One-pot click synthesis of 1N-alkyl-4-aryl-1,2,3-triazoles from protected arylalkynes and alkyl bromides

Article abstract of DOI:10.1055/s-0030-1260256

1N-Alkyl-4-aryl-1,2,3-triazoles have been prepared through a multicomponent one-pot protocol from the corresponding (arylethynyl)trimethylsilanes and alkyl bromides. In situ alkyl azide formation and alkyne deprotection followed by copper(I)-catalyzed click cycloaddition afforded the desired 1,4-disubstituted 1,2,3-triazoles in generally good to excellent yield, with only minor observation of the undesired 1,5-regioisomeric cycloadduct. The protocol eliminates the need to use reactive organic azides and terminal alkynes. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0030-1260256

3604
PRACTICAL SYNTHETIC PROCEDURES
One-Pot Click Synthesis of 1N-Alkyl-4-aryl-1,2,3-triazoles from Protected
Arylalkynes and Alkyl Bromides
Sébastien Ladouceur, Ahmed M. Soliman, Eli Zysman-Colman*
Département de chimie, Université de Sherbrooke, 2500 Boul. Université, Sherbrooke, Québec, J1K 2R1, Canada
Fax +1(819)8218017; E-mail: Eli.Zysman-Colman@usherbrooke.ca
PSP
Received 11 August 2011; revised 7 September 2011
No209
Abstract: 1N-Alkyl-4-aryl-1,2,3-triazoles have been prepared through a multicomponent one-pot protocol from the corresponding (aryl-
ethynyl)trimethylsilanes and alkyl bromides. In situ alkyl azide formation and alkyne deprotection followed by copper(I)-catalyzed click
cycloaddition afforded the desired 1,4-disubstituted 1,2,3-triazoles in generally good to excellent yield, with only minor observation of the
undesired 1,5-regioisomeric cycloadduct. The protocol eliminates the need to use reactive organic azides and terminal alkynes.
Key words: click chemistry, Huisgen cycloaddition, triazoles, alkynes, azides
one-pot protocol
R
N
N
N
TMS
+
deprotection
azide formation
N
N
R
N
+
RBr
Ar
Ar
Ar
2
click cycloaddition
3
1,4-isomer
1
+
NaN3
1,5-isomer
+
RN3
Ar
Scheme 1 Practical, one-pot three-step synthesis of triazoles through in situ deprotection of a trimethylsilylated alkyne and formation of an
alkyl azide from the corresponding alkyl halide, followed by cycloaddition
Since the discovery1 almost 10 years ago of the copper(I)- fort toward the development of multicomponent or one-
catalyzed [3+2] Huisgen2 1,3-dipolar cycloaddition be- pot variations that would avoid the isolation of small mo-
tween an azide and an alkyne, commonly classified as a lecular weight organic azides and organic terminal
‘click’ reaction,3 1,4-disubstituted 1,2,3-triazoles can now alkynes. Several groups have demonstrated that in situ
be efficiently and regioselectively formed (e.g., 2; azide preparation from the corresponding aromatic or ali-
CuAAC reaction).4 This heterocyclic motif has been ex- phatic halide is compatible with the CuAAC reaction.12
tensively exploited in myriad applications from catalysis,5 Recently, Fletcher and co-workers10d amongst others
to materials,6 to bioimaging,7 to pharmaceuticals.8 Less showed that click triazole formation can proceed with in
explored is the use of the triazole motif as a chelating situ deprotection of the trimethylsilyl group attached to
ligand.9 For instance, the incorporation of pyridyl-substi- the alkyne.10g,13 Novák and co-workers demonstrated that
tuted 1,2,3-triazoles (pytl) has only recently been exploit- aryl halides could be transformed into their corresponding
ed as bipyridine or terpyridine surrogates used in triazoles in good yield in a one-pot, sequential Sonogash-
organometallic complexes, especially those of rutheni- ira reaction with ethynyltrimethylsilane [(trimethylsi-
um.10 To our knowledge, the corresponding 4-aryl-substi- lyl)acetylene, TMSA], alkyne deprotection and click
tuted 1,2,3-triazoles (atl) have to date been investigated reaction sequence.14 Finally, Crowley and Bandeen
only cursorily as cyclometalating ligand analogues to demonstrated in a single example the in situ deprotection
arylpyridines (apy).11 Our interest lays in the investigation of a diyne using a silver(I) salt with concomitant form-
of the photophysical properties of iridium-based hetero- ation of the azide prior to click cycloaddition.15
leptic compounds incorporating atl ligands and their facile
access was required for efficient materials development.
action with respect to starting material formation, we re-
Taking advantage of the orthogonality of the CuAAC re-
In order to render the triazole-forming reaction that much port herein an efficient and safe one-pot protocol
more user-friendly and safe, there has been increasing ef- involving at once the trimethylsilyl deprotection of the
alkyne and azide formation/click reaction (Scheme 1). In
addition to (1) improving the synthetic efficiency, (2)
demonstrating that our one-pot protocol is scalable and (3)
showing that multiple click reactions can be performed on
SYNTHESIS 2011, No. 22, pp 3604–3611
Advanced online publication: 06.10.2011
DOI: 10.1055/s-0030-1260256; Art ID: M79111SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
1

PRACTICAL SYNTHETIC PROCEDURES
One-Pot Click Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
3605
the same substrate in good yield, the inherent advantage of bromide was used as the bromoalkane. With smaller mo-
this procedure is that sensitive terminal alkynes and azides lecular weight haloalkanes, frequently no precipitation
are formed in situ and immediately reacted to afford the was observed but the pure product could be readily ex-
desired 1,2,3-triazole.
tracted with dichloromethane. Yields reported in this
work represent the average of at least two runs. Pyridine
was found to be an important additive for the acceleration
of the deprotection of the alkyne under the reaction condi-
tions;16 pyridine was not required for substrates already
containing a pyridine motif, such as 1n.10d Generally and
not unexpectedly for a CuAAC reaction, the reaction was
regioselective for the 1,4-isomer, 2.
Aromatic and heteroaromatic substrates 1a–s were readily
obtained from the haloarenes via Sonogashira coupling
with TMSA. These substrates were stirred at room tem-
perature in methanol–water (1:1, v/v) at 0.15–0.30 M con-
centration in the presence of the alkyl bromide, sodium
azide, copper(II) sulfate, ascorbic acid, pyridine and po-
tassium carbonate. The scale of the reactions in Table 1
was on the order of 0.7 to 1.0 mmol based on starting The reaction proceeded readily in the presence of simple
alkyne 1 but experiments of up to 10 mmol were also con- electron-donating groups (Table 1, entries 2–5) or elec-
ducted without a noticeable decrease in isolated yield. In tron-withdrawing groups (entries 6–11). Yields were gen-
several cases (see Tables 1 and 2, and Scheme 2), the ad- erally higher for electron-poor arenes, ostensibly due to
dition of tetrahydrofuran as a cosolvent (MeOH–H2O– weaker h2-complexation of the copper with the alkyne.
THF, 1:1:1) resulted in increased solubility of the starting Chemoselectivity was reduced in the presence of phenolic
alkyne and/or intermediates and a corresponding increase oxygens (1b, entry 2) and anilinic nitrogens (entry not
in overall isolated yield. For example, yields in the ab- shown) as these heteroatoms were susceptible to alkyla-
sence of tetrahydrofuran for 2q, 2s and 2y dropped to tion under the reaction conditions. The triazole 2b, which
58%, 50% and 45%, respectively. For the purposes of was readily soluble in the reaction solvent system, could
evaluation of the synthetic protocol, the reaction progres- be isolated in 61% yield by first precipitation of its O-ben-
sion was followed by TLC and conversion was deter- zylated side product, 1-benzyl-4-[4-(benzyloxy)phenyl]-
mined by GC-MS. After the reaction was quenched with 1H-1,2,3-triazole (11% yield), followed by dichlo-
aqueous ammonium hydroxide, in most cases, the pure romethane extraction. Unsubstituted anilines were incom-
aryltriazoles could be isolated by filtration when benzyl patible substrates within our protocol; these substrates
Table 1 One-Pot Synthesis of Triazoles 2a–s
BnBr, NaN3
K2CO3, CuSO4
Bn
N
N
N
TMS
N
+
N
N
Bn
pyridine
ascorbic acid
MeOH–H2O (1:1)
18–24 h
Ar
Ar
Ar
1
2
3
Entry Ar
Product ratioa 2/3 Yieldb (%) Entry Ar
Product ratioa 2/3 Yieldb (%)
1
2
3
4
5
Ph
1a
1b
1c
1d
1e
6:1
1:0
1:0
1:0
1:0
2a/3a
2b/3b
2c/3c
2d/3d
2e/3e
80
61c
61
74
72
11
12
13
14
15
2-O2NC6H4
2-Tol
1k
1l
1:0
1:0
1:0
1:0
4:1
2k/3k
2l/3l
75
86
4-HOC6H4
4-MeOC6H4
3-MeOC6H4
4-Me2NC6H4
1-naphthyl
2-pyridyl
2-thienyl
1m
1n
1o
2m/3m 76
2n/3n
2o/3o
57
65
6
7
8
4-BrC6H4
1f
1:0
1:0
1:0
2f/3f
88
84
76
16
1p
1q
1r
1s
1:0
1:0
1:0
1:0
2p/3p
2q/3q
2r/3r
2s/3s
91
96
70
80
Br
N
2,4-F2C6H3
4-MeO2CC6H4
1g
1h
2g/3g
2h/3h
17d
18
N
N
N
9
4-O2NC6H4
3-O2NC6H4
1i
1j
1:0
1:0
2i/3i
2j/3j
77
62
19d
N
N
10
a Ratio determined by comparison of the alkenyl proton integrations in the 1H NMR spectrum of the crude reaction mixture.
b Average isolated yield over two runs.
c 11% of O-benzylated product was also isolated, see text.
d The solvent system MeOH–H2O–THF (1:1:1) was used, see text.
Synthesis 2011, No. 22, 3604–3611 © Thieme Stuttgart · New York

3606
S. Ladouceur et al.
PRACTICAL SYNTHETIC PROCEDURES
yielded a series of inseparable benzylated products with
only slight formation of the desired aryltriazole, as detect-
ed by 1H NMR spectroscopy. Substitution at the ortho po-
sition seems not to impede reaction yields (Table 1,
entries 11–13); however, the presence of an ortho-vinyl
substituent resulted in a complicated mixture of unidenti-
fied products (entry not shown), which suggests that the
alkene is not a passive substituent under the reaction con-
ditions.
Br
+
1g
Br
Br
4
1 equiv
3.1 equiv
NaN3, K2CO3, CuSO4
pyridine
ascorbic acid
MeOH–THF–H2O (1:1:1)
22 h
Alkynylheteroarenes also are compatible substrates under
the reaction conditions (Table 1, entries 14–19). Entries
17 and 19 demonstrate the effectiveness of the protocol,
signifying that multiple triazoles can be installed on mul-
tiple alkynyl sites. This strategy was carried further with
the formation of a tris(triazole) structure 2y from the cor-
responding tris(azide) in good yield (Scheme 2).
N
N
N
F
F
N
N
N
F
N
N
F
Alkyl, benzyl and allyl halides were readily converted
into the corresponding azides prior to cycloaddition and
yields of the corresponding aryltriazoles remained good
(Table 2). The use of iodomethane resulted in decreased
yield, perhaps due to the instability of the corresponding
methyl azide under the reaction conditions (entry 2); the
inclusion of tetrahydrofuran in the solvent mixture did not
result in an elevated yield in this case. In contrast, the ad-
dition of tetrahydrofuran proved beneficial when lipo-
philic alkyl halides were used as substrates (entries 4 and
5), with isolated yields increasing by ca. 40%. The trans-
formation of tert-butyl bromide into the corresponding
azide proved sluggish and resulted in poor conversions
into the corresponding triazole (entry 3).
F
N
2y 82%
F
Scheme 2 Formation of a tris(aryltriazole) derivative
lation. This improvement to the classic click reaction,
which precludes the necessity for isolation of potentially
explosive and toxic terminal alkynes and organic azides,17
will facilitate the preparation of libraries of 1,2,3-triazoles
for myriad applications.
In conclusion, a broad series of 1N-alkyl-4-aryl-1,2,3-tri-
azoles was prepared via an expedient, safe and efficient
multicomponent one-pot protocol. Alkyne deprotection
and azide formation proceeded in tandem with the click
Commercial reagents were used as supplied. All reactions were per-
formed using standard Schlenk techniques under an inert (N2) atmo-
sphere, save for the click reactions which were carried out in air.
Solvents were purified either by distillation or via a solvent purifi-
reaction, without the need for azide or terminal alkyne iso- cation system. Flash column chromatography was performed using
silica gel. Analytical thin-layer chromatography (TLC) was per-
Table 2 One-Pot Synthesis of Triazoles Bearing Various Alkyl Groups Appended to the Triazolyl Nitrogen
RX, NaN3
K2CO3, CuSO4
R
N
N
N
TMS
N
+
N
N
R
pyridine
ascorbic acid
MeOH–H2O (1:1)
19–24 h
Ar
Ar
Ar
1
2
3
Entry
Ar
RX
Product ratioa 2/3
Yieldb (%)
1
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
1c
BnBr
1:0
1:0
1:0
1:0
1:0
1:0
2c/3c
2t/3t
61
2
1c
1c
1c
1c
1c
MeI
41
3
t-BuBr
2u/3u
2v/3v
2w/3w
2x/3x
(38)c
68
4d
5d
6
Me(CH2)5Br
HO(CH2)6I
H2C=CHCH2Br
62
66
a Ratio determined by comparison of the alkenyl proton integrations in the 1H NMR spectrum of the crude reaction mixture.
b Average isolated yield over two runs.
c 2u/1c (1:5) by 1H NMR spectroscopy.
d The solvent system MeOH–H2O–THF (1:1:1) was used, see text.
Synthesis 2011, No. 22, 3604–3611 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
One-Pot Click Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
3607
formed with silica gel plates with aluminum backing. Compounds
were visualized under UV light. 1H and 13C NMR spectra were re-
corded on a Bruker Avance 400 spectrometer operating at 400 MHz
and 100 MHz, respectively, or on a Bruker Avance 300 spectrome-
ter operating at 300 MHz and 75 MHz, respectively. Deuterated
chloroform (CDCl3) was used as the solvent of record, except where
noted. Spectra were referenced to the solvent peak. Melting points
were recorded using open-end capillaries and are uncorrected. Mass
spectra (MS) were recorded on a VG Micromass ZAB-2F spectrom-
eter at the Université de Sherbrooke. All reported yields are isolated
yields. Yields for the click reactions are the average of at least two
runs. 1-Bromo-4-methoxybenzene,18 4-bromo-N,N-dimethyl-
aniline,18 2-bromo-5-iodopyridine,18 5-bromo-2-iodopyridine19 and
6-iodohexanol20 were prepared following literature procedures and
their characterization corresponds to that given in the literature. Bi-
pyridine 1s21 and 5-bromo-2,2¢-bipyridine22 were each prepared us-
ing a Negishi coupling protocol and their characterization
corresponds to that given in the literature. 1,3,5-Tris(bromometh-
yl)benzene (4) was prepared using a two-step one-pot protocol;23
the characterization for 4 is in agreement with that previously re-
ported.24 All electron-deficient and electron-rich (arylethynyl)tri-
methylsilanes 1 were prepared according to the following protocols.
GC-MS: m/z (%) = 210 (100) (tR = 7.49 min).
LRMS (EI, 70 eV): m/z = 210 [M+], 195, 133, 77.
HRMS (EI, 70 eV): m/z calcd for C11H12F2Si: 210.0676; found:
210.0679.
5-[(Trimethylsilyl)ethynyl]-2,2¢-bipyridine (1r)
Yield: 94%; brown solid; mp 53–55 °C (Lit.25 45–46 °C); Rf = 0.38
(EtOAc–hexanes, 1:9).
1H NMR (300 MHz, CDCl3): d = 8.73 (d, J = 1.8 Hz, 1 H), 8.68 (d,
J = 4.3 Hz, 1 H), 8.38 (dd, J = 11.7, 8.1 Hz, 2 H), 7.87 (dd, J = 8.3,
2.2 Hz, 1 H), 7.85–7.77 (m, 1 H), 7.32 (ddd, J = 7.3, 4.7, 0.9 Hz, 1
H), 0.28 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 155.6, 155.1, 152.2, 149.4, 139.9,
137.1, 124.1, 121.5, 120.3, 101.9, 99.3, –0.02.
LRMS (EI, 70 eV): m/z = 252 [M+], 237, 221.
HRMS (EI, 70 eV): m/z calcd for C15H16N2Si: 252.1083; found:
252.1088.
The 1H NMR spectrum is in agreement with that previously
reported25 but the 13C NMR spectrum was found to be different.
4-[(Trimethylsilyl)ethynyl]phenyl Acetate (Acetate Derivative
of 1b)
Yield: 86%; beige solid; mp 73 °C; Rf = 0.52 (EtOAc–hexanes,
2:8).
1H NMR (400 MHz, CDCl3): d = 7.47 (d, J = 8.8 Hz, 2 H), 7.03 (d,
J = 8.8 Hz, 2 H), 2.29 (s, 3 H), 0.24 (s, 9 H).
13C NMR (101 MHz, CDCl3): d = 169.1, 150.6, 133.2, 121.6, 120.9,
104.2, 94.4, 21.2, 0.0.
(Arylethynyl)trimethylsilanes 1; General Procedure for Elec-
tron-Deficient Arenes
Pd(PPh3)4 (0.5 mol%) and CuI (1.0 mol%) were degassed in a
flame-dried round-bottom flask. Et3N (0.3 to 0.4 M) was added with
the desired bromoarene (1.00 equiv). The solution was degassed
again and then (trimethylsilyl)acetylene (TMSA, 1.50 equiv) was
added. The reaction mixture was heated to reflux for a 24-h period
and then allowed to cool to r.t. The black solution was diluted with
CH2Cl2 and then treated with 0.1 N aq HCl until the aqueous layer
was at pH 1. The aqueous solutions were extracted multiple times
with CH2Cl2. All organic phases were combined, dried (anhyd
MgSO4), filtered through a Celite® plug and concentrated under re-
duced pressure to obtain the crude product. The product was puri-
fied via flash column chromatography using silica gel as the
stationary phase and hexanes or a mixture of hexanes and EtOAc to
obtain the final product.
LRMS (EI, 70 eV): m/z = 232 [M+], 217, 190, 175, 146, 115, 105.
HRMS (EI, 70 eV): m/z calcd for C13H16O2Si: 232.0920; found:
232.0925.
4-[(Trimethylsilyl)ethynyl]phenol (1b)
4-[(Trimethylsilyl)ethynyl]phenyl acetate (498.4 mg, 2.14 mmol,
1.00 equiv) was dissolved in a mixture of THF, MeOH and H2O
(1:1:1, 15 mL) to obtain a concentration of ca. 0.15 M. The solution
was cooled to 0 °C and LiOH·H2O (185.4 mg, 4.42 mmol, 2.05
equiv) was added. The solution was stirred for 30 min. The reaction
mixture was diluted with 1 N aq HCl (50 mL), and was extracted
with Et2O. All organic layers were combined, dried (anhyd
MgSO4), filtered and concentrated under reduced pressure to obtain
a brown oil. The crude product was purified by flash column chro-
matography using a gradient of 10% to 15% EtOAc in hexanes to
give a white solid; yield: 347.0 mg (85%). The characterization was
found to be different to that given in the literature.26
(Arylethynyl)trimethylsilanes 1; General Procedure for Elec-
tron-Rich Arenes
Pd(OAc)2 trimer (3.0 mol%), [t-Bu3PH]+BF4– (6.0 mol%) and CuI
(0.60 mol%) were degassed in a flame-dried round-bottom flask.
Et3N–i-Pr2NH (1:1) (0.3 to 0.4 M in total) was added with the de-
sired bromoarene (1.00 equiv). The solution was degassed again
and then TMSA (1.50 equiv) was added. The reaction mixture was
heated to reflux for a 24-h period; progression of the reaction was
followed by GC-MS. The reaction mixture was cooled to r.t. The
black solution was diluted with CH2Cl2 and then treated with 0.1 N
aq HCl until the aqueous layer was at pH 1. The aqueous solutions
were extracted multiple times with CH2Cl2. All organic phases were
combined, dried (anhyd MgSO4), filtered through a Celite® plug
and concentrated under reduced pressure to obtain the crude prod-
uct. The product was purified via flash column chromatography us-
ing silica gel as the stationary phase and hexanes or a mixture of
hexanes and EtOAc to obtain the final product.
Mp 63–64 °C; Rf = 0.25 (Et2O–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 7.36 (d, J = 8.8 Hz, 2 H), 6.75 (d,
J = 8.8 Hz, 2 H), 5.24 (s, 1 H), 0.24 (s, 9 H).
13C NMR (101 MHz, CDCl3): d = 155.8, 133.8, 115.6, 115.5, 105.3,
92.8, 0.2.
LRMS (EI, 70 eV): m/z = 190 [M+], 175, 115, 87.
HRMS (EI, 70 eV): m/z calcd for C11H14OSi: 190.0814; found:
190.0817.
New Spectroscopic Data for the (Arylethynyl)trimethylsilanes 1
[(2,4-Difluorophenyl)ethynyl]trimethylsilane (1g)
Yield: 95%; clear oil; Rf = 0.38 (hexanes).
1H NMR (400 MHz, CDCl3): d = 7.17 (dd, J = 8.1, 15.2 Hz, 1 H),
6.55 (dd, J = 5.1, 12.8 Hz, 2 H), 0.00 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 164.5 (dd, J = 11.8, 66.0 Hz),
162.0 (dd, J = 11.8, 63.7 Hz), 135.0 (dd, J = 2.6, 9.8 Hz), 111.6 (dd,
J = 3.8, 21.4 Hz), 108.3 (dd, J = 4.0, 16.0 Hz), 104.4 (t, J = 25.4
Hz), 100.0 (s), 97.0 (s), 0.01 (s).
1,4-Disubstituted 1,2,3-Triazoles 2; General Procedure for the
Click Reactions
K2CO3 (1.80 equiv), CuSO4 (0.20 equiv), NaN3 (1.10 equiv) and L-
ascorbic acid (0.40 equiv) were added to a scintillation vial contain-
ing a magnetic stirrer bar. A mixture of H2O and MeOH (1:1) was
added to obtain a concentration of 0.15 to 0.20 M. The desired (aryl-
ethynyl)trimethylsilane 1 (1.00 equiv) was added and the solution
Synthesis 2011, No. 22, 3604–3611 © Thieme Stuttgart · New York

3608
S. Ladouceur et al.
PRACTICAL SYNTHETIC PROCEDURES
was vigorously stirred. The desired alkylating agent (1.10 equiv)
was added followed by the addition of pyridine (5.00 equiv). The re-
action mixture was stirred for 18–24 h. Progression of the reaction
was followed by taking a small aliquot of the reaction suspension,
adding 14% aq NH4OH and extracting with CH2Cl2; the organic
layer was analyzed by TLC and GC-MS. Upon reaction completion,
the reaction mixture was diluted with 14% aq NH4OH to obtain a
concentration of about 0.10 M and left under agitation for 1 h. The
reaction suspension was then filtered; the solid was washed copi-
ously with H2O and dried under reduced pressure. The resulting
solid was directly used for chemical characterization without any
further purification.
1-Benzyl-4-(3-methoxyphenyl)-1H-1,2,3-triazole (2d)
Average yield: 74%; greenish solid; mp 76–77 °C; Rf = 0.24
(EtOAc–hexanes, 3:7).
1H NMR (400 MHz, CDCl3): d = 7.65 (s, 1 H), 7.47–7.21 (m, 8 H),
6.90–6.83 (m, 1 H), 5.56 (s, 2 H), 3.85 (s, 3 H).
13C NMR (101 MHz, CDCl3): d = 160.2, 148.3, 134.9, 132.1, 130.1,
129.4, 129.0, 128.3, 120.0, 118.3, 114.6, 110.9, 55.6, 54.5.
LRMS (EI, 70 eV): m/z = 265 [M+], 262, 236, 206, 146, 119, 104,
91.
HRMS (EI, 70 eV): m/z calcd for C16H15N3O: 265.1215; found:
265.1221.
The compound characterization is in agreement with that previously
reported.28
Mixture of 1-Benzyl-4-phenyl-1H-1,2,3-triazole (2a) and 1-Ben-
zyl-5-phenyl-1H-1,2,3-triazole (3a)
Average yield: 61%; white solid; Rf = 0.18 (EtOAc–hexanes, 2:8).
1H NMR (300 MHz, CDCl3) (1,5-regioisomer 3a): d = 7.94 (s),
7.84–7.74 (m), 7.45–7.35 (m), 5.58 (s), 5.56 (s).
1H NMR (300 MHz, CDCl3) (1,4-regioisomer 2a): d = 7.84–7.74
(m), 7.66 (s), 7.45–7.35 (m), 5.58 (s).
4-(1-Benzyl-1H-1,2,3-triazol-4-yl)-N,N-dimethylaniline (2e)
Average yield: 72%; brown solid; mp 172 °C (dec); Rf = 0.23
(EtOAc–hexanes, 3:7).
1H NMR (400 MHz, CDCl3): d = 7.60 (d, J = 8.9 Hz, 2 H), 7.46 (s,
1 H), 7.37–7.16 (m, 5 H), 6.67 (d, J = 8.9 Hz, 2 H), 5.48 (s, 2 H),
2.91 (s, 6 H).
The compound characterization of both isomers is in agreement
with that previously reported.27 For the characterization of isolated
2a, see the following.
13C NMR (101 MHz, CDCl3): d = 150.5, 148.9, 135.1, 129.2, 128.8,
128.1, 126.8, 118.9, 118.1, 112.5, 54.2, 40.6.
LRMS (EI, 70 eV): m/z = 278 [M+], 249, 173, 159, 116, 91.
1-Benzyl-4-phenyl-1H-1,2,3-triazole (2a)
White solid; mp 124–125 °C (Lit.14 128–129 °C); Rf = 0.18
(EtOAc–hexanes, 2:8).
1H NMR (300 MHz, CDCl3): d = 7.80 (d, J = 7.1 Hz, 2 H), 7.66 (s,
1 H), 7.45–7.27 (m, 8 H), 5.56 (s, 2 H).
13C NMR (101 MHz, CDCl3): d = 148.4, 134.9, 130.8, 129.4, 129.0,
129.0, 128.4, 128.3, 125.9, 119.8, 54.4.
LRMS (EI, 70 eV): m/z = 235 [M+], 206, 180, 116, 104, 91, 89.
HRMS (EI, 70 eV): m/z calcd for C17H18N4: 278.1531; found:
278.1537.
1-Benzyl-4-(4-bromophenyl)-1H-1,2,3-triazole (2f)
Average yield: 88%; beige solid; mp 140–142 °C (Lit.14 147–
148 °C); Rf = 0.12 (EtOAc–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 7.69–7.64 (m, 3 H), 7.54–7.50 (m,
2 H), 7.46–7.27 (m, 5 H), 5.57 (s, 2 H).
13C NMR (101 MHz, CDCl3): d = 147.3, 134.6, 132.1, 129.6, 129.3,
129.0, 128.3, 127.3, 122.2, 119.7, 54.5.
LRMS (EI, 70 eV): m/z = 313 [M+], 284, 206, 194, 179, 130, 91.
HRMS (EI, 70 eV): m/z calcd for C15H13N3: 235.1109; found:
235.1110.
The compound characterization is in agreement with that previously
reported.27
HRMS (EI, 70 eV): m/z calcd for C15H12BrN3: 313.0215; found:
313.0221.
4-(1-Benzyl-1H-1,2,3-triazol-4-yl)phenol (2b)
Average yield: 61%; beige solid; mp 184–186 °C; Rf = 0.11
(EtOAc–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 7.60 (d, J = 8.7 Hz, 2 H), 7.50 (s,
1 H), 7.36–7.20 (m, 5 H), 6.81 (d, J = 8.7 Hz, 2 H), 5.50 (s, 2 H).
13C NMR (101 MHz, CD3CN): d = 158.0, 148.5, 137.0, 129.9,
129.3, 128.9, 127.8, 123.7, 120.6, 116.6, 54.5.
The compound characterization is in agreement with that previously
reported.14
1-Benzyl-4-(2,4-difluorophenyl)-1H-1,2,3-triazole (2g)
Average yield: 84%; yellow solid; mp 124–125 °C; Rf = 0.30
(EtOAc–hexanes, 4:6).
1H NMR (400 MHz, CDCl3): d = 8.28 (td, J = 8.7, 6.5 Hz, 1 H),
7.81 (d, J = 3.7 Hz, 1 H), 7.42–7.35 (m, 3 H), 7.33–7.28 (m, 2 H),
6.99 (dddd, J = 8.9, 8.0, 2.5, 1.0 Hz, 1 H), 6.87 (ddd, J = 11.2, 8.8,
2.5 Hz, 1 H), 5.59 (s, 2 H).
LRMS (EI, 70 eV): m/z = 251 [M+], 222, 195, 146, 132, 105, 91, 77.
HRMS (EI, 70 eV): m/z calcd for C15H13N3O: 251.1059; found:
251.1055.
13C NMR (101 MHz, CDCl3): d = 163.9 (d, J = 12.1 Hz), 161.0 (dd,
J = 84.7, 11.9 Hz), 158.1 (d, J = 11.8 Hz), 141.2 (s), 134.8 (s), 129.4
(s), 129.0–128.9 (m), 128.2 (s), 122.4 (d, J = 12.1 Hz), 115.2 (dd,
J = 13.2, 3.8 Hz), 112.2 (dd, J = 21.3, 3.5 Hz), 104.3 (t, J = 25.7
Hz), 54.5 (s).
1-Benzyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (2c)
Average yield: 61%; white solid; mp 139–141 °C (Lit.14 143–
144 °C); Rf = 0.10 (EtOAc–hexanes, 1:9).
1H NMR (400 MHz, CDCl3): d = 7.72 (d, J = 8.9 Hz, 2 H), 7.57 (s,
1 H), 7.45–7.22 (m, 5 H), 6.93 (d, J = 8.9 Hz, 2 H), 5.56 (s, 2 H),
3.83 (s, 3 H).
LRMS (EI, 70 eV): m/z = 271 [M+], 242, 195, 152, 125, 104, 91.
HRMS (EI, 70 eV): m/z calcd for C15H11F2N3: 271.0921; found:
271.0923.
13C NMR (101 MHz, CDCl3): d = 159.8, 148.3, 135.0, 129.4,
129.0, 128.3, 127.2, 123.5, 118.9, 114.4, 55.5, 54.4.
LRMS (EI, 70 eV): m/z = 265 [M+], 236, 179, 146, 119, 91.
Methyl 4-(1-Benzyl-1H-1,2,3-triazol-4-yl)benzoate (2h)
Average yield: 76%; yellowish solid; mp 147 °C (dec); Rf = 0.40
(EtOAc–hexanes, 4:6).
HRMS (EI, 70 eV): m/z calcd for C16H15N3O: 265.1215; found:
265.1216.
The compound characterization is in agreement with that previously
reported.14,27
Synthesis 2011, No. 22, 3604–3611 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
One-Pot Click Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
LRMS (EI, 70 eV): m/z = 249 [M+], 220, 130, 91.
3609
1H NMR (400 MHz, CDCl3): d = 8.06 (d, J = 8.5 Hz, 2 H), 7.86 (d,
J = 8.6 Hz, 2 H), 7.75 (s, 1 H), 7.43–7.28 (m, 5 H), 5.58 (s, 2 H),
3.91 (s, 3 H).
13C NMR (101 MHz, CDCl3): d = 167.0, 147.4, 135.1, 134.7, 130.4,
129.8, 129.5, 129.1, 128.4, 125.7, 120.7, 120.6, 54.6, 52.4.
HRMS (EI, 70 eV): m/z calcd for C16H15N3: 249.1266; found:
249.1269.
The compound characterization is in agreement with that previously
reported.13c
LRMS (EI, 70 eV): m/z = 293 [M+], 264, 206, 174, 147, 129, 104,
91.
1-Benzyl-4-(1-naphthyl)-1H-1,2,3-triazole (2m)
Average yield: 76%; greenish solid; mp 89–90 °C (Lit.14 74–
75 °C); Rf = 0.16 (EtOAc–hexanes, 3:7).
1H NMR (400 MHz, CDCl3): d = 8.42–8.29 (m, 1 H), 7.94–7.82 (m,
2 H), 7.73 (s, 1 H), 7.69 (dd, J = 7.1, 1.2 Hz, 1 H), 7.56–7.32 (m, 8
H), 5.66 (s, 2 H).
HRMS (EI, 70 eV): m/z calcd for C17H15N3O2: 293.1164; found:
293.1166.
The compound characterization is in agreement with that previously
reported.29
1-Benzyl-4-(4-nitrophenyl)-1H-1,2,3-triazole (2i)
Average yield: 77%; white solid; mp 169–171 °C (Lit.14 167–
169 °C); Rf = 0.16 (EtOAc–hexanes, 3:7).
13C NMR (101 MHz, CDCl3): d = 147.5, 134.8, 134.0, 131.2, 129.3,
129.0, 128.9, 128.6, 128.3, 128.1, 127.3, 126.8, 126.1, 125.5, 125.4,
122.6, 54.4.
1H NMR (400 MHz, CDCl3): d = 8.25 (d, J = 8.8 Hz, 2 H), 7.96 (d,
J = 8.8 Hz, 2 H), 7.81 (s, 1 H), 7.46–7.29 (m, 5 H), 5.60 (s, 2 H).
13C NMR (101 MHz, CDCl3): d = 147.4, 146.1, 136.9, 134.3, 129.4,
129.2, 128.3, 126.2, 124.4, 121.0, 54.6.
LRMS (EI, 70 eV): m/z = 285 [M+], 256, 229, 166, 91.
HRMS (EI, 70 eV): m/z calcd for C19H15N3: 285.1266; found:
285.1275.
The compound characterization is in agreement with that previously
reported.14
LRMS (EI, 70 eV): m/z = 280 [M+], 251, 179, 161, 104, 91.
HRMS (EI, 70 eV): m/z calcd for C15H12N4O2: 280.0960; found:
280.0965.
2-(1-Benzyl-1H-1,2,3-triazol-4-yl)pyridine (2n)
Average yield: 57%; beige solid; mp 115–116 °C (Lit.14 112–
113 °C); Rf = 0.13 (EtOAc–hexanes, 4:6).
1H NMR (400 MHz, CDCl3): d = 8.52 (d, J = 5.5 Hz, 1 H), 8.16 (dt,
J = 8.0, 1.0 Hz, 1 H), 8.03 (s, 1 H), 7.75 (td, J = 7.8, 1.8 Hz, 1 H),
7.42–7.28 (m, 5 H), 7.19 (ddd, J = 7.5, 4.9, 1.2 Hz, 1 H), 5.57 (s, 2
H).
13C NMR (101 MHz, CDCl3): d = 150.5, 149.6, 149.0, 137.1, 134.5,
129.4, 129.1, 128.6, 123.1, 122.1, 120.45, 54.6.
LRMS (EI, 70 eV): m/z = 236 [M+], 207, 195, 180, 160, 117, 91.
The compound characterization is in agreement with that previously
reported.14
1-Benzyl-4-(3-nitrophenyl)-1H-1,2,3-triazole (2j)
Average yield: 62%; beige solid; mp 133–136 °C; Rf = 0.17
(EtOAc–hexanes, 3:7).
1H NMR (400 MHz, CDCl3): d = 8.55 (s, 1 H), 8.18 (d, J = 7.8 Hz,
1 H), 8.12 (dd, J = 8.2, 1.6 Hz, 1 H), 7.85 (s, 1 H), 7.56 (t, J = 8.0
Hz, 1 H), 7.42–7.29 (m, 5 H), 5.60 (s, 2 H).
13C NMR (101 MHz, CDCl3): d = 148.6, 134.3, 132.4, 131.5, 129.9,
129.3, 129.1, 128.3, 122.8, 120.6, 120.5, 54.5.
HRMS (EI, 70 eV): m/z calcd for C14H12N4: 236.1062; found:
236.1063.
LRMS (EI, 70 eV): m/z = 280 [M+], 251, 205, 179, 161, 115, 91.
The compound characterization is in agreement with that previously
reported.14,30
HRMS (EI, 70 eV): m/z calcd for C15H12N4O2: 280.0960; found:
280.0965.
Mixture of 1-Benzyl-4-(2-thienyl)-1H-1,2,3-triazole (2o) and
1-Benzyl-5-(2-thienyl)-1H-1,2,3-triazole (3o)
1-Benzyl-4-(2-nitrophenyl)-1H-1,2,3-triazole (2k)
Average yield: 75%; beige solid; mp 106–107 °C (Lit.27 110–
112 °C); Rf = 0.17 (EtOAc–hexanes, 3:7).
1H NMR (400 MHz, CDCl3): d = 7.97 (d, J = 7.9 Hz, 1 H), 7.77 (d,
J = 8.1 Hz, 1 H), 7.74 (s, 1 H), 7.61 (t, J = 7.7 Hz, 1 H), 7.45 (t,
J = 7.8 Hz, 1 H), 7.40–7.24 (m, 5 H), 5.56 (s, 2 H).
13C NMR (101 MHz, CDCl3): d = 148.4, 142.7, 134.6, 132.8, 131.3,
129.4, 129.2, 129.1, 128.3, 124.9, 124.3, 123.2, 54.5.
LRMS (EI, 70 eV): m/z = 280 [M+], 165, 134, 104, 91.
Average yield: 65%; off-white solid; mp 120–121 °C (Lit.14 120–
122 °C); Rf = 0.24 (EtOAc–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 7.93 (s, 0.3 H), 7.57 (s, 1 H), 7.38
(t, J = 6.0 Hz, 4 H), 7.35–7.24 (m, 5 H), 7.09–7.01 (m, 1 H), 5.56 (s,
3 H).
13C NMR (101 MHz, CDCl3): d = 143.5, 134.7, 134.5, 133.1, 129.4,
129.1, 129.1, 128.5, 128.3, 127.8, 125.3, 124.4, 120.8, 119.2, 54.5.
LRMS (EI, 70 eV): m/z = 241 [M+], 212, 180, 122, 91.
HRMS (EI, 70 eV): m/z calcd for C13H11N3S: 241.0674; found:
241.0682.
HRMS (EI, 70 eV): m/z calcd for C15H12N4O2: 280.0960; found:
280.0965.
The characterization data of the 1,4-regioisomer matched those giv-
en in the literature,14 but no data concerning the 1,5-regioisomer
could be found.
The compound characterization is in agreement with that previously
reported.27
1-Benzyl-4-o-tolyl-1H-1,2,3-triazole (2l)
Average yield: 86%; beige solid; mp 108–109 °C; Rf = 0.27
(EtOAc–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 7.80–7.68 (m, 1 H), 7.57 (s, 1 H),
7.38 (s, 3 H), 7.34–7.28 (m, 2 H), 7.25 (d, J = 2.8 Hz, 3 H), 5.60 (s,
2 H), 2.43 (s, 3 H).
2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-5-bromopyridine (2p)
Average yield: 91%; beige solid; mp 149–150 °C; Rf = 0.05
(EtOAc–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 8.70 (dd, J = 2.5, 0.7 Hz, 1 H),
8.04 (dd, J = 8.3, 2.5 Hz, 1 H), 7.74 (s, 1 H), 7.53 (dd, J = 8.3, 0.7
Hz, 1 H), 7.45–7.28 (m, 5 H), 5.59 (s, 2 H).
13C NMR (101 MHz, CDCl3): d = 147.8, 135.7, 135.0, 131.1, 130.1,
129.4, 129.1, 129.0, 128.4, 128.2, 126.3, 121.9, 54.4, 21.6.
13C NMR (101 MHz, CDCl3): d = 147.3, 144.3, 141.5, 135.7, 134.4,
129.5, 129.3, 128.5, 128.4, 126.3, 120.2, 54.7.
Synthesis 2011, No. 22, 3604–3611 © Thieme Stuttgart · New York

3610
S. Ladouceur et al.
PRACTICAL SYNTHETIC PROCEDURES
LRMS (EI, 70 eV): m/z = 314 [M+], 285, 195, 180, 130, 104, 91.
1-Hexyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (2v)
The solvent mixture used was MeOH–H2O–THF (1:1:1), at the
same concentration as that indicated in the general procedure.
HRMS (EI, 70 eV): m/z calcd for C14H11BrN4: 314.0167; found:
314.0172.
Average yield: 68%; beige solid; mp 90–92 °C; Rf = 0.10 (EtOAc–
2,5-Bis(1-benzyl-1H-1,2,3-triazol-4-yl)pyridine (2q)
hexanes, 2:8).
The solvent mixture used was MeOH–H2O–THF (1:1:1), at the
same concentration as that indicated in the general procedure.
1H NMR (400 MHz, CDCl3): d = 7.75 (d, J = 8.9 Hz, 2 H), 7.66 (s,
1 H), 6.95 (d, J = 8.9 Hz, 2 H), 4.36 (t, J = 7.2 Hz, 2 H), 3.83 (s, 3
H), 2.01–1.81 (m, 2 H), 1.46–1.15 (m, 6 H), 1.02–0.71 (m, 3 H).
Average yield: 96%; beige solid; mp 253 °C (dec); Rf = 0.28
(EtOAc–hexanes, 2:8).
13C NMR (101 MHz, CDCl3): d = 159.7, 147.8, 127.2, 123.7, 118.8,
1H NMR (400 MHz, CDCl3): d = 8.95 (s, 1 H), 8.19 (q, J = 8.3 Hz,
2 H), 8.05 (s, 1 H), 7.74 (s, 1 H), 7.49–7.28 (m, 10 H), 5.70–5.48
(m, 4 H).
13C NMR (101 MHz, CDCl3): d = 149.9, 146.8, 145.5, 134.5, 134.0,
129.4, 129.1, 129.0, 128.5, 128.3, 122.2, 120.3, 120.0, 55.6.
114.4, 55.6, 50.6, 31.4, 30.6, 26.4, 22.7, 14.2.
LRMS (EI, 70 eV): m/z = 259 [M+], 204, 175, 147, 121, 89.
HRMS (EI, 70 eV): m/z calcd for C15H21N3O: 259.1685; found:
259.1679.
LRMS (EI, 70 eV): m/z = 393 [M+], 336, 309, 274, 246, 231, 141,
127, 91.
6-[4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]hexan-1-ol (2w)
The solvent mixture used was MeOH–H2O–THF (1:1:1), at the
same concentration as that indicated in the general procedure.
HRMS (EI, 70 eV): m/z calcd for C23H19N7: 393.1702; found:
393.1698.
Average yield: 62%; yellow solid; mp 117–118 °C; Rf = 0.05
(EtOAc–hexanes, 2:8).
5-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2,2¢-bipyridine (2r)
Average yield: 70%; light brown solid; mp 197–199 °C (Lit.31 197–
198 °C); Rf = 0.70 (MeOH–CH2Cl2, 1:9).
1H NMR (300 MHz, CDCl3): d = 9.07 (s, 1 H), 8.69 (s, 2 H), 8.43
(s, 1 H), 8.27 (d, J = 8.1 Hz, 1 H), 7.93–7.71 (m, 2 H), 7.54–7.26
(m, 6 H), 5.61 (s, 2 H).
13C NMR (101 MHz, CDCl3): d = 155.4, 152.3, 149.4, 145.4, 140.1,
137.1, 134.5, 133.8, 129.3, 129.0, 128.2, 124.2, 121.6, 120.4, 119.3,
54.5.
1H NMR (400 MHz, CDCl3): d = 7.75 (d, J = 8.4 Hz, 2 H), 7.66 (s,
1 H), 6.95 (d, J = 8.4 Hz, 2 H), 4.38 (t, J = 7.1 Hz, 2 H), 3.84 (s, 3
H), 3.63 (dd, J = 11.9, 6.0 Hz, 2 H), 2.02–1.87 (m, 2 H), 1.62–1.29
(m, 6 H).
13C NMR (101 MHz, CDCl3): d = 159.8, 147.8, 127.2, 123.6, 118.9,
114.4, 62.8, 55.6, 50.5, 32.6, 30.5, 26.4, 25.4.
LRMS (EI, 70 eV): m/z = 275 [M+], 202, 175, 147, 132, 112, 89.
HRMS (EI, 70 eV): m/z calcd for C15H21N3O2: 275.1634; found:
275.1639.
LRMS (EI, 70 eV): m/z = 313 [M+], 284, 208, 194, 140, 104, 91.
HRMS (EI, 70 eV): m/z calcd for C19H15N5: 313.1327; found:
313.1334.
1-Allyl-4-(4-methoxyphenyl)-1H-1,2,3-triazole (2x)
Average yield: 66%; beige solid; mp 89–91 °C (Lit.32 88–89 °C);
Rf = 0.14 (EtOAc–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 7.85 (d, J = 8.9 Hz, 2 H), 7.78 (s,
1 H), 7.06 (d, J = 8.9 Hz, 2 H), 6.16 (ddt, J = 16.9, 10.2, 6.1 Hz, 1
H), 5.52–5.36 (m, 2 H), 5.11 (dt, J = 6.1, 1.4 Hz, 2 H), 3.94 (s, 3 H).
The compound characterization is in agreement with that previously
reported.31
5,5¢-Bis(1-benzyl-1H-1,2,3-triazol-4-yl)-2,2¢-bipyridine (2s)
The solvent mixture used was MeOH–H2O–THF (1:1:1), at the
same concentration as that indicated in the general procedure.
13C NMR (101 MHz, CDCl3): d = 159.8, 148.1, 131.6, 127.2, 123.6,
120.4, 118.8, 114.4, 55.6, 53.0.
Average yield: 80%; beige solid; mp >380 °C; Rf = 0.68 (MeOH–
CH2Cl2, 1:9).
1H NMR (300 MHz, CDCl3): d = 9.06 (s, 2 H), 8.47 (d, J = 8.0 Hz,
2 H), 8.28 (d, J = 7.8 Hz, 2 H), 7.80 (s, 2 H), 7.49–7.30 (m, 10 H),
5.62 (s, 4 H).
13C NMR (75 MHz, CDCl3): d = 152.4, 146.7, 140.2, 134.0, 129.5,
129.2, 128.3, 121.6, 120.5, 120.2, 81.6, 54.6.
LRMS (EI, 70 eV): m/z = 470 [M+], 413, 323, 232, 91.
LRMS (EI, 70 eV): m/z = 215 [M+], 186, 146, 132, 119, 75.
HRMS (EI, 70 eV): m/z calcd for C12H13N3O: 215.1059; found:
215.1063.
The compound characterization is in agreement with that previously
reported.32
1,3,5-Tris{[4-(2,4-difluorophenyl)-1H-1,2,3-triazol-1-yl]meth-
yl}benzene (2y)
The solvent mixture used was MeOH–H2O–THF (1:1:1), at the
same concentration as that indicated in the general procedure.
HRMS (EI, 70 eV): m/z calcd for C28H22N8: 470.1967; found:
470.1973.
Average yield: 82%; yellow solid; mp 130 °C (dec); Rf = 0.14
4-(4-M ethoxyphenyl)-1-methyl-1H-1,2,3-triazole (2t)
Average yield: 41%; beige solid; mp 150–151 °C; Rf = 0.27
(EtOAc–hexanes, 2:8).
1H NMR (400 MHz, CDCl3): d = 7.73 (d, J = 8.9 Hz, 2 H), 7.65 (s,
1 H), 6.95 (d, J = 8.9 Hz, 2 H), 4.11 (s, 3 H), 3.83 (s, 3 H).
13C NMR (101 MHz, CDCl3): d = 159.8, 148.1, 127.2, 123.5, 120.0,
114.5, 55.6, 37.0.
(EtOAc–hexanes, 4:6).
1H NMR (400 MHz, CDCl3): d = 8.25 (dd, J = 15.2, 8.6 Hz, 3 H),
7.82 (d, J = 3.5 Hz, 3 H), 7.22 (d, J = 28.5 Hz, 3 H), 6.99 (t, J = 7.3
Hz, 3 H), 6.84 (t, J = 8.6 Hz, 3 H), 5.56 (s, 6 H).
13C NMR (101 MHz, CDCl3): d = 162.8 (dd, J = 250, 12.4 Hz),
159.4 (dd, J = 251, 12.0 Hz), 141.5 (s), 137.3 (s), 129.6–128.3 (m),
127.5 (s), 122.5 (dd, J = 12.4, 8.4 Hz), 114.9 (dd, J = 13.1, 3.9 Hz),
112.3 (d, J = 21.3 Hz), 104.3 (td, J = 25.4, 5.8 Hz), 53.6 (s).
LRMS (EI, 70 eV): m/z = 189 [M+], 146, 130, 91.
LRMS (EI, 70 eV): m/z = 657 [M+], 629, 478, 448, 421, 297, 268,
152, 125, 115, 91.
HRMS (EI, 70 eV): m/z calcd for C10H11N3O: 189.0902; found:
189.0906.
HRMS (EI, 70 eV): m/z calcd for C33H21F6N9: 657.1824; found:
657.1837.
Synthesis 2011, No. 22, 3604–3611 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
One-Pot Click Synthesis of 1,4-Disubstituted 1,2,3-Triazoles
3611
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis; general
procedures and characterization of the (arylethynyl)trimethyl-
silanes and other relevant intermediates, as well as copies of 1H and
13C NMR spectra for all new compounds and all triazoles, are in-
cluded.
N.; Lockwood, C.; Rice, C. R.; Elliott, P. I. P. Dalton Trans.
2011, 40, 7610. (k) Kilpin, K. J.; Gavey, E. L.; McAdam, C.
J.; Anderson, C. B.; Lind, S. J.; Keep, C. C.; Gordon, K. C.;
Crowley, J. D. Inorg. Chem. 2011, 50, 6334. (l) Fleischel,
O.; Wu, N.; Petitjean, A. Chem. Commun. 2010, 46, 8454.
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A.; González, L.; Schubert, U. S. Organometallics 2009, 28,
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Acknowledgment
E.Z.-C. acknowledges CFI (Canadian Foundation for Innovation),
NSERC (Natural Sciences and Engineering Research Council of
Canada), FQRNT (Le Fonds québécois de la recherche sur la nature
et les technologies) and the Université de Sherbrooke for financial
support. S.L. acknowledges the Université de Sherbrooke for an in-
stitutional scholarship.
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absence of pyridine, after 24 hours only a 20% deprotection
was observed with a corresponding 20% conversion into 2g,
as determined by GC-MS. In the absence of K2CO3,
deprotection of 1g was completely arrested.
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Synthesis 2011, No. 22, 3604–3611 © Thieme Stuttgart · New York