
pyridine (0.160 g, 0.78 mmol) and the reaction was performed at
room temperature in accordance with general procedure. Purifi-
cation by column chromatography (silica gel, 40% petroleum ether/
ethyl acetate) afforded 0.144 g of compound 3a (71% yield). After
crystallization from ethyl acetate/petroleum ether, compound 3a
was obtained as a pale yellow solid, mp¼111–113 ꢁC. [Found: C,
73.85; H, 4.60; N, 21.49. C16H12N4 requires C, 73.83; H, 4.65; N,
21.52%.] nmax (KBr) 3081, 3032, 2949, 2230, 1474, 1457, 1407, 1339,
1241,1213,1054,1022, 814, 715, 702; dH (400 MHz, CDCl3) 8.70 (br s,
1H), 8.51 (br s, 1H), 7.74 (dt, J¼7.9, 1.8 Hz, 1H), 7.62 (s, 1H), 7.37–7.31
(m, 3H), 7.27–7.21 (m, 3H), 5.52 (s, 2H); dC (100.6 MHz, CDCl3) 152.1,
149.0, 138.4, 133.9, 130.8, 129.2, 129.0, 128.1, 126.1, 123.1, 119.5, 89.2,
81.8, 54.4; MS m/z 260 (Mþ, 2), 231 (14), 204 (18), 154 (3), 141 (5),
114 (5), 102 (5), 91 (100), 74 (6), 65 (22), 51 (8%).
3.2.6. 4-(Trimethylsilylethynyl)-1-(2-iodophenyl)-1H-1,2,3-triazole
(2f). Compound 2f was prepared from 1-trimethylsilyl-1,3-buta-
diyne (0.300 g, 2.46 mmol) and 2-iodophenylazide (0.502 g,
2.05 mmol) in accordance with general procedure. Purification by
column chromatography (silica gel, 20% ethyl acetate/petroleum
ether) afforded 0.459 g of compound 2f (61% yield). After crystal-
lization from ethyl acetate/petroleum ether, compound 2f was
obtained as a light brown solid, mp¼93–95 ꢁC. [Found: C, 42.48; H,
3.75; N, 11.48. C13H14IN3Si requires C, 42.51; H, 3.84; N, 11.44%.] nmax
(KBr) 3138, 2957, 2899, 2175, 1485, 1247, 1230, 1040, 860, 840, 764;
dH (400 MHz, CDCl3) 7.99 (dd, J¼8.0, 1.2 Hz, 1H), 7.94 (s, 1H), 7.53–
7.47 (m, 1H), 7.40 (dd, J¼8.0, 1.6 Hz, 1H), 7.27–7.21 (m, 1H), 0.26 (s,
9H); dC (100.6 MHz, CDCl3) 140.3, 139.4, 131.7, 130.9, 129.3, 128.1,
127.8, 99.5, 93.7, 93.0, ꢂ0.3; MS m/z 339 (58), 324 (100), 197 (24),
182 (29), 162 (27), 154 (17), 140 (8), 127 (10), 106 (13), 85 (10), 77
(13), 53 (23), 43 (42%).
3.3.2. 4-[(4-Methoxyphenyl)ethynyl]-1-benzyl-1H-1,2,3-triazole
(3b)8i,15. Compound 3b was prepared from 2a (0.142 g, 0.56 mmol)
and 4-methoxyiodobenzene (0.131 g, 0.56 mmol) and the reaction
was performed at 40 ꢁC. Purification by column chromatography
(silica gel, 30% ethyl acetate/petroleum ether) afforded 0.110 g of
compound 3b (68% yield). After crystallization from ethyl acetate/
petroleum ether, compound 3b was obtained as a yellow solid,
mp¼163–166 ꢁC. [Found: C, 74.80; H, 5.28; N, 14.59. C18H15N3O
requires C, 74.72; H, 5.23; N, 14.52%.] nmax (KBr) 3128, 2959, 2929,
2834, 2219, 1605, 1541, 1501, 1456, 1292, 1250, 1227, 1172, 1052,
1027, 834, 817, 709, 700; dH (400 MHz, CDCl3) 7.56 (s, 1H), 7.42 (d,
J¼9.0 Hz, 2H), 7.38–7.32 (m, 3H), 7.28–7.23 (m, 2H), 6.83 (d,
J¼9.0 Hz, 2H), 5.51 (s, 2H), 3.78 (s, 3H); dC (100.6 MHz, CDCl3) 159.9,
134.1, 133.0, 131.7, 129.1, 128.9, 128.1, 125.5, 114.2, 114.0, 92.6, 77.1,
55.2, 54.2; MS m/z 289 (Mþ, 9), 260 (23), 246 (13), 234 (26), 219
(23), 217 (25), 203 (16), 191 (20), 170 (11), 143 (21), 127 (10), 113
(13), 100 (15), 91 (100), 74 (14), 65 (44), 63 (21) 51 (18%).
3.2.7. 4-(Trimethylsilylethynyl)-1-octyl-1H-1,2,3-triazole (2g). Com-
pound 2g was prepared from 1-trimethylsilyl-1,3-butadiyne
(0.284 g, 2.33 mmol) and n-octylazide (0.300 g, 1.94 mmol) in ac-
cordance with general procedure. Purification by column chroma-
tography (silica gel, 20% ethyl acetate/petroleum ether) afforded
0.430 g of compound 2g (80% yield) as a pale yellow oil. [Found: C,
64.90; H, 9.78; N, 15.08. C15H27N3Si requires C, 64.93; H, 9.81; N,
15.14%.] nmax (neat) 3134, 2956, 2927, 2856, 2172, 1458, 1250, 1048,
863, 844, 760; dH (400 MHz, CDCl3) 7.60 (s, 1H), 4.30 (t, J¼7.2 Hz,
2H), 1.89–1.80 (m, 2H), 1.30–1.16 (m, 10H), 0.83 (t, J¼6.8 Hz, 3H),
0.21 (s, 9H); dC (100.6 MHz, CDCl3) 130.8, 126.0, 98.5, 93.6, 50.5,
31.6, 30.1, 29.0, 28.9, 26.3, 22.5, 14.0, ꢂ0.4; MS m/z 277 (Mþ, <1),
262 (2), 234 (2), 207 (4), 192 (3), 178 (4), 176 (4), 165 (13), 164 (12),
150 (73), 137 (20), 122 (36), 109 (11), 107 (14), 86 (23), 73 (48), 59
(43), 57 (27), 55 (26), 43 (100), 41 (81%).
3.2.8. 4-(Trimethylsilylethynyl)-1-decyl-1H-1,2,3-triazole (2h). Com-
pound 2h was prepared from 1-trimethylsilyl-1,3-butadiyne
(0.300 g, 2.46 mmol) and n-decylazide (0.375 g, 2.05 mmol) in ac-
cordance with general procedure. Purification by column chroma-
tography (silica gel, 20% ethyl acetate/petroleum ether) afforded
0.544 g of compound 2h (87% yield) as a pale yellow oil. [Found: C,
66.80; H, 10.28; N, 13.78. C17H31N3Si requires C, 66.83; H, 10.23; N,
13.75%.] nmax (neat) 3134, 2955, 2929, 2854, 2172, 1457, 1436, 1250,
1223, 1047, 861, 843, 760; dH (400 MHz, CDCl3) 7.58 (s, 1H), 4.27 (t,
J¼7.2 Hz, 2H), 1.85–1.73 (m, 2H), 1.27–1.10 (m, 14H), 0.80 (t, J¼6.6 Hz,
3H), 0.17 (s, 9H); dC (100.6 MHz, CDCl3) 130.7, 126.0, 98.3, 93.6, 50.3,
31.7, 30.0, 29.3, 29.2, 29.1, 28.8, 26.2, 22.5, 13.9, ꢂ0.5; MS m/z 290 (2),
262 (2), 235 (2), 234 (2), 220 (2), 204 (3),192 (3),178 (3),166 (11),165
(13), 164 (10), 150 (56), 137 (14), 124 (10), 122 (22), 109 (9), 107 (11),
86 (15), 73 (43), 59 (36), 57 (28), 55 (28), 43 (100), 41 (80%).
3.3.3. 4-(1-Benzofuran-2-ylethynyl)-1-(2-phenylethyl)-1H-1,2,3-tri-
azole (3c). Compound 3c wasprepared from 2d(0.200 g, 0.74 mmol)
and 2-iodobenzofuran (0.181 g, 0.74 mmol) and the reaction was
performed at 40 ꢁC in accordance with general procedure. Purifica-
tion by column chromatography (silica gel, 20% ethyl acetate/petro-
leum ether) afforded 0.173 g of compound 3c (75% yield). After
crystallizationfromethylacetate/petroleumether, compound3cwas
obtained as a pale yellow solid, mp¼118–120 ꢁC. [Found: C, 76.70; H,
4.79; N, 13.38. C20H15N3O requires C, 76.66; H, 4.82; N, 13.41%.] nmax
(KBr): 3116, 2959, 2924, 2227, 1447, 1259, 1100, 1050, 1022, 798, 744,
697; dH (400 MHz, CDCl3): 7.58–7.54 (m,1H), 7.47–7.42 (m, 2H), 7.36–
7.21(m, 5H), 7.10–7.06 (m, 2H), 7.03(d, J¼0.8 Hz,1H), 4.62(t, J¼7.2 Hz,
2H), 3.22 (t, J¼7.2 Hz, 2H); dC (100.6 MHz, CDCl3) 154.9, 137.9, 136.5,
129.6, 128.9, 128.6, 127.4, 127.3, 126.9, 125.9, 123.4, 121.4, 112.6, 111.3,
84.3, 82.8, 51.9, 36.5;MS m/z313 (Mþ, 40), 284 (72), 257 (58),167(89),
166 (86), 139 (95), 138 (51), 126 (34), 105 (98), 103 (37), 91 (100), 79
(67), 77 (93), 65 (55), 63 (46), 51 (69%).
3.3. General procedure for the synthesis of compounds 3
To a solution (0.5–0.8 N) of aryl iodide (1 equiv) in DMF at room
temperature under nitrogen were successively added Pd(PPh3)4
(0.05 equiv), AgCl (0.2 equiv), and K2CO3 (8 equiv). The resulting
mixture was stirred for 5 min and then MeOH (8 equiv) was added
followed by a solution (0.2–0.3 N) of compound 2 (1 equiv) in DMF.
The mixture was stirred at room temperature (Table 2, entries 1 and
4–6) or at 40 ꢁC (Table 2, entries 2, 3, 7, and 8) and, after reaction
completion (2–18 h), was quenched with aqueous NH4Cl (20 mL)
and extracted with ethyl acetate (3ꢀ30 mL). The organic extracts
were washed with an aqueous solution of NaCl (3ꢀ20 mL), dried
over anhydrous Na2SO4, and concentrated under vacuum. The
3.3.4. 4-[(Thiophen-2-yl)ethynyl]-1-(2-phenylethyl)-1H-1,2,3-tri-
azole (3d). Compound 3d was prepared from 2d (0.200 g,
0.74 mmol) and 2-iodothiophene (0.155 g, 0.74 mmol) and the re-
action was performed at room temperature. Purification by column
chromatography (silica gel, 30% ethyl acetate/petroleum ether)
afforded 0.165 g of compound 3d (80% yield). After crystallization
from ethyl acetate/petroleum ether, compound 3d was obtained as
a yellow-orange solid, mp¼156–158 ꢁC. [Found: C, 68.85; H, 4.63; N,
15.08; S, 11.55. C16H13N3S requires C, 68.79; H, 4.69; N, 15.04; S,
11.48%.] nmax (KBr) 3131, 3099, 2953, 2928, 2863, 1456, 1436, 1329,

10578
V. Fiandanese et al. / Tetrahedron 65 (2009) 10573–10580
1230, 1217, 1184, 1108, 1052, 850, 830, 749, 717, 711, 701, 695; dH
(400 MHz, CDCl3) 7.38 (s, 1H), 7.32–7.20 (m, 5H), 7.12–7.05 (m, 2H),
6.98 (dd, J¼5.0, 3.8 Hz, 1H), 4.59 (t, J¼7.2 Hz, 2H), 3.20 (t, J¼7.2 Hz,
2H); dC (100.6 MHz, CDCl3) 136.5, 132.5, 130.3, 128.8, 128.5, 127.8,
127.1, 127.0, 126.1, 122.0, 85.6, 82.1, 51.7, 36.4; MS m/z 279 (Mþ, 24),
250 (72), 223 (53), 217 (25),191 (27),160 (26),133 (100),116 (25),105
(90), 91 (75), 89 (76), 79 (62), 77 (83), 65 (56), 51 (52), 45 (70%).
gel, 30% ethyl acetate/petroleum ether) afforded 0.144 g of com-
pound 3h (83% yield). After crystallization from ethyl acetate/pe-
troleum ether, compound 3h was obtained as a pale orange solid,
mp¼84–85 ꢁC. [Found: C, 67.80; H, 7.36; N, 15.79. C20H26N4O2 re-
quires C, 67.77; H, 7.39; N, 15.81%.] nmax (KBr) 3154, 2954, 2915,
2848, 2227, 1596,1511, 1467,1343,1049, 859, 811, 749; dH (400 MHz,
CDCl3) 8.17 (d, J¼7.9 Hz, 2H), 7.76 (s, 1H), 7.63 (d, J¼7.9 Hz, 2H), 4.36
(t, J¼7.2 Hz, 2H), 1.94–1.84 (m, 2H), 1.33–1.14 (m, 14H), 0.82 (t,
J¼6.8 Hz, 3H); dC (100.6 MHz, CDCl3) 147.1,132.2,129.9,129.2, 126.4,
123.6, 90.4, 83.8, 50.6, 31.7, 30.1, 29.3, 29.2, 29.1, 28.8, 26.3, 22.6,
14.0; MS m/z 214 (16), 201 (6), 186 (12), 173 (16), 167 (16), 155 (6),
154 (6), 153 (5), 143 (5), 141 (7), 127 (7), 126 (9), 113 (8), 83 (6), 70
(8), 69 (8), 67 (7), 63 (7), 57 (32), 55 (37), 43 (100), 41 (95%).
3.3.5. 4-(Phenylethynyl)-1-(2-phenylethyl)-1H-1,2,3-triazole
(3e). Compound 3e was prepared from 2d (0.200 g, 0.74 mmol) and
iodobenzene (0.151 g, 0.74 mmol) and the reaction was performed at
room temperature in accordance with general procedure. Purifica-
tion by column chromatography (silica gel, 30% ethyl acetate/pe-
troleum ether) afforded 0.174 g of compound 3e (86% yield). After
crystallization from ethyl acetate/petroleum ether, compound 3c
was obtained as a light brown solid, mp¼140–143 ꢁC. [Found: C,
79.13; H, 5.58; N, 15.42. C18H15N3 requires C, 79.10; H, 5.53; N,
15.37%.] nmax (KBr) 3125, 3070, 2953, 2929, 2864, 1484, 1457, 1437,
1348, 1229, 1210, 1053, 1026, 836, 757, 729, 697, 689; dH (400 MHz,
CDCl3) 7.53–7.47 (m, 2H), 7.40 (s, 1H), 7.36–7.20 (m, 6H), 7.09 (br d,
J¼7.2 Hz, 2H), 4.59 (t, J¼7.2 Hz, 2H), 3.21 (t, J¼7.2 Hz, 2H); dC
(100.6 MHz, CDCl3) 136.6,131.5,130.7,128.9,128.7,128.6,128.3,127.2,
126.1, 122.3, 92.3, 78.5, 51.8, 36.5; MS m/z 273 (Mþ, 3), 244 (16), 230
(2), 217 (10), 203 (7), 202 (8),168 (4),154 (6),141 (3),127 (37),113 (6),
105 (100), 91 (20), 79 (21), 77 (30), 65 (11), 63 (10), 51 (15%).
3.4. General procedure for the synthesis of compounds 4
A THF solution (0.2–0.3 M) of silylated derivative 3 (1 equiv) was
added at room temperature, under nitrogen, to a stirred suspension
(0.2–0.3 M) of azide (1.2 equiv) and CuI (1 equiv) in THF, then
1,1,4,7,7-pentamethyldiethylenetriamine (1.2 equiv) and soon af-
terward TBAF (1 M in THF, 1.2 equiv) were added. The mixture was
stirred at room temperature until reaction completion (2–4 h), then
was quenched with a saturated aqueous solution of NH4Cl (20 mL)
and extracted with ethyl acetate (3ꢀ50 mL). The organic extracts
were washed with H2O (3ꢀ30 mL), dried over Na2SO4, and con-
centrated under vacuum. The residue was purified by column
chromatography on silica gel and by crystallization.
3.3.6. 4-(Phenylethynyl)-1-(4-methoxyphenyl)-1H-1,2,3-triazole
(3f). Compound 3f was prepared from 2e (0.150 g, 0.55 mmol) and
iodobenzene (0.112 g, 0.55 mmol) and the reaction was performed
at room temperature. Purification by column chromatography
(silica gel, 40% ethyl acetate/petroleum ether) afforded 0.106 g of
compound 3f (70% yield). After crystallization from ethyl acetate/
petroleum ether, compound 3f was obtained as a bronze solid,
mp¼168–170 ꢁC. [Found: C, 74.20; H, 4.72; N, 15.20. C17H13N3O
requires C, 74.17; H, 4.76; N, 15.26%.] nmax (KBr) 3113, 3072, 1516,
1439, 1248, 1227, 1050, 1033, 1024, 832, 761, 692, 641; dH (400 MHz,
DMSO) 9.13 (s, 1H), 7.83 (d, J¼9.0 Hz, 2H), 7.65–7.55 (m, 2H), 7.50–
7.42 (m, 3H), 7.15 (d, J¼9.0 Hz, 2H), 3.83 (s, 3H); dC (100.6 MHz,
DMSO) 159.4, 131.2, 129.9, 129.4, 129.2, 128.8, 125.8, 121.8, 121.3,
114.8, 92.1, 79.0, 55.5; MS m/z 247 (100), 232 (31), 204 (48),176 (20),
152 (11), 151 (11), 124 (27), 116 (12), 102 (35), 88 (36), 75 (16), 63
(10), 51 (12%).
3.4.1. 1-Benzyl-10-(2-phenylethyl)-1H,10H-4,40-bi-1,2,3-triazole
(4a). Compound 4a was prepared from 2a (0.100 g, 0.39 mmol) and
2-phenylethylazide (0.069 g, 0.47 mmol) in accordance with gen-
eral procedure. Purification by column chromatography (silica gel,
from 60% to 80% ethyl acetate/petroleum ether) afforded 0.082 g of
compound 4a (64% yield). After washing with ethyl acetate, com-
pound 4a was obtained as a white solid, mp¼204–206 ꢁC. [Found:
C, 69.00; H, 5.43; N, 25.48. C19H18N6 requires C, 69.07; H, 5.49; N,
25.44%.] nmax (KBr) 3129, 3094, 3062, 3028, 2950, 2913, 2851, 1496,
1454, 1438, 1424, 1229, 1220, 1087, 1056, 958, 833, 709, 695; dH
(400 MHz, DMSO) 8.54 (s, 1H), 8.43 (s, 1H), 7.42–7.32 (m, 5H), 7.31–
7.24 (m, 2H), 7.23–7.17 (m, 3H), 5.64 (s, 2H), 4.67 (t, J¼7.2 Hz, 2H),
3.21 (t, J¼7.2 Hz, 2H); dC (100.6 MHz, DMSO) 139.3, 138.7, 137.5,
135.9, 128.7, 128.6, 128.3, 128.1, 127.9, 126.5, 121.6, 121.5, 52.8, 50.5,
35.4; MS m/z 273 (15),183 (18),156 (28), 154 (22), 129 (19), 128 (16),
105 (18), 91 (100), 77 (17), 65 (37), 51 (19), 44 (12%).
3.3.7. 4-[(4-Methylphenyl)ethynyl]-1-decyl-1H-1,2,3-triazole
(3g). Compound 3g was prepared from 2h (0.150 g, 0.49 mmol)
and 4-methyliodobenzene (0.107 g, 0.49 mmol) and the reaction
was performed at 40 ꢁC, in accordance with general procedure.
Purification by column chromatography (silica gel, 20% ethyl ace-
tate/petroleum ether) afforded 0.106 g of compound 3g (67% yield).
After crystallization from ethyl acetate/petroleum ether, compound
3g was obtained as a light brown solid, mp¼95–96 ꢁC. [Found: C,
77.93; H, 9.00; N, 13.02. C21H29N3 requires C, 77.97; H, 9.04; N,
12.99%.] nmax (KBr) 3123, 2954, 2914, 2847, 1503, 1465, 1458, 1234,
1050, 812; dH (400 MHz, CDCl3) 7.65 (s, 1H), 7.40 (d, J¼8.2 Hz, 2H),
7.12 (d, J¼8.2 Hz, 2H), 4.33 (t, J¼7.2 Hz, 2H), 2.33 (s, 3H), 1.93–1.82
(m, 2H), 1.33–1.15 (m, 14H), 0.84 (t, J¼6.8 Hz, 3H); dC (100.6 MHz,
CDCl3) 138.9, 131.4, 131.0, 129.1, 125.5, 119.2, 92.5, 77.9, 50.5, 31.8,
30.1, 29.4, 29.3, 29.2, 28.9, 26.3, 22.6, 21.5, 14.1; MS m/z 323 (Mþ, 4),
295 (4), 294 (3), 266 (3), 252 (3), 238 (4), 224 (5), 210 (6), 196 (9),
183 (23), 182 (29), 168 (26), 155 (38), 142 (25), 139 (19), 128 (23), 115
(16), 105 (10), 70 (8), 69 (7), 57 (20), 55 (35), 43 (86), 41 (100%).
3.4.2. 1-Benzyl-10-(3-phenylpropyl)-1H,10H-4,40-bi-1,2,3-triazole
(4b). Compound 4b was prepared from 2a (0.092 g, 0.36 mmol)
and 3-phenylpropylazide (0.069 g, 0.43 mmol) in accordance with
general procedure. Purification by column chromatography (silica
gel, from 60% to 80% ethyl acetate/petroleum ether) afforded
0.081 g of compound 4b (65% yield). After washing with ethyl ac-
etate, compound 4b was obtained as a white solid, mp¼188–190 ꢁC.
[Found: C, 69.80; H, 5.88; N, 24.50. C20H20N6 requires C, 69.75; H,
5.85; N, 24.40%.] nmax (KBr) 3136, 3091, 3031, 2940, 2863, 1496,
1456, 1430, 1305, 1223, 1087, 1057, 964, 847, 749, 722, 693; dH
(400 MHz, DMSO) 8.57 (s, 1H), 8.56 (s, 1H), 7.45–7.13 (m, 10H), 5.67
(s, 2H), 4.42 (t, J¼6.8 Hz, 2H), 2.57 (t, J¼7.6 Hz, 2H), 2.24–2.12 (m,
2H); dC (100.6 MHz, DMSO) 140.6, 139.4, 139.0, 135.9, 128.7, 128.3,
128.2, 128.1, 127.9, 125.9, 121.7, 121.5, 52.9, 49.0, 31.8, 31.2; MS m/z
344 (Mþ, 6), 287 (10), 259 (3), 258 (4), 197 (5), 183 (9), 170 (6), 156
(11), 154 (11), 143 (6), 128 (9), 117 (6), 115 (6), 91 (100), 77 (8), 65
(31), 52 (9), 51 (11), 41 (16%).
3.3.8. 4-[(4-Nitrophenyl)ethynyl]-1-decyl-1H-1,2,3-triazole
(3h). Compound 3h was prepared from 2h (0.150 g, 0.49 mmol)
and 4-nitroiodobenzene (0.122 g, 0.49 mmol) and the reaction was
performed at 40 ꢁC. Purification by column chromatography (silica
3.4.3. 1-Benzyl-10-decyl-1H,10H-4,40-bi-1,2,3-triazole (4c). Compound
4c was prepared from 2a (0.100 g, 0.39 mmol) and n-decylazide
(0.086 g, 0.47 mmol) in accordance with general procedure.

V. Fiandanese et al. / Tetrahedron 65 (2009) 10573–10580
10579
Purification by column chromatography (silica gel, from 60% to 80%
ethyl acetate/petroleum ether) afforded 0.107 g of compound 4c
(75% yield). After washing with ethyl acetate, compound 4c was
obtained as a white solid, mp¼175–176 ꢁC. [Found: C, 68.80; H,
8.28; N, 22.88. C21H30N6 requires C, 68.82; H, 8.25; N, 22.93%.] nmax
(KBr) 3136, 3075, 2954, 2918, 2846, 1457, 1438, 1220, 1085, 1055,
719, 695; dH (400 MHz, CDCl3) 8.02 (s, 1H), 7.95 (s, 1H), 7.39–7.24
(m, 5H), 5.54 (s, 2H), 4.36 (t, J¼7.0 Hz, 2H), 1.95–1.82 (m, 2H), 1.35–
1.10 (m, 14H), 0.83 (t, J¼6.6 Hz, 3H); dC (100.6 MHz, CDCl3) 140.5,
140.0, 134.2, 129.1, 128.8, 128.2, 120.5, 120.4, 54.3, 50.4, 31.8, 30.2,
29.4, 29.3, 29.2, 28.9, 26.3, 22.6, 14.0; MS m/z 219 (12), 197 (8), 183
(8), 169 (9), 156 (15), 154 (12), 144 (9), 128 (10), 91 (100), 80 (10), 70
(14), 65 (21), 55 (25), 43 (43), 41 (59%).
2.27 (quintet, J¼7.2 Hz, 2H), 1.97–1.87 (m, 2H), 1.36–1.16 (m, 10H),
0.84 (t, J¼6.8 Hz, 3H); dC (100.6 MHz, CDCl3) 140.2, 140.0, 140.0,
128.6, 128.4, 126.3, 120.5, 120.4, 50.5, 49.6, 32.4, 31.6, 31.6, 30.2,
29.0, 28.9, 26.4, 22.5, 14.0; MS m/z 211 (19), 182 (20), 170 (19), 121
(20), 107 (16), 94 (25), 93 (23), 91 (66), 80 (34), 67 (18), 65 (24), 55
(24), 53 (22), 43 (51), 41 (100%).
3.4.7. 1-Octyl-10-(4-methoxyphenyl)-1H,10H-4,40-bi-1,2,3-triazole
(4g). Compound 4g was prepared from 2g (0.150 g, 0.54 mmol) and
4-methoxyphenylazide (0.097 g, 0.65 mmol) in accordance with
general procedure. Purification by column chromatography (silica
gel, from 60% to 80% ethyl acetate/petroleum ether) afforded
0.126 g of compound 4g (66% yield). After crystallization from ethyl
acetate/petroleum ether, compound 4g was obtained as a light
brown solid, mp¼166–168 ꢁC. [Found: C, 64.41; H, 7.33; N, 23.78.
C19H26N6O requires C, 64.38; H, 7.39; N, 23.71%.] nmax (KBr) 3114,
2954, 2919, 2850, 1522, 1464, 1438, 1306, 1254, 1237, 1111, 1087,
1044, 1028, 835, 819; dH (400 MHz, CDCl3) 8.40 (s, 1H), 8.08 (s, 1H),
7.66 (d, J¼8.8 Hz, 2H), 7.02 (d, J¼8.8 Hz, 2H), 4.41 (t, J¼7.2 Hz, 2H),
3.85 (s, 3H), 1.99–1.87 (m, 2H), 1.40–1.15 (m, 10H), 0.84 (t, J¼6.8 Hz,
3H); dC (100.6 MHz, CDCl3) 159.9, 140.7, 139.8, 130.3, 122.1, 120.6,
118.7, 114.8, 55.6, 50.6, 31.7, 30.2, 29.0, 28.9, 26.4, 22.6, 14.0; MS m/z
298 (23), 199 (22), 171 (17), 156 (24), 134 (26), 107 (14), 92 (19), 80
(20), 77 (23), 66 (17), 64 (17), 55 (28), 43 (50), 41 (100%).
3.4.4. 1-Benzyl-10-octyl-1H,10H-4,40-bi-1,2,3-triazole (4d). Compound
4d was prepared from 2a (0.200 g, 0.78 mmol) and n-octylazide
(0.146 g, 0.94 mmol) in accordance with general procedure. Puri-
fication by column chromatography (silica gel, from 60% to 80%
ethyl acetate/petroleum ether) afforded 0.164 g of compound 4d
(62% yield). After crystallization from ethyl acetate/petroleum
ether, compound 4d was obtained as a white solid, mp¼177–
178 ꢁC. [Found: C, 67.40; H, 7.80; N, 24.88. C19H26N6 requires C,
67.43; H, 7.74; N, 24.83%.] nmax (KBr) 3136, 3096, 3076, 2954, 2916,
2870, 2847, 1494, 1455, 1441, 1429, 1300, 1224, 1084, 1055, 960, 842,
833, 719, 709, 695; dH (400 MHz, CDCl3) 8.01 (s, 1H), 7.95 (s, 1H),
7.38–7.26 (m, 5H), 5.54 (s, 2H), 4.36 (t, J¼7.0 Hz, 2H), 1.94–1.83 (m,
2H),1.35–1.14 (m,10H), 0.83 (t, J¼6.8 Hz, 3H); dC (100.6 MHz, CDCl3)
140.5, 139.9, 134.2, 129.1, 128.8, 128.2, 120.5, 120.3, 54.3, 50.4, 31.6,
30.2, 29.0, 28.9, 26.4, 22.5, 14.0; MS m/z 338 (Mþ, 6), 281 (5), 225
(5), 197 (7), 191 (14), 183 (7), 169 (8), 156 (13), 154 (11), 144 (8), 128
(11), 91 (100), 80 (10), 70 (14), 65 (27), 55 (17), 43 (37), 41 (68%).
Compound 4d was prepared from 2g (0.400 g, 1.44 mmol) and
benzyl azide (0.230 g, 1.73 mmol) in accordance with general pro-
cedure. Purification by column chromatography (silica gel, from
60% to 80% ethyl acetate/petroleum ether) afforded 0.419 g of
compound 4d (86% yield).
Acknowledgements
This work was financially supported by the University of Bari.
We thank Mrs. Marianna Fittipaldi for preliminary experiments.
References and notes
1. (a) Morales-Sanfrutos, J.; Ortega-Munoz, M.; Lopez-Jaramillo, J.; Hernandez-
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3.4.5. 1-Octyl-10-decyl-1H,10H-4,40-bi-1,2,3-triazole (4e). Compound
4e was prepared from 2g (0.199 g, 0.72 mmol) and n-decylazide
(0.157 g, 0.86 mmol) in accordance with general procedure. Purifi-
cation by column chromatography (silica gel, from 60% to 80% ethyl
acetate/petroleum ether) afforded 0.145 g of compound 4e (52%
yield). After crystallization from ethyl acetate/petroleum ether,
compound 4e was obtained as a white solid, mp¼165–166 ꢁC.
[Found: C, 68.05; H, 10.32; N, 21.68. C22H40N6 requires C, 68.00; H,
10.38; N, 21.63%.] nmax (KBr) 3141, 3106, 2957, 2929, 2847, 1465,
1261, 1222, 1103, 1084, 1057, 1022, 801; dH (400 MHz, CDCl3) 8.03 (s,
2H), 4.37 (t, J¼7.2 Hz, 4H), 1.96–1.84 (m, 4H), 1.36–1.13 (m, 24H),
0.83 (t, J¼6.8 Hz, 6H); dC (100.6 MHz, CDCl3) 140.2, 120.4, 50.5, 31.8,
31.6, 30.2, 29.4, 29.3, 29.2, 29.0, 28.9, 28.9, 26.4, 22.6, 22.5, 14.0,
14.0; MS m/z 275 (7), 247 (9), 166 (6), 162 (5), 148 (7), 135 (8), 121
(11), 120 (12), 108 (14), 94 (15), 93 (16), 80 (23), 70 (15), 68 (13), 67
(13), 57 (21), 55 (38), 43 (87), 41 (100%).
3.4.6. 1-Octyl-10-(3-phenylpropyl)-1H,10H-4,40-bi-1,2,3-triazole
(4f). Compound 4f was prepared from 2g (0.379 g, 1.37 mmol) and
3-phenylpropylazide (0.264 g, 1.64 mmol) in accordance with
general procedure. Purification by column chromatography (silica
gel, from 60% to 80% ethyl acetate/petroleum ether) afforded
0.391 g of compound 4f (78% yield). After crystallization from ethyl
acetate/petroleum ether, compound 4f was obtained as a white
solid, mp¼152–153 ꢁC. [Found: C, 68.80; H, 8.28; N, 22.88. C21H30N6
requires C, 68.82; H, 8.25; N, 22.93%.] nmax (KBr) 3136, 3102, 2953,
2916, 2849, 1458, 1438, 1425, 1304, 1234, 1221, 1086, 1055, 959, 952,
839, 744, 697; dH (400 MHz, CDCl3) 8.03 (s, 2H), 7.30–7.13 (m, 5H),
4.39 (t, J¼7.2 Hz, 2H), 4.38 (t, J¼7.2 Hz, 2H), 2.65 (t, J¼7.2 Hz, 2H),
9. Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A. Tetrahedron Lett. 2003, 44,
9087–9090.
10. (a) Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A. Tetrahedron 2004, 60,
11421–11425; (b) Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A. J. Orga-
nomet. Chem. 2005, 690, 3004–3008; (c) Fiandanese, V.; Bottalico, D.;
Cardellicchio, C.; Marchese, G.; Punzi, A. Tetrahedron 2005, 61, 4551–4556; (d)
Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A. Tetrahedron 2006, 62,
5126–5132.
11. For a comprehensive review, see: Fiandanese, V.; Bottalico, D. Curr. Org. Chem.
2009, 13, 554–572.

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12. Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A. Tetrahedron 2008, 64,
53–60.
15. West, K.; Hayward, L. N.; Batsanov, A. S.; Bryce, M. R. Eur. J. Org. Chem. 2008,
5093–5098.
13. Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A. Tetrahedron 2008, 64,
7301–7306.
16. Fletcher, J. T.; Bumgarner, B. J.; Engels, N. D.; Skoglund, D. A. Organometallics
2008, 27, 5430–5433.
14. Reck, F.; Zhou, F.; Girardot, M.; Kern, G.; Eyermann, C. J.; Hales, N. J.; Ramsay, R. R.;
Gravestock, M. B. J. Med. Chem. 2005, 48, 499–506.
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