Synthesis and NMR analysis of 1,4-disubstituted 1,2,3-triazoles tethered to pyridine, pyrimidine, and pyrazine rings

Article abstract of DOI:10.1002/ejoc.201403100

A combinatorial modular approach based on the "click" copper(I)-catalysed azide-alkyne cycloaddition reaction was used to prepare a library of selected 1,4-disubstituted 1,2,3-triazoles differently functionalized with heteroaryl groups including pyridine,

Full text of DOI:10.1002/ejoc.201403100

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FULL PAPER
DOI: 10.1002/ejoc.201403100
Synthesis and NMR Analysis of 1,4-Disubstituted 1,2,3-Triazoles Tethered to
Pyridine, Pyrimidine, and Pyrazine Rings
[a]
[a]
[a]
ˇ
ˇ
Aljosa Bolje, Damijana Urankar, and Janez Kosmrlj*
Dedicated to Professor Marijan Kocˇevar on his 65th birthday
Keywords: Nitrogen heterocycles / Click chemistry / Ligand design / NMR spectroscopy
A combinatorial modular approach based on the “click” cop-
per(I)-catalysed azide–alkyne cycloaddition reaction was
used to prepare a library of selected 1,4-disubstituted 1,2,3-
triazoles differently functionalized with heteroaryl groups in-
cluding pyridine, pyrimidine, and pyrazine. Three different
copper(I) sources, i.e., CuSO4/sodium ascorbate, CuBr(PPh3)3,
and (CuOTf)2·C6H6 were used to promote the coupling reac-
tions of a range of aryl, heteroaryl, and heteroarylmethyl
azides with alkyne “click” partners. As the target heteroaryl
triazoles were designed to serve as advanced ligands or li-
gand precursors for metal coordination, they were fully char-
acterized by 1H, 13C, and 15N NMR spectroscopy. The reso-
nances were assigned on the basis of 1D and 2D NMR ex-
periments. 1H–15N gs-HMBC was used as a practical tool to
determine 15N NMR chemical shifts at the natural abundance
level of the 15N isotope.
compounds can easily be transformed into selectively alkyl-
ated pyridine-appended triazolium cations,[10] relevant for
the development of organic and organometallic catalyst
precursors, new materials, and target-specific ionic liquids,
to name just a few possible applications.[11]
Introduction
Although the thermal azide–alkyne cycloaddition to
transform an organic azide 1 and a terminal acetylene 2
into a 1,2,3-triazole ring has been known for more than a
century, the number of applications for this heterocycle has
not increased until recently.[1] This changed dramatically
with the discovery of the copper-catalysed azide–alkyne cy-
cloaddition to produce the triazole ring in a reaction that
meets all the criteria of “click” chemistry (CuAAC,
Scheme 1).[2,3] Since then, the so called “click” triazole has
found widespread application in almost every research area
of chemical, biochemical, and materials sciences.[4] With no
doubt, “there is more function to the 1,2,3-triazole unit than
first meets the eye.”[5] In coordination chemistry, for exam-
ple, architectures containing this heterocycle have been de-
Scheme 1. CuAAC reaction to produce “click” triazoles 3–6 (see
Figure 1).
In this paper, we report the preparation of homologous
veloped as monodentate and polydentate nitrogen ligands. and isomeric heteroaryl (pyridyl, pyrimidyl, and pyrazinyl)
Special attention has been given to (2-pyridyl)- and more appended 1,2,3-triazole scaffolds, more specifically, het-
flexible (2-picolyl)-1,2,3-triazoles,[6,7] because they are eroaryl 3–4 and heteroarylmethyl 5–6 substituted 1,2,3-tri-
viewed as surrogates for the well-known 2,2Ј-bipyridine[8] azoles, as shown in Figure 1. These compounds will serve
and bis(heterocycle)methane ligands, respectively.[9] Very re- as ligands or ligand precursors for the synthesis of five- and
cently, we have shown that in just a couple of steps these six-membered metallacycles with bidentate N,N and
N,tzNHC[12] coordination environments. The compounds
will have tuneable properties so will be useful in research
towards new homogeneous catalysts and metal-based phar-
[a] Faculty of Chemistry and Chemical Technology, University of
macologically relevant agents. Beyond the pyridyl–triazole
Ljubljana,
scaffold, the potential of the pyrimidyl- and pyrazinyl-con-
taining derivatives comes from an additional ring-nitrogen
atom, which should change their properties in a dramatic
way.
Asˇkercˇeva 5, 1000 Ljubljana, Slovenia
E-mail: janez.kosmrlj@fkkt.uni-lj.si
http://www.fkkt.uni-lj.si/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403100.
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A. Bolje, D. Urankar, J. Kosˇmrlj
FULL PAPER
Figure 1. Diversity of pyridine-, pyrazine-, and pyrimidine-functionalized 1,2,3-triazoles 3–6 from this investigation (top) that serve as
precursors for five- and six-membered metallacycles with N,N (middle) or N,tzNHC (bottom) coordination environments around the metal
centre M.
(CuAAC) shown in Scheme 1 using the building blocks
shown in Figure 2.
Results and Discussion
All the 1,4-disubstituted 1,2,3-triazole members 3–6 (Fig-
2-Azidopyridine (1A), required for the preparation of 4-
ure 1) of the library described in this paper were accessed aryl-1-(2-pyridyl)-1,2,3-triazoles 3 (Figure 1), was obtained
through the copper-catalysed azide–alkyne cycloaddition by the substitution reaction of 2-bromopyridine with so-
Figure 2. Building blocks for triazole library synthesis. The same capital and small letter denotes the same substituent at the azide and
acetylene, respectively.
2
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1,2,3-Triazoles Tethered to Heterocycles
dium azide. It exists in a tetrazolyl form as tetrazolo[1,5-a]- sults to CuBr(PPh3)3 in terms of reaction time, by-product
pyridine (1AЈ; Scheme 2).[13] The azide–tetrazole equilib- formation, and yield of the desired triazoles (Table 1, en-
rium, which can retard the CuAAC reaction, depends on tries 3 and 8).
the solvent polarity and temperature.[14,15–18] As the pro-
2-Azidopyrimidine (1B), prepared by the literature pro-
portion of the azido isomer increases with decreasing sol- cedure from 2-hydrazinopyrimidine, also undergoes the
vent dielectric constant and increasing temperature, we azide–tetrazole equilibrium with tetrazolo[1,5-a]pyrimidine
chose to conduct the CuAAC reaction between 2-azidopyr- (1BЈ) as the prevailing isomer (Scheme 2).[21] Thus, as dis-
idine (1A) [i.e., tetrazolo[1,5-a]pyridine (1AЈ)] and phenyl- cussed above for 2-azidopyridine (1A), and with a similar
acetylene derivatives 2(f–k,m,n) with CuBr(PPh3)3 in re- efficiency, 2-azidopyrimidine (1B) [i.e., tetrazolo[1,5-a]pyr-
fluxing toluene. The desired 4-aryl-1-(2-pyridyl)-1,2,3-tri- imidine (1BЈ)] was ligated with phenylacetylene derivatives
azoles [i.e., 3A(f–k,m,n)] were obtained in moderate to good 2(f,m,n) to give 4-aryl-1-(2-pyrimidyl)-1,2,3-triazoles
yields (Table 1, entries 1, 2, and 4–7). In part, this is a result 3B(f,m,n) by using CuBr(PPh3)3 or (CuOTf)2·C6H6 in boil-
of the prolonged heating, which leads to the formation of ing toluene (Table 1, entries 9, 10, and 11, respectively).
some by-products. For example, in some cases, analysis of
Isomeric 1-aryl-4-(2-pyridyl)-1,2,3-triazoles 4 (Figure 1)
the crude reaction mixtures indicated the presence of 1,4- were conveniently prepared by the CuAAC reaction of aryl
diphenylbuta-1,3-diyne and 1,5-disubstituted 1,2,3-triazole azides 1(F–K) with 2-ethynylpyridine (2a) as shown in
derivatives. The former are the result of copper-mediated Table 2. For these reactions, a combination of copper(II)
dimerization[19] of the phenylacetylene reactants (i.e., 2), sulfate and sodium ascorbate pentahydrate was used as the
and the latter came from a competitive thermally induced source of copper(I). The reactions were carried out in wet
azide–alkyne cycloaddition.[20] The low isolated yields of methanol at room temperature, and gave triazole products
triazoles 3 are also a result of their low solubility, which 4 in good to excellent yields. All aryl azides 1(F–K) used in
hampers their isolation and purification.
this work were prepared by standard one-pot diazotization
of the appropriate anilines and subsequent SNAr displace-
ments of the diazonium group with sodium azide.[22]
Table 2. Synthesis of 1-aryl-4-(2-pyridyl)-1,2,3-triazoles 4.
Scheme 2. Azide–tetrazole equilibrium of 1A and 1B.
Table 1. Synthesis of 4-aryl-1-(heteroaryl)-1,2,3-triazoles 3.
Entry
Azide 1
R
Product 4
Yield [%][a]
1
2
3
4
5
6
1F
1G
1H
1I
H
4Fa
4Ga
4Ha
4Ia
4Ja
4Ka
83
70
90
85
81
82
Me
OMe
CN
CF3
Br
1J
1K
[a] Yield of isolated pure product.
Entry
1
2
R
H
Cat. [mol-%]
Time [h]
3
Yield [%][a]
1
2
3
4
5
6
7
8
1A
2f
CuBr(PPh3)3, 4
CuBr(PPh3)3, 4
8
7
25
16
23
8
17
17
31[b]
17
55[b]
3Af
3Ag
3Ah
3Ai
62
55
62
52
79
74
71
71
58
43
57
Eight 4-aryl-1-(2-picolyl)-1,2,3-triazoles 5 were prepared
by the CuAAC reaction between 2-picolyl azide (1C) and
the appropriate commercially available phenyl acetylenes
[i.e., 2(f–j,l–n)]. The results are summarized in Table 3, en-
tries 1–8. 2-Picolyl azide (1C) was obtained through the nu-
cleophilic substitution of 2-(chloromethyl)pyridine hydro-
chloride with sodium azide.[23] Although several effective
triazole-forming protocols and conditions have been devel-
oped to date,[24] we chose to conduct this CuAAC reaction
neat, with CuBr(PPh3)3 as precatalyst. The selection of this
copper(I) source was based on its reportedly good perform-
1A 2g Me
1A 2h OMe (CuOTf)2·C6H6, 5
1A
1A
1A 2k Br
1A 2m NO2 CuBr(PPh3)3, 4
1A 2n NMe2 (CuOTf)2·C6H6, 2
2i CN CuBr(PPh3)3, 4
2j CF3 CuBr(PPh3)3, 4
3Aj
CuBr(PPh3)3, 4
3Ak
3Am
3An
3Bf
3Bm
3Bn
9
10
11
1B
2f
H
CuBr(PPh3)3, 3
1B 2m NO2 CuBr(PPh3)3, 3
1B 2n NMe2 (CuOTf)2·C6H6, 2
[a] Yield of isolated pure product. [b] For details, see Exp. Sect.
Another copper(I) source, (CuOTf)2·C6H6, has been re- ance as well as its stability towards the oxygen in air.[25] In
ported to be superior for the CuAAC ligation of tetraz- contrast to the reactions with many other commonly used
olo[1,5-a]pyridines.[16] In our hands, for the preparation of copper(I) and copper(II) compounds, the CuAAC reaction
3Ah and 3An, this copper precatalyst gave comparable re- with CuBr(PPh3)3 can be conveniently conducted in an
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A. Bolje, D. Urankar, J. Kosˇmrlj
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open vessel, with no need for exclusion of oxygen, and with- argyl bromide, nor by the substitution of 2-chloromethyl-
out the use of sacrificial reducing reagents. Thus, by using piridine with sodium acetylide.[26] Hence, another alterna-
CuBr(PPh3)3 with just 0.3–0.4 mol-% loading, the ligation tive strategy based on 1-(pyridin-2-yl)prop-2-yn-1-yl acetate
of 2-picolyl azide (1C) with phenylacetylenes 2(f–j,l–n) was (2cЈ) was tested. This compound was conveniently prepared
complete within 15 min, and the products [i.e., 5C(f–j,l–n)] following the report of Gevorgyan et al., as shown in
were isolated in 73–88% yield after crystallization from the Scheme 3. The addition of ethynylmagnesium bromide to
appropriate solvent, as indicated in the Exp. Sect. and picolinaldehyde gave a highly unstable propargyl alcohol
Table 3, entries 1–8. Care should be taken because these re- derivative, which was stabilized by in situ acetylation with
actions are fast and highly exothermic. If they are con- acetic anhydride in the presence of 4-dimethylaminopyr-
ducted at room temperature, the heat that is almost in- idine to give acetate 2cЈ.[27,28]
stantly released can cause an explosion-like evaporation of
the acetylene and azide reagents from the reaction mixture,
which is also accompanied by partial decomposition. On a
mmol scale, mixing the reagents and precatalyst at 0–10 °C
and then removing the cooling bath proved to be safe in
this respect.
Scheme 3. Synthesis of 2cЈ.[a] Yield of the pure product over two
steps from picolinaldehyde.
Table 3. Synthesis of 4-aryl-1-(heteroarylmethyl)-1,2,3-triazoles 5.
As described above for the preparation of library mem-
bers 5, the acetylene group in 2cЈ was ligated with selected
aryl azides 1F, 1H, and 1J by using CuBr(PPh3)3 (0.3 mol-
%) as precatalyst under solvent-free conditions to give acet-
oxy derivatives 6FcЈ, 6HcЈ, and 6JcЈ (Table 4). No cycloiso-
meration of acetate 2cЈ into the indolizine, which has pre-
viously been reported to proceed by copper catalysis,[29] was
observed in this step. In the last step of this reaction se-
quence, the acetoxy protecting group was removed by
hydrogenolysis (H2, Pd/C) to give 6Fc, 6Hc, and 6Jc. A
modified literature procedure, previously used for the re-
duction of the analogous benzyl alcohol derivatives, was ap-
plied.[30] The results are collected in Table 4.
Entry
Azide Alkyne
R
Cat. [mol- Product Yield [%]
[a]
1
2
%]
5
1
2
3
4
5
6
7
8
1C
1C
1C
1C
1C
1C
1C
1C
1D
1D
1D
1D
1E
1E
1E
1E
2f
2g
2h
2i
2j
2l
2m
2n
2f
2h
2m
2n
2f
2h
2m
2n
H
Me
OMe
CN
CF3
Cl
NO2
NMe2
H
OMe
NO2
NMe2
H
OMe
NO2
NMe2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.1
0.1
0.1
0.1
5Cf
5Cg
5Ch
5Ci
5Cj
5Cl
5Cm
5Cn
5Df
5Dh
5Dm
5Dn
5Ef
5Eh
5Em
5En
80
76
78
88
80
80
73
78
60
68
52
73
78
68
56
75
9
10
11
12
13
14
15
16
Table 4. Synthesis of 1-aryl-4-(2-picolyl)-1,2,3-triazoles 6.
[a] Yield of isolated pure product.
Using the same reaction conditions as for 2-picolyl azide
(1C), the CuAAC ligation of 2-(azidomethyl)pyrazine (1D)
and 4-(azidomethyl)pyrimidine (1E) with selected phenyl
acetylenes 2 and CuBr(PPh3)3 in 0.1–0.4 mol-% loading
conveniently gave the corresponding pyrazine- (Table 3, en-
tries 9–12) and pyrimidine- (Table 3, entries 13–16) ap-
pended triazoles 5.
2-Propargylpyridine (2c), which would be useful for the
preparation of isomeric 1-aryl-4-(2-picolyl)-1,2,3-triazoles 6
(Figure 1), could not be accessed through the reaction of
propargylmagnesium bromide with 2-bromopyridine, nor
Entry
Azide
1
R
H
Product
6Ј
Yield
[%][a]
Product Yield [%]
[a]
6
1
2
3
1F
1H
1J
6FcЈ
73
83
68
6Fc
6Hc
6Jc
78
91
90
OMe 6HcЈ
CF3 6JcЈ
by the reaction of 2-pyridylmagnesium bromide with prop- [a] Yield of isolated pure product.
4
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1,2,3-Triazoles Tethered to Heterocycles
NMR Spectroscopy
NO2 groups resonate at δ = 48–49 and 370–371 ppm,
respectively, consistent with literature data.[33]
A potential application of the heteroaryl triazoles under
investigation could be as ligands or ligand precursors for
metal coordination. In coordination chemistry with nitro-
gen-donor ligands, 15N NMR spectroscopy has been used
as a probe to assign the coordination in solution.[31–33] The
nitrogen atom in such ligands is exposed to the most dra-
matic changes upon coordination, but also the nitrogen
chemical shifts are highly sensitive to structural changes,
more so than 13C chemical shifts.[34] Although the low natu-
ral abundance of 15N and its low gyromagnetic ratio make
direct observation of the 15N nuclide difficult, this has been
largely circumvented by the advent of the inverse-detected
1
Table 5. Selected H, 13C, and 15N NMR chemical shifts[a] in ppm
for the compounds 3–6.
Entry
3
R
δH-5 δC-5
δN-1
δN-2
δN-3
δN-1Ј
1
2
3
4
5
6
7
8
9
3Af[b]
3Ag[c]
3Ah[b]
3Ai[c]
3Aj[c]
3Ak[c]
H
Me
9.39 118.2 261
8.78 116.4 260
358
357
358
359
359
358
360
357
364
365
363
353
352
353
353
353
352
355
352
285
283
286
284
283
283
286
285
OMe 9.27 117.2 262
CN 8.94 118.0 262
CF3 8.91 117.8 261
Br
8.82 116.9 261
3Am[b] NO2 9.69 120.5 264
3An[b]
3Bf[b]
NMe2 9.13 116.1 261
9.43 119.8 262
H
356 269[d]
357 269[d]
long-range heteronuclear shift correlation techniques, intro- 10
3Bm[b] NO2 9.73 122.2 263
11
12
13
14
15
16
17
18
19
20
3Bn[b]
4Fa[c],[e]
4Ga[c]
4Ha[c]
4Ia[c]
NMe2 9.16 117.6 261
H
Me
OMe 8.52 120.1 255
CN 8.68 119.6 253
CF3 8.68 119.7 254
Br
H
356 269[d]
duced by Bax and Summers.[32,35,36]
[f]
[f]
8.61 120.0 256
8.57 120.0 256
–
–
302
302
302
For the assignments of the proton and carbon reso-
nances in compounds 3–6, we carried out 1D NMR (1H
and 13C) and gradient-selected 2D NMR experiments (1H–
1H gs-COSY, 1H–13C gs-HSQC, 1H–13C gs-HMBC). To de-
termine the 15N chemical shifts, we used 1H–15N gs-HMBC
experiments, adjusting the parameters for a long-range 1H–
360
360
348
349
353
352
350
348
346
347
348
347
346
349
345
[f]
[f]
–
–
–
–
4Ja[c]
[f]
[f]
4Ka[c]
5Cf[b],[e]
5Cg[c]
5Ch[b]
5Ci[c]
8.59 119.7 254
8.67 122.7 247
7.89 119.8 247
360
364
363
364
365
365
364
367
363
364
363
366
363
365
364
367
363
360
302
313
313
313
311
311
311
313
313
Me
1
15N coupling constant of 5 Hz. A typical H–15N HMBC
OMe 8.55 121.3 247
CN 8.09 121.4 247
CF3 8.05 121.0 246
connectivity pattern for assigning the triazole 15N reso- 21
22
23
24
5Cj[c]
nances is illustrated in Figure 3 by curved arrows. The
atom-numbering scheme and selected data are presented in
Figure 3 and Table 5. The nitrogen atoms of the NMe2 and
5Cl[c]
Cl
7.94 120.2 246
5Cm[b] NO2 8.95 124.4 250
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
5Cn[b]
5Df[b]
5Dh[b]
NMe2 8.55 120.4 246
8.69 122.4 246
OMe 8.56 121.4 245
H
348 330[g]
346 331[g]
350 330[g]
346 331[g]
349 291[d]
348 291[d]
350 291[d]
347 291[d]
5Dm[b] NO2 8.96 124.6 248
5Dn[b]
5Ef[b]
5Eh[b]
NMe2 8.45 120.4 245
8.70 122.8 244
OMe 8.58 121.8 243
H
5Em[b] NO2 8.96 124.9 246
5En[b]
NMe2 8.46 120.8 242
8.11 121.7 255
6FcЈ[c]
H
352
351
355
352
351
307
307
307
310
310
311
6HcЈ[c] OMe 8.02 121.8 254
–
[f]
6JcЈ[c]
6Fc[c]
6Hc[c]
6Jc[c]
CF3 8.20 121.5 252
7.89 120.1 254
361
[f]
H
–
OMe 7.79 120.3 254
CF3 7.96 121.0 251
358
[f]
[f]
–
–
[a] Referenced to Si(CH3)4 [δ (13C) = 0 ppm, δ (1H) = 0 ppm] and
liquid ammonia [δ (15N) = 0 ppm]. [b] In CDCl3. [c] In [D6]DMSO.
[d] Assignable to N-1Ј and N-3Ј. [e] 13C NMR chemical shifts are
taken from the literature; see the Exp. Sect. [f] Not determined.
[g] Assignable to N-1Ј and N-4Ј.
1,2,3-Triazole Ring
The order of shielding in the 1,2,3-triazoles is N-1ϾϾ
N-3Ͼ N-2, which is consistent with literature reports.[12,37]
In compound series 3, the 15N NMR chemical shifts are in
the range δ = 260–264, 357–365, and 352–357 ppm for N-
1, N-2, and N-3, respectively (Table 5, entries 1–11). The
electronic nature of the aryl substituent R has an impact
on all the triazole nitrogen atoms. For example, in contrast
to 3Am (δN-1 = 264 ppm, Table 5, entry 7), which is func-
tionalized with an electron-withdrawing 4-(p-nitrophenyl)
group, thus deshielding the N-1 nitrogen atom, the electron-
releasing 4-(dimethylamino)phenyl substituent in 3An (δN-1
Figure 3. The atom-numbering scheme for compounds 3–6 (1,2,3-
triazole ring: simple figures; pyridine, pyrazine, and pyrimidine rings:
primed figures; benzene ring: double-primed figures. C-1ЈЈ is at-
tached to the 1,2,3-triazole ring), and curved arrows showing typical
1H–15N HMBC correlations to the triazole nitrogen atoms that were
in combination used for the assignments.
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= 261 ppm, Table 5, entry 8) results in a shielding effect. (Table 5, entries 37–39) the pyridine nitrogen atoms reso-
Replacing the 1-(2-pyridyl) group with a 1-(2-pyrimidyl) nate at δ = 311–313, 307, and 310–311 ppm, respectively.
group in compounds 3 causes a significant downfield shift- These values are in good agreement with literature reports
ing of the triazole N-1 and N-2 nitrogen atoms, whereas N- for 2-methylpyridine (δ = 309 ppm)[32,40] or 2-benzylpyr-
3 remains unaffected (compare Table 5, entries 1, 7, and 8 idine (δ = 316 ppm),[32,34,40] for example. In a π-conjugated
with entries 9, 10, and 11, respectively). This is a result of framework where the triazole N-1 atom is attached directly
the more efficient electron-withdrawing properties of the π- to the pyridine C-2Ј atom, i.e., in the 1-(2-pyridyl)triazole
deficient 2-pyrimidine ring compared with the pyridine series 3 (δ = 283–286 ppm, Table 5, entries 1–8), a large
ring, which effectively makes the triazole ring more elec- shielding effect of ca. 25 ppm can be observed. This is inter-
tron-deficient.
preted as being due to a response by the pyridine ring to
Due to the lack of some 1H–15N HMBC correlations, the π-donation of the triazole N-1 nitrogen atom, and to a
not all of the triazole 15N NMR chemical shifts could be lesser extent to the weakly π-excessive nature[41] of the tri-
determined for some library members 4. For those com- azole ring. The effect of the latter is seen in the 4-(2-pyridyl)
pounds where the chemical shifts could be measured, N-1, triazole series 4 (δ = 302 ppm, Table 5, entries 12–17), where
N-2, and N-3 were determined to resonate at δ = 253–256, the triazole C-4 atom is bound to the pyridine C-2Ј atom,
360, and 348–353 ppm, respectively (Table 5, entries 12–17). resulting in an intermediate shielding effect of ca. 8 ppm.
Unexpectedly, in contrast to compounds 3, the triazole N-
The pyrimidine nitrogen chemical shifts in the (4-pyr-
1 and N-3 atoms in compounds 4 are more shielded than imidyl)methylenetriazole series 5 (δ = 291 ppm, Table 5, en-
N-2 (compare Table 5, entries 2, 3, and 6 with entries 13, tries 30–33) are in agreement with literature data for 4-alk-
14, and 17, respectively). The electronic nature of the aryl ylpyrimidines (δ ≈ 291 ppm).[34,40] Unfortunately, the ap-
1
substituent R appears to have a marginal effect on the plied resolution of the H–15N gs-HMBC spectra (20 Hz)
chemical shifts of the triazole nitrogen atoms.
did not allow the separation of cross-peaks corresponding
In compound series 5, the 15N NMR chemical shifts to the two nitrogen atoms N-1Ј and N-3Ј. Similarly to what
span between δ = 242–250, 363–367, and 345–350 ppm for was described above, in the π-conjugated framework of (2-
the triazole N-1, N-2, and N-3, respectively (Table 5, en- pyrimidyl)triazole series 3 (δ = 269 ppm, Table 5, entries 9–
tries 18–33). Although the chemical shifts of N-2 and N-3 11), the pyrimidine nitrogen atoms are significantly shielded
lie roughly within the same range as those for the com- as their shifts move to high field by 22 ppm.
pounds 3 and 4, the chemical shifts of the N-1 nitrogen
The pyrazine nitrogen atoms in (4-pyrazinyl)methyl-
atom appear significantly upfield. The increased shielding enetriazole series 5 (Table 5, entries 26–29) resonate at δ =
of N-1 is rationalized by the absence conjugation with π- 330–331 ppm, which is consistent with literature data[39] for
deficient heterocycle,[38] which in 5 is attached to the tri- 2-methylpyrazine (δ = 331 and 333 ppm). As for the pyrim-
azole moiety through a methylene bridge. The electronic na- idine derivatives mentioned above, the chemical shifts for
ture of the R group has a similar effect on the chemical the nitrogen atoms N-1Ј and N-4Ј could not be separated.
shifts of all three triazole nitrogen atoms. For example, in
compound 5Cm (R = NO2, Table 5, entry 24), the δN-1
Based on the solubility considerations, the spectra of
compounds 3–6 were measured in CDCl3 or [D6]DMSO.
,
δN-2, and δN-3 resonances appear at δ = 250, 367, and As may be seen from Table 5, the choice of NMR solvent
349 ppm, whereas in 5Cn (R = NMe2, Table 5, entry 25) appears to have no significant effect on the 15N chemical
they can be found upfield at δ = 246, 363, and 345 ppm, shifts.[31]
respectively. As expected, replacement of the pyridine ring
NMR chemical shifts for the triazole H-5 and C-5 atoms
by pyrazine or pyrimidine has no effect on the 15N NMR of heteroaryl-triazoles 3–6 are collected in Table 5. For the
spectra (compare Table 5, entries 18–25, 26–29, and 30–33). complete set of resonances, see the Exp. Sect.
The 15N NMR chemical shifts of the triazole rings in the
compounds 6 and 6Ј appear in the range δ = 251–255, 358–
361, and 351–355 ppm for N-1, N-2, and N-3, respectively
Conclusions
(Table 5, entries 34–39). The influence of the electronic
properties of the R substituent on the 15N chemical shifts
is small.
A library of pyridine-, pyrazine-, and pyrimidine-func-
tionalized 1,4-disubstituted 1,2,3-triazoles was conveniently
created through the copper-catalysed cycloaddition between
organic azides and terminal alkynes. Three different cop-
per(I) sources were examined, including a CuSO4/sodium
Pyridine, Pyrimidine, and Pyrazine Rings
The 15N NMR chemical shifts of the pyridine, pyrimid- ascorbate couple, CuBr(PPh3)3, and (CuOTf)2·C6H6. The
ine, and pyrazine nitrogen atoms were also extracted from CuSO4/sodium ascorbate system worked well in aqueous
the 1H–15N gs-HMBC spectra, and are collected in Table 5. alcohol media, and was suitable for the cycloaddition reac-
The data are in good agreement with those for pyridine,[34] tions with aryl and alkyl (benzyl) azide partners. This sys-
pyrimidine,[34] and pyrazine[39] derivatives reported in the tem, however, was not amenable for the reactions of het-
literature.
eroaryl azides that have the azido group in the vicinity of
In more detail, in the 1-(2-picolyl)triazole series 5 the heteroaromatic nitrogen atom, such as 2-azidopyridine
(Table 5, entries 18–25), 6Ј (Table 5, entries 34–36), and 6 and 2-azidopyrimidine. These compounds undergo azide–
6
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1,2,3-Triazoles Tethered to Heterocycles
solid sample support. Melting points were determined with a
Kofler micro hot stage instrument. Reactions were monitored by
TLC on TLC-CARD silica gel, 220–440 mesh.
tetrazole equilibrium, with the tetrazolyl form as the pre-
vailing isomer, retarding the cycloaddition with the alkynes.
As the proportion of the azido isomer increases with
decreasing solvent dielectric constant and increasing tem- Caution: The handling of NaN3 and its products is dangerous be-
cause of their explosive character, along with the high toxicity of
any HN3 that could potentially be produced as a side-product.
Neat azides must not be heated or distilled, and all reactions should
be carried out on a small scale.
perature, the cycloaddition reactions with 2-azidopyridine
and 2-azidopyrimidine partners were carried out in boiling
toluene using (CuOTf)2·C6H6 or CuBr(PPh3)3 as copper(I)
sources. The latter proved to be superior due to its stability
to the oxygen in air and its high catalytic activity. In ad-
dition, copper-catalysed cycloadditions with CuBr(PPh3)3
under solvent-free conditions are discussed. As the com-
pounds under investigation will potentially serve as ligands
or ligand precursors for mono- and bidentate nitrogen or
N-heterocyclic carbene coordination to metal ions, we mea-
sured 1H, 13C, and 15N NMR spectra, and assigned the cor-
responding resonances. 15N NMR chemical shifts were con-
veniently determined at the natural abundance level of the
15N isotope using the 1H–15N gs-HMBC technique, and
were discussed in more detail. It is noteworthy that NMR
spectroscopy, and in particular 15N NMR spectroscopy, is
frequently a decisive technique for assigning the coordina-
tion mode of such ligands in solution.
4-(Azidomethyl)pyrimidine (1E): Brown-red oil. Rf (light petroleum/
ethyl acetate, 1:1) = 0.3. IR: ν = 2100, 1581, 1553, 1387, 1343, 1277,
˜
741 cm–1. 1H NMR (500 MHz, CDCl3): δ = 4.53 (s, 2 H, CH2),
7.41 (d, J = 5.1 Hz, 1 H, ArH), 8.78 (d, J = 5.1 Hz, 1 H, ArH),
9.20 (s, 1 H, ArH) ppm. 13C NMR (126 MHz, CDCl3): δ = 54.5
(CH2), 118.8, 157.9, 158.8, 164.4 (all aryl) ppm. HRMS (ESI+):
calcd. for C5H6N5 [M + H]+ 136.0618; found 136.0619.
+
Phenyl Azide (1F). General Procedure for the Synthesis of 1(F–K):
Aniline (1.86 g, 20.0 mmol) was dissolved in HCl (6 m aq.;
12.6 mL), and the solution was cooled (ca. 0 °C). An aqueous solu-
tion of sodium nitrite [1.40 g, 20.3 mmol in H2O (7 mL)] was slowly
added. The reaction temperature was not allowed to rise above
5 °C. In the same way, an aqueous solution of NaN3 [1.31 g,
20.1 mmol in H2O (7 mL)] was added, and stirring was continued
for 15 min at room temperature. The reaction mixture was neutral-
ized with saturated aqueous NaHCO3, and the product was ex-
tracted with diethyl ether (6ϫ 50 mL). The combined organic lay-
ers were dried with Na2SO4, filtered, and concentrated in vacuo.
The residue was purified by flash column chromatography on silica
gel (light petroleum/ethyl acetate, 5:2) to give phenyl azide (1F;
1.85 g, 15.5 mmol, 78%) as a yellow oil.
Experimental Section
General Methods: Reagents and solvents were used as obtained
from commercial sources (Sigma–Aldrich, Fluka, Alfa Aesar).
Tetrazolo[1,5-a]pyridine (1A),[13] tetrazolo[1,5-a]pyrimidine (1B),[21]
2-picolyl azide (1C),[23] 1-(pyridin-2-yl)prop-2-ynyl acetate (2cЈ),[27]
and CuBr(PPh3)3[25] were prepared by known procedures. 2-(Azido-
methyl)pyrazine (1D) was prepared from 2-methylpyrazine accord-
ing to the literature report.[42] The same procedure was used for the
preparation of 4-(azidomethyl)pyrimidine (1E); spectral and ana-
lytical data are given below.
The spectral data of phenyl azide (1F),[43] 4-methylphenyl azide
(1G),[43] 4-methoxyphenyl azide (1H),[43] 4-azidobenzonitrile
(1I),[44] 4-(trifluoromethyl)phenyl azide (1J),[45] and 4-bromophenyl
azide (1K)[46] were consistent with literature data.
General Procedure for the Synthesis of Triazoles 3: A mixture of
tetrazolo[1,5-a]pyridine (1A) or tetrazolo[1,5-a]pyrimidine (1B), the
appropriate phenyl acetylene 2(f–k,m,n), and CuBr(PPh3)3 was
heated in toluene at reflux, without the exclusion of air, for the
time indicated (Table 1). For the preparation of triazoles 3Ah, 3An,
and 3Bn, (CuOTf)2·C6H6 was used as precatalyst instead, and in
these cases, the reaction was carried out under an argon atmo-
sphere.
NMR spectra were measured with Bruker Avance 300 and Bruker
Avance III 500 spectrometers. Proton and carbon spectra were ref-
erenced to Si(CH3)4 as the internal standard. Some 13C chemical
shifts were determined relative to the 13C signal of the solvent:
CDCl3 (δ = 77.0 ppm), [D6]DMSO (δ = 39.5 ppm). 19F NMR spec-
tra were referenced to CCl3F as external standard at δ = 0 ppm.
15N chemical shifts were extracted from 1H–15N HMBC spectra
with a 20 Hz digital resolution in the indirect dimension. 15N chem-
ical shifts are reported to the nearest whole number as measured
from the spectrum. However, the data should not be considered to
be more accurate than Ϯ0.5 ppm because of the digital resolution
limits of the experiment. The reported 15N chemical shifts were
measured with respect to external 90% CH3NO2 in CDCl3, and
were converted to the δ [15N (liq. NH3)] = 0 ppm scale using the
To isolate 3Am and 3Bm, the reaction solvent was azeotropically
removed with the help of ethanol, and the crude product was
recrystallized from pyridine. To isolate other triazoles 3, the reac-
tion solvent was evaporated, and the residue was subjected to col-
umn chromatography on silica gel using a mixture of CH2Cl2 and
MeOH (50:1) as eluent. For analysis, the crude products were
recrystallized from the solvent indicated below. The quantities used
in the above procedure, and spectral and analytical data are given
relationship: δ [15N (CH3NO2)] = δ [15N (liq. NH3)] + 380.5 ppm. below.
Chemical shifts are given on the δ scale (ppm). Coupling constants
2-[4-Phenyl-1H-1,2,3-triazol-1-yl]pyridine (3Af,
R = H): Tet-
(J) are given in Hertz. Multiplicities are indicated as follows: s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br
(broadened).
razolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), ethynylbenzene
(2f; 102.1 mg, 1.00 mmol), toluene (20 mL), CuBr(PPh3)3 (37.2 mg,
0.04 mmol). Reaction time: 8 h. White solid (138 mg, 62%). Rf
1
An Agilent 6224 time-of-flight (TOF) mass spectrometer equipped
with a double orthogonal electrospray atmospheric pressure ioniza-
tion source (ESI) coupled to an Agilent 1260 HLPC instrument
was used for recording HRMS spectra. Elemental analysis was car-
ried out with a Perkin–Elmer 2400 Series II CHNS/O Analyser. IR
spectra were obtained with a Perkin–Elmer Spectrum 100 instru-
ment equipped with a Specac Golden Gate Diamond ATR as a
(CH2Cl2/MeOH, 50:1) = 0.6, m.p. 139–140 °C (tBuOH/water). H
NMR (500 MHz, [D6]DMSO): δ = 7.44–7.33 (m, 1 H, 4ЈЈ-H), 7.51
(dd, J = 10.5, 4.8 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.59 (ddd, J = 7.0, 4.9,
1.4 Hz, 1 H, 5Ј-H), 8.06 (dd, J = 5.1, 3.3 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H),
8.25–8.12 (m, 2 H, 3Ј-H, 4Ј-H), 8.65 (ddd, J = 4.8, 1.6, 0.9 Hz, 1 H,
6Ј-H), 9.39 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ
= 113.8 (C-3Ј), 118.2 (C-5), 124.3 (C-5Ј), 125.5 (C-3ЈЈ, C-5ЈЈ),
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7

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/KAP1
Date: 29-10-14 15:52:45
Pages: 16
A. Bolje, D. Urankar, J. Kosˇmrlj
FULL PAPER
128.35 (C-4ЈЈ), 128.9 (C-2ЈЈ, C-6ЈЈ), 130.0 (C-1ЈЈ), 140.1 (C-4Ј), 2-{4-[4-(Trifluoromethyl)phenyl]-1H-1,2,3-triazol-1-yl}pyridine (3Aj,
147.2 (C-4), 148.5 (C-2Ј), 148.9 (C-6Ј) ppm. 15N NMR (51 MHz,
[D6]DMSO): δ = 261 (N-1), 285 (N-1Ј), 353 (N-3), 358 (N-2) ppm.
The spectroscopic data are in agreement with those from the litera-
ture.[16]
R = CF3): Tetrazolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), 4-
ethynyl-α,α,α-trifluorotoluene (2j; 170.1 mg, 1.00 mmol), toluene
(20 mL), CuBr(PPh3)3 (37.2 mg, 0.04 mmol). Reaction time: 23 h.
Yellow solid (227.0 mg, 79%). Rf (CH2Cl2/MeOH, 50:1) = 0.6, m.p.
177–178 °C (tBuOH/water). IR: ν = 3138, 1807, 1615, 1594, 1474,
˜
2-[4-(p-Tolyl-1H-1,2,3-triazol-1-yl)]pyridine (3Ag, R = Me): Tet-
razolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), 4-ethynyl toluene
(2g; 116.0 mg, 1.00 mmol), toluene (20 mL), CuBr(PPh3)3 (37.2 mg,
0.04 mmol). Reaction time: 7 h. Pale brown solid (127.0 mg, 55%).
Rf (CH2Cl2/MeOH, 50:1) = 0.6, m.p. 119–122 °C (tBuOH/water);
1
1405, 1189, 1162, 1103, 8846, 825, 774 cm–1. H NMR (500 MHz,
CDCl3): δ = 7.40 (ddd, J = 7.4, 4.9, 1.1 Hz, 1 H, 5Ј-H), 7.73 (d, J
= 8.1 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.95 (ddd, J = 8.3, 7.4, 1.8 Hz, 1 H,
4Ј-H), 8.07 (d, J = 8.0 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.27 (d, J = 8.2 Hz
1 H, 3Ј-H), 8.55 (ddd, J = 4.9, 1.9, 0.9 Hz, 1 H, 6Ј-H), 8.91 (s, 1
H, 5-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 113.9 (C-3Ј),
117.8 (C-5), 125.2 (C-5Ј), 125.9 (q, J = 4 Hz, C-3ЈЈ, C-5ЈЈ), 126.0
(C-2ЈЈ, C-6ЈЈ), 126.2 (q, J = 272 Hz, CF3), 130.3 (q, J = 32 Hz, C-
4ЈЈ), 133.7 (C-1ЈЈ), 139.3 (C-4ЈЈ), 146.7 (C-4), 148.7 (C-6Ј), 149.0
(C-2Ј) ppm. 19F NMR (471 MHz, CDCl3): δ = –62.6 (s, 3 F, CF3)
ppm. 15N NMR (51 MHz, CDCl3): δ = 261 (N-1), 283 (N-1Ј), 353
lit. m.p. 119–122 °C[17]. IR: ν = 3150, 1593, 1577, 1472, 1460, 1402,
˜
1226, 1004, 988, 827, 806, 771, 723 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 2.41 (s, 3 H, CH3), 7.28 (d, J = 7.9 Hz, 2 H, 3ЈЈ-H,
5ЈЈ-H), 7.36 (ddd, J = 7.3, 4.9, 1.1 Hz, 1 H, 5Ј-H), 7.84 (d, J =
8.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 7.94 (ddd, J = 8.4, 7.6, 1.8 Hz, 1 H, 4Ј-
H), 8.26 (d, J = 8.2 Hz 1 H, 3Ј-H), 8.53 (dd, J = 5.6, 1.6 Hz, 1 H,
6Ј-H), 8.78 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz, CDCl3): δ =
21.4 (CH3), 113.9 (C-3Ј), 116.4 (C-5), 123.5 (C-5Ј), 125.8 (C-2ЈЈ, C-
6ЈЈ), 127.4 (C-1ЈЈ), 129.6 (C-3ЈЈ, C-5ЈЈ), 138.4 (C-4ЈЈ), 139.1 (C-4Ј),
148.1 (C-4), 148.5 (C-6Ј), 149.2 (C-2Ј) ppm. 15N NMR (51 MHz,
(N-3), 359 (N-2) ppm. HRMS (ESI+): calcd. for C14H10F3N4
+
[M + H]+ 291.0852; found 291.0852. C14H9F3N4 (290.25): calcd. C
57.93, H 3.13, N 19.30; found C 57.69, H 3.06, N 19.06.
CDCl3): δ = 260 (N-1), 283 (N-1Ј), 352 (N-3), 357 (N-2) ppm. 2-[4-(4-Bromophenyl)-1H-1,2,3-triazol-1-yl]pyridine (3Ak, R = Br):
+
HRMS (ESI+): calcd. for C14H13N4 [M + H]+ 237.1135; found
237.1134. C14H12N4·0.1H2 O: calcd. C 70.63, H 5.17, N 23.53;
found C 70.81, H 4.87, N 23.23.
Tetrazolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), 1-bromo-4-
ethynylbenzene (2k; 181.0 mg, 1.00 mmol), toluene (20 mL),
CuBr(PPh3)3 (37.2 mg, 0.04 mmol). Reaction time: 8 h. Brown so-
lid (223.0 mg, 74%). Rf (CH2Cl2/MeOH, 50:1) = 0.6, m.p. 181–
2-[4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]pyridine (3Ah,
R =
182 °C (tBuOH/water); lit. m.p. 174–176 °C[17]. IR: ν = 3134, 1897,
˜
OMe): Tetrazolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), 4-eth-
ynylanisole (2h; 132.1 mg, 1.00 mmol), toluene (20 mL), (CuOTf)
2·C6H6 (22.6 mg, 0.05 mmol). Reaction time: 25 h. White solid
(475.0 mg, 62%). Rf (CH2Cl2/MeOH, 50:1) = 0.6, m.p. 73–74 °C
1
1575, 1457, 1392, 1229, 1145, 1066, 1002, 814, 771 cm–1. H NMR
(500 MHz, CDCl3): δ = 7.38 (ddd, J = 7.4, 4.9, 1.0 Hz, 1 H, 5Ј-H),
7.60 (d, J = 8.5 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.82 (d, J = 8.5 Hz, 2 H,
2ЈЈ-H, 6ЈЈ-H), 7.95 (ddd, J = 8.3, 7.4, 1.8 Hz, 1 H, 4Ј-H), 8.25 (d,
J = 8.2 Hz, 1 H, 3Ј-H), 8.53 (ddd, J = 4.9, 1.9, 0.9 Hz, 1 H, 6Ј-H),
8.82 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 113.9
(C-3Ј), 116.9 (C-5), 122.4 (C-4ЈЈ), 123.7 (C-5Ј), 127.4 (C-2ЈЈ, C-6ЈЈ),
129.2 (C-1ЈЈ), 132.1 (C-3ЈЈ, C-5ЈЈ), 139.2 (C-4Ј), 147.0 (C-4), 148.6
(C-6Ј), 149.1 (C-2Ј) ppm. 15N NMR (51 MHz, CDCl3): δ = 261
(N-1), 283 (N-1Ј), 352 (N-3), 358 (N-2) ppm. HRMS (ESI+): calcd.
(ethyl acetate/n-hexane); lit. m.p. 106–109 °C[17]. IR: ν = 3161,
˜
3109, 3059, 3015, 2941, 2833, 1616, 1577, 1561, 1502, 1463, 1283,
1226, 1180, 1023, 1003, 831, 797, 775, 724 cm–1. 1H NMR
(500 MHz, [D6]DMSO): δ = 3.82 (s, 3 H, OCH3), 7.06 (d, J =
8.8 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.57 (ddd, J = 6.7, 4.9, 1.5 Hz, 1 H, 5Ј-
H), 7.97 (d, J = 8.8 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.21–8.09 (m, 2 H, 3Ј-
H, 4Ј-H), 8.67–8.58 (m, 1 H, 6Ј-H), 9.27 (s, 1 H, 5-H) ppm. 13C
NMR (126 MHz, [D6]DMSO): δ = 55.2 (OCH3), 113.7 (C-3Ј),
114.4 (C-3ЈЈ, C-5ЈЈ), 117.2 (C-5), 122.5 (C-1ЈЈ), 124.2 (C-5Ј), 127.0
(C-2ЈЈ, C-6ЈЈ), 140.1 (C-4Ј), 147.2 (C-4), 148.6 (C-2Ј), 148.9 (C-6Ј),
for C13H10BrN4 [M + H]+ 301.0083; found 301.0081. C13H9BrN4
+
(301.14): calcd. C 51.85, H 3.01, N 18.60; found C 52.12, H 2.76,
N 18.35.
159.4 (C-4ЈЈ) ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 262 (N- 2-[4-(4-Nitrophenyl)-1H-1,2,3-triazol-1-yl]pyridine (3Am, R = NO2):
1), 286 (N-1Ј), 353 (N-3), 358 (N-2) ppm. HRMS (ESI+): calcd.
for C14H13N4O+ [M + H]+ 253.1084; found 253.1086. C14H12N4O
(252.28): calcd. C 66.65, H 4.79, N 22.21; found C 66.43, H 4.56,
N 22.082.
Tetrazolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), 4-ethynyl-
nitrobenzene (2m; 147.0 mg, 1.00 mmol), toluene (20 mL),
CuBr(PPh3)3 (37.2 mg, 0.04 mmol). Reaction time: 17 h. White so-
lid (193.1 mg, 71%). Rf (CH2Cl2/MeOH, 50:1) = 0.6, m.p. 266–
268 °C (pyridine). IR: ν = 3140, 3102, 3072, 1593, 1513, 1460, 1401,
˜
2-[4-(4-Cyanophenyl)-1H-1,2,3-triazol-1-yl]pyridine (3Ai, R = CN):
Tetrazolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), 4-ethynylben-
zonitrile (2i; 127.0 mg, 1.00 mmol), toluene (20 mL), CuBr(PPh3)3
(37.2 mg, 0.04 mmol). Reaction time: 16 h. White solid (127.0 mg,
52%). Rf (CH2Cl2/MeOH, 50:1) = 0.6, m.p. 241–243 °C (tBuOH/
1334, 1314, 1238, 1193, 1101, 1029, 1005, 853, 824, 780, 756, 708,
689 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 7.65–7.57 (m, 1
H, 5Ј-H), 8.19 (ddd, J = 10.4, 9.9, 4.9 Hz, 2 H, 3Ј-H, 4Ј-H), 8.42–
8.29 (m, 4 H, 2ЈЈ-H, 3ЈЈ-H, 5ЈЈ-H, 6ЈЈ-H), 8.71–8.61 (m, 1 H, 6Ј-
H), 9.69 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ
= 114.0 (C-3Ј), 120.5 (C-5), 124.4 (C-2ЈЈ, C-6ЈЈ or C-3ЈЈ, C-5ЈЈ),
124.7 (C-5Ј), 126.5 (C-3ЈЈ, C-5ЈЈ or C-2ЈЈ, C-6ЈЈ), 136.4 (C-1ЈЈ),
140.3 (C-4Ј), 145.3 (C-4), 147.0 (C-4ЈЈ), 148.3 (C-2Ј), 149.0 (C-6Ј)
ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 264 (N-1), 286 (N-1Ј),
355 (N-3), 360 (N-2), 371 (NO2) ppm. HRMS (ESI+): calcd. for
water). IR: ν = 3137, 2222, 1594, 1472, 1460, 1030, 1006, 816,
˜
777 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.42 (ddd, J = 7.4, 4.9,
1.0 Hz, 1 H, 5Ј-H), 7.78 (d, J = 8.8 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.99
(ddd, J = 8.2, 7.5, 1.9 Hz, 1 H, 4Ј-H), 8.09 (d, J = 8.7 Hz, 2 H, 2ЈЈ-
H, 6ЈЈ-H), 8.29 (d, J = 8.2 Hz 1 H, 3Ј-H), 8.57 (ddd, J = 4.9, 1.9,
0.9 Hz, 1 H, 6Ј-H), 8.94 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz,
CDCl3): δ = 111.8 (C-4ЈЈ), 113.9 (C-3Ј), 118.0 (C-5), 118.8 (CN),
124.0 (C-5Ј), 126.3 (C-2ЈЈ, C-6ЈЈ), 132.8 (C-3ЈЈ, C-5ЈЈ), 134.6 (C-
1ЈЈ), 139.4 (C-4Ј), 146.2 (C-4), 148.7 (C-6Ј), 149.0 (C-2Ј) ppm. 15N
NMR (51 MHz, CDCl3): δ = 262 (N-1), 284 (N-1Ј), 353 (N-3), 359
C13H10N5O2 [M + H]+ 268.0829; found 268.0821. C13H9N5O2
+
(267.25): calcd. C 58.43, H 3.39, N 26.21; found C 58.57, H 3.19,
N 26.06.
2-{4-[4-(Dimethylamino)phenyl]-1H-1,2,3-triazol-1-yl}pyridine (3An,
R = NMe2): Tetrazolo[1,5-a]pyridine (1A; 120.0 mg, 1.00 mmol), 4-
ethynyl-N,N-dimethylaniline (2m; 144.85 mg, 1.00 mmol), toluene
(20 mL), (CuOTf)2·C6H6 (12.0 mg, 0.02 mmol). Reaction time:
(N-2) ppm. HRMS (ESI+): calcd. for C14H10N5 [M + H]+
+
248.0931; found 248.0930. C14H9F3N4 (290.25): calcd. C 68.01, H
3.67, N 28.32; found C 68.37, H 3.40, N 28.18.
8
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O43100
/KAP1
Date: 29-10-14 15:52:45
Pages: 16
1,2,3-Triazoles Tethered to Heterocycles
17 h. Pale yellow solid (188.0 mg, 71%), m.p. 151.5–152 °C. IR: ν
(C-5Ј), 126.6 (C-2ЈЈ, C-6ЈЈ), 147.6 (C-4), 150.4 (C-4ЈЈ), 153.9 (C-2Ј),
159.8 (C-4Ј, C-6Ј) ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 49
˜
= 3156, 2894, 2808, 2104, 1615, 1594, 1574, 1508, 1458, 1354, 1223,
1200, 1023, 944, 820, 792, 772, 719 cm–1. 1H NMR (500 MHz, [D6]- [N(CH3)2], 261 (N-1), 269 (N-1Ј, N-3Ј), 356 (N-3), 363 (N-2) ppm.
+
DMSO): δ = 2.96 [s, 6 H, N(CH3)2], 6.81 (d, J = 8.9 Hz, 2 H, 3ЈЈ- HRMS (ESI+): calcd. for C14H15N6 [M + H]+ 267.1353; found
H, 5ЈЈ-H), 7.53–7.58 (m, 1 H, 5Ј-H), 7.84 (d, J = 8.9 Hz, 2 H, 2ЈЈ- 267.1353. C14H14N6 (266.30): calcd. C 63.14, H 5.30, N 31.56;
H, 6ЈЈ-H), 8.11–8.17 (m, 2 H, 3Ј-H, 4Ј-H), 8.61–8.64 (m, 1 H, 6Ј- found C 63.42, H 5.15, N 31.60.
H), 9.13 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ
General Procedure for the Synthesis of Triazoles 4: A mixture
= 39.5 [N(CH3)2], 112.3 (C-3ЈЈ, C-5ЈЈ), 113.6 (C-3Ј), 116.1 (C-5),
of the appropriate azidobenzene 1(F–K), 2-ethynylpyridine (2a),
117.6 (C-1ЈЈ), 124.1 (C-5Ј), 126.5 (C-2ЈЈ, C-6ЈЈ), 140.0 (C-4Ј), 147.9
CuSO4·5H2O, and sodium ascorbate in MeOH/H2O was stirred at
(C-4), 148.6 (C-6Ј), 148.9 (C-6Ј), 150.3 (C-4ЈЈ) ppm. 15N NMR
room temperature for 1 h. Saturated aqueous NH4Cl was added,
(51 MHz, [D6]DMSO): δ = 49 [N(CH3)2], 261 (N-1), 285 (N-1Ј),
and the product was extracted into CH2Cl2. The combined organic
352 (N-3), 357 (N-2) ppm. HRMS (ESI+): calcd. for C15H16N5
+
layers were washed with brine, and dried with anhydrous Na2SO4,
[M + H]+ 266.1400; found 266.1459. C15H15N5 (265.32): calcd. C
and the solvent was evaporated to give pure 4(F–K)a. The quanti-
ties used in the above procedure, spectral and analytical data are
67.90, H 5.70, N 26.40; found C 67.87, H 5.70, N 26.31.
given below.
2-[4-Phenyl-1H-1,2,3-triazol-1-yl]pyrimidine (3Bf, R = H): Tet-
razolo[1,5-a]pyrimidine (1B; 121.0 mg, 1.00 mmol), ethynylbenzene
(2f; 102.1 mg, 1.00 mmol), toluene (10 mL), CuBr(PPh3)3 (18.7 mg,
0.03 mmol). Reaction time: 7 h at reflux, 24 h at room temp. Pale
2-(1-Phenyl-1H-1,2,3-triazol-4-yl)pyridine (4Fa, R = H): Azido-
benzene (1F; 1.190 g, 10.0 mmol), 2-ethynylpyridine (2a; 1.030 g,
10.0 mmol), MeOH/H2O (120/80 mL), CuSO4·5H2O (124.0 mg,
0.5 mmol), sodium ascorbate (3.394 g, 20.0 mmol). NH4Cl
(200 mL), CH2Cl2 (4ϫ 200 mL), brine (200 mL). Pale brown solid
brown solid (128.1 mg, 58%), m.p. 139–140 °C. IR: ν = 3156, 3081,
˜
1576, 1563, 1463, 1428, 1391, 1355, 1229, 1027, 1013, 831, 811,
788, 766, 742, 691 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 7.41
(t, J = 7.4 Hz, 1 H, 4ЈЈ-H), 7.51 (t, J = 7.6 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H),
7.72 (t, J = 4.8 Hz, 1 H, 5Ј-H), 8.07 (d, J = 7.1 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-
H), 9.06 (d, J = 4.8 Hz, 2 H, 4Ј-H, 6Ј-H), 9.43 (s, 1 H, 5-H) ppm.
13C NMR (126 MHz, [D6]DMSO): δ = 119.8 (C-5), 121.7 (C-5Ј),
125.6 (C-2ЈЈ, C-6ЈЈ), 128.5 (C-4ЈЈ), 129.0 (C-3ЈЈ, C-5ЈЈ), 129.8 (C-
1ЈЈ), 146.9 (C-4), 153.8 (C-2ЈЈ), 159.8 (C-3Ј, C-6Ј) ppm. 15N NMR
(51 MHz, [D6]DMSO): δ = 262 (N-1), 269 (N-1Ј, N-3Ј), 356 (N-3),
(1.832 g, 83%). R (ethyl acetate) = 0.4, m.p. 89–92 °C. IR: ν =
˜
f
3118, 3051, 1592, 1567, 1544, 1502, 1464, 1252, 1236, 1186, 1146,
994, 970, 841, 792, 756, 722 cm–1. H NMR (500 MHz, CDCl3): δ
1
= 7.26–7.29 (m, 1 H), 7.46–7.58 (m, 3 H), 7.82–7.84 (m, 3 H), 8.26–
8.28 (d, 1 H), 8.61–8.64 (m, 2 H) ppm. 15N NMR (51 MHz,
CDCl3): δ = 256 (N-1), 302 (N-1Ј) ppm. The spectroscopic data
are in agreement with those from the literature.[47]
364 (N-2) ppm. HRMS (ESI+): calcd. for C12H10N5 [M + H]+
+
2-[1-(p-Tolyl)-1H-1,2,3-triazol-4-yl]pyridine (4Ga, R = Me): 4-
Azidotoluene (1G; 1.332 g, 10.0 mmol), 2-ethynylpyridine (2a;
1.030 g, 10.0 mmol), MeOH/H2O (120/80 mL), CuSO4·5H2O
(124.0 mg, 0.5 mmol), sodium ascorbate (3.394 g, 20 mmol).
NH4Cl (200 mL), CH2Cl2 (4ϫ 200 mL), brine (200 mL). Brown
solid (1.654 g, 70%). Rf (ethyl acetate) = 0.4, m.p. 180–181 °C. IR:
224.0931; found 224.0930. C12H9N5 (223.24): calcd. C 64.56, H
4.06, N 31.36; found C 64.20, H 3.74, N 30.96.
2-[4-(4-Nitrophenyl)-1H-1,2,3-triazol-1-yl]pyrimidine (3Bm,
R =
NO2): Tetrazolo[1,5-a]pyrimidine (1B; 121.0 mg, 1.00 mmol), 4-
ethynyl-nitrobenzene (2m; 147.0 mg, 1.00 mmol), toluene (10 mL),
CuBr(PPh3)3 (18.7 mg, 0.03 mmol). Reaction time: 17 h. Pale
ν = 3131, 3057, 2912, 1597, 1515, 1470, 1402, 1235, 1036, 988, 809,
˜
777, 736, 705 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.44 (3 H,
CH3), 7.27 (dd, J = 7.7, 4.7 Hz, 1 H, 5Ј-H), 7.35 (d, J = 8.2 Hz, 2
H, 3ЈЈ-H, 5ЈЈ-H), 7.69 (d, J = 8.4 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 7.82 (dt,
J = 7.7, 1.8 Hz, 1 H, 4Ј-H), 8.26 (d, J = 8.0 Hz, 1 H, 3Ј-H), 8.57
(s, 1 H, 5-H), 8.62 (d, J = 4.7 Hz, 1 H, 6Ј-H) ppm. 13C NMR
(126 MHz, CDCl3): δ = 21.2 (CH3), 120.0 (C-5), 120.4 (C-2ЈЈ, C-
6ЈЈ), 120.4 (C-3Ј), 123.1 (C-5Ј), 130.3 (C-3ЈЈ, C-5ЈЈ), 134.7 (C-1ЈЈ),
137.0 (C-4Ј), 139.0 (C-4ЈЈ), 148.8 (C-4), 149.5 (C-6Ј), 150.1 (C-2Ј)
ppm. 15N NMR (51 MHz, CDCl3): δ = 256 (N-1), 302 (N-1Ј), 348
brown solid (114.3 mg, 43%), m.p. 286–287 °C (pyridine). IR: ν =
˜
3162, 3138, 3107, 3060, 3015, 2941, 2833, 1601, 1575, 1503, 1460,
1434, 1393, 1333, 1280, 1236, 1181, 1105, 1018, 852, 828, 814, 789,
1
756, 709, 630 cm–1. H NMR (500 MHz, [D6]DMSO): δ = 7.75 (t,
J = 4.9 Hz, 1 H, 5Ј-H), 8.36 (br. s, 4 H, 2ЈЈ-H, 3ЈЈ-H, 5ЈЈ-H, 6ЈЈ-
H), 9.08 (d, J = 4.9 Hz, 2 H, 4Ј-H, 6Ј-H), 9.73 (s, 1 H, 5-H) ppm.
13C NMR (126 MHz, [D6]DMSO): δ = 122.0 (C-5Ј), 122.2 (C-5),
124.4 (C-2ЈЈ, C-6ЈЈ or C-3ЈЈ, C-5ЈЈ), 126.6 (C-3ЈЈ, C-5ЈЈ or C-2ЈЈ, C-
6ЈЈ), 136.2 (C-1ЈЈ), 145.1 (C-4), 147.0 (C-4ЈЈ), 153.7 (C-2ЈЈ), 159.9
(C-3Ј, C-6Ј) ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 263 (N-
1), 269 (N-1Ј, N-3Ј), 357 (N-3), 365 (N-2), 370 (NO2) ppm. HRMS
(ESI+): calcd. for C12H9N6O2+ [M + H]+ 269.0787; found 269.0786.
C12H8N6O2 (268.23): calcd. C 53.73, H 3.01, N 31.33; found C
53.84, H 2.81, N 31.09.
(N-3), 360 (N-2) ppm. HRMS (ESI+): calcd. for C14H13N4 [M +
+
H]+ 237.1135; found 237.1133. C14H12N4 (236.28): calcd. C 65.54,
H 4.23, N 23.52; found C 65.20, H 3.98, N 23.33. The spectroscopic
data are in agreement with those from the literature.[48]
2-[1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl]pyridine (4Ha, R =
OMe): 1-Azido-4-methoxybenzene (1H; 1.491 g, 10.0 mmol), 2-
N,N-Dimethyl-4-[1-(pyrimidin-2-yl)-1H-1,2,3-triazol-4-yl]aniline ethynylpyridine (2a; 1.03 g, 10.0 mmol), MeOH/H2O (120/80 mL),
(3Bn, R = NMe2): Tetrazolo[1,5-a]pyrimidine (1B; 121.0 mg, CuSO4·5H2O (124.0 mg, 0.5 mmol), sodium ascorbate (3.394 g,
1.00 mmol), 4-ethynyl-N,N-dimethylaniline (2n; 144.9 mg, 20.0 mmol). NH4Cl (200 mL), CH2Cl2 (4ϫ 200 mL), brine
1.00 mmol), toluene (10 mL), (CuOTf)2·C6H6 (12.0 mg, 0.02 mmol).
(200 mL). Brown solid (2.254 g, 90%). Rf (ethyl acetate) = 0.4, m.p.
124–126 °C. IR: ν = 3161, 3015, 2832, 1887, 1578, 1462, 1283, 1248,
Reaction time: 7 h at reflux, 48 h at room temp. Pale brown solid
˜
(152.3 mg, 57%), m.p. 217–218 °C (acetonitrile). IR: ν = 3162, 1199, 1046, 1023, 1003, 831, 798, 774, 724, 621 cm–1. 1H NMR
˜
3036, 2895, 2810, 1614, 1564, 1510, 1456, 1433, 1355, 1228, 1197,
(500 MHz, CDCl3): δ = 3.89 (s, 3 H, CH3O), 7.05 (d, J = 8.9 Hz,
2 H, 3ЈЈ-H, 5ЈЈ-H), 7.27 (m, 1 H, 5Ј-H), 7.72 (d, J = 9.0 Hz, 2 H,
2ЈЈ-H, 6ЈЈ-H), 7.82 (t, J = 7.7 Hz, 1 H, 4Ј-H), 8.26 (d, J = 7.5 Hz,
1
1015, 985, 944, 831, 806, 785, 739, 629 cm–1. H NMR (500 MHz,
[D6]DMSO): δ = 2.96 [s, 6 H, N(CH3)2], 6.81 (d, J = 8.9 Hz, 2 H,
3ЈЈ-H, 5ЈЈ-H), 7.68 (t, J = 4.9 Hz, 1 H, 5Ј-H), 7.86 (d, J = 8.9 Hz, 1 H, 3Ј-H), 8.52 (s, 1 H, 5-H), 8.63 (br. d, 1 H, 6Ј-H) ppm. 13C
2 H, 2ЈЈ-H, 6ЈЈ-H), 9.03 (d, J = 4.9 Hz, 2 H, 4Ј-H, 5Ј-H), 9.16 NMR (126 MHz, CDCl3): δ = 55.7 (CH3O), 114.9 (C-3ЈЈ, C-5ЈЈ),
(s, 1 H, 5-H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ = 39.5 120.1 (C-5), 120.4 (C-3Ј), 122.1 (C-2ЈЈ, C-6ЈЈ), 123.1 (C-5Ј), 130.5
[N(CH3)2], 112.3 (C-3ЈЈ, C-5ЈЈ), 117.4 (C-1ЈЈ), 117.6 (C-5), 121.4 (C-1ЈЈ), 137.0 (C-4Ј), 148.8 (C-4), 149.5 (C-6Ј), 150.1 (C-2Ј), 159.9
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O43100
/KAP1
Date: 29-10-14 15:52:45
Pages: 16
A. Bolje, D. Urankar, J. Kosˇmrlj
FULL PAPER
(C-4ЈЈ) ppm. 15N NMR (51 MHz, CDCl3): δ = 255 (N-1), 302 (N-
for C13H10BrN4 [M + H]+ 301.0083; found 301.0077. C13H9BrN4
(301.14): calcd. C 51.85, H 3.01, N 18.60; found C 51.60, H 2.80,
+
1Ј), 349 (N-3), 360 (N-2) ppm. HRMS (ESI+): calcd. for
C14H13N4O+ [M + H]+ 253.1084; found 253.1084. C14H12N4O N 18.50. The spectroscopic data are in agreement with those from
(252.28): calcd. C 66.45, H 4.79, N 22.21; found C 66.01, H 4.45,
N 21.99. The spectroscopic data are in agreement with those from
the literature.[49]
the literature.[8]
General Procedure for the Synthesis of Triazoles 5: A mixture of
azide 1C–1E and phenylacetylene 2(f–j,l–n) was cooled to ca. 10 °C
in an ice-water bath, and CuBr(PPh3)3 was added to the stirred
mixture. The reaction mixture was stirred at room temperature for
15 min (until TLC analysis indicated compete consumption of
starting material), during which time the reaction mixture darkened
and became solid. The pure products 5 were isolated by recrystalli-
zation of the crude reaction mixture from the appropriate solvent
indicated below. The quantities used in the above procedure, and
the spectral and analytical data are given below.
2-[1-(4-Cyanophenyl)-1H-1,2,3-triazol-4-yl]pyridine (4Ia, R = CN):
4-Azidobenzonitrile (1I; 1.441 g, 10.0 mmol), 2-ethynylpyridine
(2a; 1.03 g, 10.0 mmol), MeOH/H2O (120/80 mL), CuSO4·5H2O
(124.0 mg, 0.5 mmol), sodium ascorbate (3.394 g, 20.0 mmol).
NH4Cl (200 mL), CH2Cl2 (4ϫ 200 mL), brine (200 mL). Red-
brown solid (2.095 g, 85%). Rf (ethyl acetate) = 0.4, m.p. 224–
226 °C. IR: ν = 3124, 3078, 2228, 1600, 1509, 1233, 1031, 828, 781,
˜
741, 621 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.31 (ddd, J =
7.7, 4.6, 1.0 Hz, 1 H, 5Ј-H), 7.78 (dt, J = 7.8, 1.8 Hz, 1 H, 4Ј-H),
7.88 (d, J = 8.7 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 8.01 (d, J = 8.8 Hz, 2 H,
2ЈЈ-H, 6ЈЈ-H), 8.26 (d, J = 7.9 Hz, 1 H, 3Ј-H), 8.64 (dd, J = 4.7,
1.0 Hz, 1 H, 6Ј-H), 8.68 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz,
CDCl3): δ = 117.7 (CN), 119.6 (C-5), 120.5 (C-2ЈЈ, C-6ЈЈ), 120.6
(C-3Ј), 122.5 (C-4ЈЈ), 123.5 (C-5Ј), 134.0 (C-3ЈЈ, C-5ЈЈ), 137.1 (C-
4Ј), 139.8 (C-1ЈЈ), 149.3 (C-6Ј), 149.7 (C-4), 149.8 (C-2Ј) ppm. 15N
NMR (51 MHz, CDCl3): δ = 253 (N-1), 353 (N-3) ppm. HRMS
2-{[4-Phenyl-1H-1,2,3-triazol-1-yl]methyl}pyridine (5Cf, R = H): 2-
Picolyl azide (1C; 134.0 mg, 1.00 mmol), phenylacetylene (2f;
102.1 mg, 1.00 mmol), CuBr(PPh3)3 (3 mg, 0.003 mmol). The crude
product was recrystallized from ethyl acetate/light petroleum.
White solid (189.0 mg, 80%). Rf (light petroleum/ethyl acetate, 5:3)
= 0.2, m.p. 78.5–79 °C (ethyl acetate/light petroleum). 1H NMR
(500 MHz, [D6]DMSO): δ = 5.77 (s, 2 H, CH2), 7.31–7.39 (m, 3 H,
5Ј-H, 3Ј-H, 4ЈЈ-H), 7.42–7.47 (m, 2 H, 5ЈЈ-H, 3ЈЈ-H), 7.82–7.89 (m,
3 H, 4Ј-H, 2ЈЈ-H, 6ЈЈ-H), 8.55–8.57 (m, 1 H, 6Ј-H), 8.67 (s, 1 H, 5-
H) ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 247 (N-1), 313
(N-1Ј), 348 (N-3), 364 (N-2) ppm. The spectroscopic data are in
agreement with those from the literature.[6]
+
(ESI+): calcd. for C14H10N5 [M + H]+ 248.0931; found 248.0930.
C14H9N5 (247.26): calcd. C 68.01, H 3.67, N 28.32; found C 67.65,
H 3.46, N 28.17.
2-{1-[4-(Trifluoromethyl)phenyl]-1H-1,2,3-triazol-4-yl}pyridine (4Ja,
R
= CF3): 1-Azido-4-(trifluoromethyl)benzene (1J; 1.871 g,
2-{[4-(p-Tolyl)-1H-1,2,3-triazol-1-yl]methyl}pyridine (5Cg, R = Me):
2-Picolyl azide (1C; 134.0 mg, 1.00 mmol), 4-ethynyltoluene (2g;
116.0 mg, 1.00 mmol), CuBr(PPh3)3 (3.0 mg, 0.003 mmol). The
crude product was recrystallized from tBuOH/water. Pale brown
solid (188.6 mg, 76%). Rf (light petroleum/ethyl acetate, 5:3) = 0.2,
10.0 mmol), 2-ethynylpyridine (2a; 1.030 g, 10.0 mmol), MeOH/
H2O (120/80 mL), CuSO4·5H2O (124.0 mg, 0.5 mmol), sodium as-
corbate (3.394 g, 20.0 mmol). NH4Cl (200 mL), CH2Cl2 (4ϫ
200 mL), brine (200 mL). Brown solid (2.342 g, 81%). Rf (ethyl
acetate) = 0.4, m.p. 158–160 °C. IR: ν = 3119, 1614, 1408, 1322,
˜
m.p. 99.5–101 °C (tBuOH/water). IR: ν = 3145, 3052, 3016, 1588,
˜
1166, 1103, 1066, 1033, 1016, 845, 784, 722, 693 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 7.30 (dd, J = 7.7, 4.3 Hz, 1 H, 5Ј-H), 7.83–
7.85 (m, 3 H, 4Ј-H, 3ЈЈ-H, 5ЈЈ-H), 7.99 (d, J = 8.3 Hz, 2 H, 2ЈЈ-H,
6ЈЈ-H), 8.27 (d, J = 7.9 Hz, 1 H, 3Ј-H), 8.64 (d, J = 4.8 Hz, 1 H,
6Ј-H), 8.68 (s, 1 H, 5-H) ppm. 13C NMR (126 MHz, CDCl3): δ =
119.7 (C-5), 120.3 (C-2ЈЈ, C-6ЈЈ), 120.6 (C-3Ј), 123.4 (C-5Ј), 123.6
(q, J = 272 Hz, CF3), 127.3 (q, J = 4 Hz, C-3ЈЈ, C-5ЈЈ), 130.8 (q, J
= 33 Hz, C-4ЈЈ), 137.1 (C-4Ј), 139.4 (C-1ЈЈ), 149.5 (C-4), 149.5 (C-
2Ј), 149.6 (C-6Ј) ppm. 15N NMR (51 MHz, CDCl3): δ = 254 (N-
1), 352 (N-3) ppm. 19F NMR (471 MHz, CDCl3): δ = –62.6 (s, 3
1570, 1497, 1473, 1456, 1256, 1068, 995, 828, 793, 753, 717 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.37 (s, 3 H, CH3), 5.69 (s, 2 H,
CH2), 7.20–7.30 (m, 4 H, 3Ј-H, 3ЈЈ-H, 5ЈЈ-H, 5Ј-H), 7.68 (ddd, J =
7.7, 7.7, 1.8 Hz, 1 H, 4Ј-H), 7.72 (d, J = 8.2 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-
H), 7.89 (s, 1 H, 5-H), 8.61 (d, J = 3.3 Hz, 1 H, 6Ј-H) ppm. 13C
NMR (126 MHz, CDCl3): δ = 21.3 (CH3), 55.7 (CH2), 119.8 (C-
5), 122.4 (C-3Ј), 123.4 (C-5Ј), 125.6 (C-2ЈЈ, C-6ЈЈ), 127.7 (C-1ЈЈ),
129.5 (C-3ЈЈ, C-5ЈЈ), 137.4 (C-4Ј), 138.0 (C-4Ј), 148.3 (C-4), 149.7
(C-6Ј), 154.6 (C-2Ј) ppm. 15N NMR (51 MHz, CDCl3): δ = 247
(N-1), 313 (N-1Ј), 346 (N-3), 363 (N-2) ppm. HRMS (ESI+): calcd.
F, CF3) ppm. HRMS (ESI+): calcd. for C14H10F3N4 [M + H]+
+
for C15H15N4 [M + H]+ 251.1291; found 251.1291. C15H14N4
+
291.0852; found 291.0849. C14H9F3N4 (290.25): calcd. C 57.93, H
3.13, N 19.30; found C 57.67, H 2.97, N 19.21.
(250.30): calcd. C 71.98, H 5.64, N 22.38; found C 72.14, H 5.37,
N 22.13. The spectroscopic data are in agreement with those from
the literature.[50]
2-[1-(4-Bromophenyl)-1H-1,2,3-triazol-4-yl]pyridine (4Ka, R = Br):
1-Azido-4-bromobenzene (1K; 1.979 g, 10.0 mmol), 2-ethynylpyr-
idine (2a; 1.030 g, 10.0 mmol), MeOH/H2O (120/80 mL),
CuSO4·5H2O (124.0 mg, 0.5 mmol), sodium ascorbate (3.394 g,
2-{[4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]methyl}pyridine (5Ch,
R = OMe): 2-Picolyl azide (1C; 134.0 mg, 1.00 mmol), 4-ethynylanis-
ole (2h; 131.9 mg, 1.00 mmol), CuBr(PPh3)3 (3.0 mg, 0.003 mmol).
20.0 mmol). NH4Cl (200 mL), CH2Cl2 (4ϫ 200 mL), brine The crude product was recrystallized from ethyl acetate/light petro-
(200 mL). Brown solid (2.455 g, 82%). Rf (ethyl acetate) = 0.4, m.p. leum. Pale brown solid (207.6 mg, 78%). Rf (light petroleum/ethyl
190–191 °C. IR: ν = 3128, 3097, 3055, 1600, 1584, 1569, 1547, 1495,
1470, 1284, 1271, 1234, 1197, 1087, 1069, 1035, 1008, 817, 779,
acetate, 5:3) = 0.2, m.p. 72.5–75 °C (ethyl acetate/light petroleum).
IR: ν = 3669, 2988, 2901, 1737, 1498, 1455, 1433, 1414, 1365, 1251,
˜
˜
738, 703, 694, 659, 620 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1222, 1171, 1070, 1028, 835, 797, 748, 714, 700 cm–1. 1H NMR
7.27 (ddd, J = 7.6, 4.9, 1.1 Hz, 1 H, 5Ј-H), 7.70 (m, 4 H, 2ЈЈ-H, (500 MHz, [D6]DMSO): δ = 3.79 (s, 3 H, CH3O), 5.74 (s, 2 H, CH2),
3ЈЈ-H, 5ЈЈ-H, 6ЈЈ-H), 7.84 (dt, J = 7.7, 1.8 Hz, 1 H, 4Ј-H), 8.25 (dd,
6.99–7.03 (m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.33 (d, J = 7.7 Hz, 1 H, 3Ј-H),
J = 8.1, 1.0 Hz, 1 H, 3Ј-H), 8.59 (s, 1 H, 5-H), 8.62 (dt, J = 4.7, 7.34–7.39 (m, 1 H, 5Ј-H), 7.77–7.81 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 7.84
1.3 Hz, 1 H, 6Ј-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 119.7 (ddd, J = 7.7, 7.7, 1.7 Hz, 1 H, 4Ј-H), 8.55 (s, 1 H, 5-H), 8.54–8.57
(C-5), 120.5 (C-3Ј), 121.8 (C-2ЈЈ, C-6ЈЈ), 122.5 (C-1ЈЈ), 123.2 (C-5Ј), (m, 1 H, 6Ј-H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ = 54.5
133.0 (C-3ЈЈ, C-5ЈЈ), 135.9 (C-4ЈЈ), 137.0 (C-4Ј), 149.2 (C-4), 149.5 (CH2), 55.1 (CH3O), 114.3 (C-3ЈЈ, C-5ЈЈ), 121.3 (C-5), 122.2 (C-3Ј,
(C-6Ј), 149.7 (C-2Ј) ppm. 15N NMR (51 MHz, CDCl3): δ = 254 C-5Ј), 123.3 (C-1ЈЈ), 126.5 (C-2ЈЈ, C-6ЈЈ), 137.4 (C-4Ј), 146.4 (C-4),
(N-1), 302 (N-1Ј), 350 (N-3), 360 (N-2) ppm. HRMS (ESI+): calcd.
149.5 (C-6Ј), 155.1 (C-2Ј), 159.0 (C-4ЈЈ) ppm. 15N NMR ([D6]-
10
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Eur. J. Org. Chem. 0000, 0–0

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/KAP1
Date: 29-10-14 15:52:45
Pages: 16
1,2,3-Triazoles Tethered to Heterocycles
DMSO): δ = 247 (N-1), 313 (N-1Ј), 347 (N-3), 364 (N-2) ppm. benzene (2m; 125.5 mg, 0.85 mmol), CuBr(PPh3)3 (2.7 mg,
HRMS (ESI+): calcd. for C15H15N4O+ [M + H]+ 267.1240; found
267.1240. C15H14N4O (266.30): calcd. C 67.65, H 5.30, N 21.04;
0.003 mmol). The crude product was recrystallized from ethyl acet-
ate/light petroleum. Orange crystals (180.8 mg, 73%). Rf (light petro-
found C 67.59, H 5.19, N 20.68. The spectroscopic data are in agree- leum/ethyl acetate, 5:3) = 0.25, m.p. 142–144.5 °C (ethyl acetate/light
ment with those from the literature.[51]
petroleum). IR: ν = 3663, 3123, 2971, 2901, 1737, 1604, 1589, 1508,
˜
1340, 1318, 1229, 1107, 1075, 1046, 860, 852, 832, 752, 712, 700,
691 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 5.82 (s, 2 H, CH2),
7.36–7.42 (m, 1 H, 5Ј-H, 3Ј-H), 7.86 (ddd, J = 7.7, 7.7, 1.8 Hz, 1 H,
4Ј-H), 8.14–8.18 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.31–8.34 (m, 2 H, 3ЈЈ-H,
5ЈЈ-H), 8.55–8.57 (m, 1 H, 6Ј-H), 8.95 (s, 1 H, 5-H) ppm. 13C NMR
(126 MHz, [D6]DMSO): δ = 54.7 (CH2), 122.4 (C-3Ј), 123.4 (C-5Ј),
124.4 (C-5), 124.5 (C-3ЈЈ, C-5ЈЈ), 126.0 (C-2ЈЈ, C-6ЈЈ), 137.1 (C-1ЈЈ),
137.5 (C-4Ј), 144.6 (C-4), 146.6 (C-4ЈЈ), 149.5 (C-6Ј), 154.6 (C-2Ј)
ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 250 (N-1), 313 (N-1Ј),
349 (N-3), 367 (N-2), 371 (NO2) ppm. HRMS (ESI+): calcd. for
2-{[4-(4-Cyanophenyl)-1H-1,2,3-triazol-1-yl]methyl}pyridine (5 Ci, R
= CN): 2-Picolyl azide (1C; 134.0 mg, 1.00 mmol), 4-ethynylbenzo-
nitrile (2i; 127.0 mg, 1.00 mmol), CuBr(PPh3)3 (3.0 mg, 0.003 mmol).
The crude product was recrystallized from tBuOH. Yellow-brown
solid (229.3 mg, 88%). Rf (light petroleum/ethyl acetate, 5:3) = 0.2,
m.p. 159.0–160.5 °C (tBuOH). IR: ν = 3132, 3052, 2225, 1656, 1613,
˜
1588, 1457, 1427, 1412, 1223, 1183, 1074, 1046, 1020, 849, 815, 756,
713 cm–1. 1H NMR (500 MHz, CDCl3): δ = 5.72 (s, 2 H, CH2), 7.31
(m, 2 H, 3Ј-H, 5Ј-H), 7.77–7.64 (m, 3 H, 4Ј-H, 3ЈЈ-H, 5ЈЈ-H), 7.95
(d, J = 8.5 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.09 (s, 1 H, 5-H), 8.63 (br. s, 1
H, 6Ј-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 55.9 (CH2), 111.5
(C-1ЈЈ), 118.8 (CN), 121.4 (C-5), 122.8 (C-3Ј, C-5Ј), 123.7 (C-3Ј, C-
5Ј), 126.1 (C-2ЈЈ, C-6ЈЈ), 132.7 (C-3ЈЈ, C-5ЈЈ), 135.0 (C-4ЈЈ), 137.5 (C-
4Ј), 146.4 (C-4), 149.9 (C-6Ј), 153.9 (C-2Ј) ppm. 15N NMR (51 MHz,
CDCl3): δ = 247 (N-1), 311 (N-1Ј), 348 (N-3), 365 (N-2) ppm.
C14H12N5O2 [M + H]+ 282.0986; found 282.0991. C14H11N5O2
+
(281.27): calcd. C 59.78, H 3.94, N 24.90; found C 59.81, H 3.76, N
24.84. The spectroscopic data are in agreement with those from the
literature.[52]
N,N-Dimethyl-4-[1-(pyridin-2-ylmethyl)-1H-1,2,3-triazol-1-yl]aniline
(5Cn, R = NMe2): 2-Picolyl azide (1C; 132.0 mg, 1.00 mmol), 4-eth-
ynyl-N,N-dimethylaniline (2n; 140.5 mg, 0.97 mmol), CuBr(PPh3)3
(3.5 mg, 0.004 mmol). The crude product was recrystallized from
ethyl acetate/light petroleum. Pale yellow crystals (207.4 mg, 78%).
Rf (light petroleum/ethyl acetate, 5:3) = 0.25, m.p. 153–155 °C (ethyl
+
HRMS (ESI+): calcd. for C15H12N5 [M + H]+ 262.1087; found
262.1085. C15H11N5 (261.29): calcd. C 68.95, H 4.24, N 26.80; found
C 68.91, H 4.04, N 26.69.
2-({4-[4-(Trifluoromethyl)phenyl]-1H-1,2,3-triazol-1-yl}methyl)pyr-
idine (5Cj, R = CF3): 2-Picolyl azide (1C; 134.0 mg, 1.00 mmol), 4-
ethynyl-α,α,α-trifluorotoluene (2j; 170.1 mg, 1.00 mmol), CuBr-
(PPh3)3 (3.0 mg, 0.003 mmol). The crude product was recrystallized
from tBuOH. Bright brown solid (241.7 mg, 80%). Rf (light petro-
acetate/light petroleum). IR: ν = 3662, 2982, 2901, 1737, 1617, 1503,
˜
1459, 1434, 1362, 1228, 1195, 1067, 1048, 821, 782, 760, 749,
717 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 2.93 (s, 6 H, CH3),
5.71 (s, 2 H, CH2), 6.75–6.79 (m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.31 (d, J =
7.9 Hz, 1 H, 3Ј-H), 7.34–7.38 (m, 1 H, 5Ј-H), 7.65–7.69 (m, 2 H, 2ЈЈ-
H, 6ЈЈ-H), 7.83 (ddd, J = 7.7, 7.7, 1.8 Hz, 1 H, 4Ј-H), 8.55 (s, 1 H,
5-H), 8.55–8.57 (m, 1 H, 6Ј-H) ppm. 13C NMR (126 MHz, [D6]-
DMSO): δ = 40.0 (CH3), 54. 5 (CH2), 112.3 (C-3ЈЈ, C-5ЈЈ), 118.6 (C-
1ЈЈ), 120.4 (C-5), 122.1 (C-3Ј), 123.2 (C-5Ј), 126.1 (C-2ЈЈ, C-6ЈЈ),
137.4 (C-4Ј), 147.1 (C-4), 149.4 (C-6Ј), 150.0 (C-4ЈЈ), 155.2 (C-2Ј)
ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 48 [N(CH3)2], 246 (N-
1), 313 (N-1Ј), 345 (N-3), 363 (N-2) ppm. HRMS (ESI+): calcd. for
C16H18N5+ [M + H]+ 280.1557; found 280.1585. C16H17N5 (279.34):
calcd. C 68.79, H 6.13, N 25.07; found C 68.61, H 6.20, N 24.84. The
spectroscopic data are in agreement with those from the literature.[52]
leum/ethyl acetate, 5:3) = 0.2, m.p. 112–113.5 °C (tBuOH). IR: ν =
˜
3113, 3020, 1623, 1588, 1573, 1475, 1444, 1428, 1313, 1105, 1067,
1
1045, 843, 808, 749, 720, 686 cm–1. H NMR (500 MHz, CDCl3): δ
= 5.72 (s, 2 H, CH2), 7.29 (m, 2 H, 3Ј-H, 5Ј-H), 7.67 (d, J = 8.1 Hz,
2 H, 3ЈЈ-H, 5ЈЈ-H), 7.72 (dt, J = 7.7, 1.8 Hz, 1 H, 4Ј-H), 7.95 (d, J
= 8.0 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.05 (s, 1 H, 5-H), 8.63 (d, J = 3.9 Hz,
1 H, 6Ј-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 55.8 (CH2),
121.0 (C-5), 122.6 (C-3Ј), 123.6 (C-5Ј), 124.1 (q, J = 272 Hz, CF3),
125.8 (q, J = 4 Hz, C-3ЈЈ, C-5ЈЈ), 125.8 (C-2ЈЈ, C-6ЈЈ), 130.0 (q, J =
33 Hz, C-4ЈЈ), 134.0 (C-1ЈЈ), 137.5 (C-4Ј), 146.8 (C-4), 149.9 (C-6Ј),
154.1 (C-2Ј) ppm. 15N NMR (51 MHz, CDCl3): δ = 246 (N-1), 311
(N-1Ј), 347 (N-3), 365 (N-2) ppm. 19F NMR (471 MHz, CDCl3): δ
+
= –62.6 (s, 3 F, CF3) ppm. HRMS (ESI+): calcd. for C15H12F3N4
[M + H]+ 305.1009; found 305.1007. C15H11F3N4 (304.27): calcd. C
59.21, H 3.64, N 18.41; found C 59.32, H 3.41, N 18.40.
2-[(4-Phenyl-1H-1,2,3-triazol-1-yl)methyl]pyrazine (5Df, R = H): 2-
(Azidomethyl)pyrazine (1D; 134.6 mg, 1.00 mmol), phenylacetylene
(2f; 102.1 mg, 1.00 mmol), CuBr(PPh3)3 (3.5 mg, 0.004 mmol). The
crude product was recrystallized from MeOH. Bright brown crystals
(141.3 mg, 60%). Rf (light petroleum/ethyl acetate, 5:3) = 0.25, m.p.
2-{[4-(4-Chlorophenyl)-1H-1,2,3-triazol-1-yl]methyl}pyridine (5Cl, R
= Cl): 2-Picolyl azide (1C; 134.0 mg, 1.00 mmol), 4-ethynylchloro-
benzene (2l; 136.6 mg, 1.00 mmol), CuBr(PPh3)3 (3.0 mg,
0.003 mmol). The crude product was recrystallized from tBuOH.
Brown solid (217.2 mg, 80%). Rf (light petroleum/ethyl acetate, 5:3)
134–137 °C (MeOH). IR: ν = 3668, 2988, 2901, 1737, 1409, 1222,
˜
1075, 1050, 1020, 782, 763, 695 cm–1. 1H NMR (500 MHz, [D6]-
DMSO): δ = 5.87 (s, 2 H, CH2), 7.31–7.38 (m, 1 H, 4ЈЈ-H), 7.43–
7.48 (m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.85–7.88 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.63–
8.67 (m, 2 H, 5Ј-H, 6Ј-H), 8.69 (s, 1 H, 5-H), 8.77 (br. s, 1 H, 3Ј-H)
ppm. 13C NMR (126 MHz, [D6]DMSO): δ = 52.2 (CH2), 122.4 (C-
5), 125.2 (C-2ЈЈ, C-6ЈЈ), 128.0 (C-4ЈЈ), 129.0 (C-3ЈЈ, C-5ЈЈ), 130.6 (C-
1ЈЈ), 144.0 (C-3Ј), 144.5 (C-5Ј), 144.6 (C-6Ј), 146.5 (C-4), 150.6 (C-
2Ј) ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 246 (N-1), 330 (N-
1Ј or N-4Ј), 348 (N-3), 364 (N-2) ppm. HRMS (ESI+): calcd. for
= 0.2, m.p. 119.5–121.5 °C (tBuOH). IR: ν = 3127, 3090, 1598, 1586,
˜
1571, 1547, 1457, 1434, 1407, 1222, 1106, 845, 752, 706 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 5.70 (s, 2 H, CH2), 7.28 (m, 2 H, 3Ј-
H, 5Ј-H), 7.38 (d, J = 8.5 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.71 (dt, J = 7.7,
1.8 Hz, 1 H, 4Ј-H), 7.77 (d, J = 8.5 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 7.94 (s,
1 H, 5-H), 8.62 (dt, J = 4.7, 1.4 Hz, 1 H, 6Ј-H) ppm. 13C NMR
(126 MHz, CDCl3): δ = 55.8 (CH2), 120.2 (C-5), 122.6 (C-3Ј), 123.5
(C-5Ј), 127.0 (C-2ЈЈ, C-6ЈЈ), 129.0 (C-1ЈЈ), 129.0 (C-3ЈЈ, C-5ЈЈ), 133.9
(C-4ЈЈ), 137.4 (C-4Ј), 147.2 (C-4), 149.8 (C-6Ј), 154.3 (C-2Ј) ppm.
15N NMR (51 MHz, CDCl3): δ = 246 (N-1), 311 (N-1Ј), 346 (N-3),
C13H12N5 [M + H]+ 238.1087; found 238.1090. C13H11N5·0.1H2O:
+
calcd. C 65.31, H 4.72, N 29.30; found C 65.55, H 4.62, N 28.91.
364 (N-2) ppm. HRMS (ESI+): calcd. for C14H12ClN4 [M + H]+
+
2-{[4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]methyl}pyrazine (5Dh,
R = OMe): 2-(Azidomethyl)pyrazine (1D; 134.6 mg, 1.00 mmol), 4-
ethynylanisole (2h; 131.9 mg, 1.00 mmol), CuBr(PPh3)3 (3.5 mg,
271.0745; found 271.0746. C14H11ClN4 (270.72): calcd. C 62.11, H
4.10, N 20.70; found C 62.30, H 3.88, N 20.60.
2-{[4-(4-Nitrophenyl)-1H-1,2,3-triazol-1-yl]methyl}pyridine (5Cm, R 0.004 mmol). The crude product was recrystallized from MeOH.
= NO2): 2-Picolyl azide (1C; 129.3 mg, 0.97 mmol), 4-ethynyl-nitro- Brown crystals (183.5 mg, 68%). Rf (light petroleum/ethyl acetate,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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11

Job/Unit: O43100
/KAP1
Date: 29-10-14 15:52:45
Pages: 16
A. Bolje, D. Urankar, J. Kosˇmrlj
5:3) = 0.25, m.p. 128–131 °C (MeOH). IR: ν = 3661, 2987, 2966, NMR (126 MHz, [D6]DMSO): δ = 53.4 (CH2), 119.4 (C-5Ј), 122.8
FULL PAPER
˜
2901, 1738, 1615, 1496, 1458, 1405, 1361, 1301, 1243, 1224, 1048,
(C-5), 125.2 (C-2ЈЈ, C-6ЈЈ), 128.0 (C-4ЈЈ), 129.0 (C-3ЈЈ, C-5ЈЈ), 130.6
(C-1ЈЈ), 146.6 (C-4), 158.1 (C-6Ј), 158.5 (C-2Ј), 163.6 (C-4Ј) ppm.
1
1027, 1020, 837, 802, 774 cm–1. H NMR (500 MHz, [D6]DMSO):
δ = 3.79 (s, 3 H, OCH3), 5.84 (s, 2 H, CH2), 6.99–7.03 (m, 2 H, 3ЈЈ- 15N NMR (51 MHz, [D6]DMSO): δ = 244 (N-1), 291 (N-1Ј or N-
+
H, 5ЈЈ-H), 7.76–7.80 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.56 (s, 1 H, 5-H), 8.63–
3Ј), 349 (N-3), 365 (N-2) ppm. HRMS (ESI+): calcd. for C13H12N5
8.67 (m, 2 H, 5Ј-H, 6Ј-H), 8.76 (br. s, 1 H, 3Ј-H) ppm. 13C NMR [M + H]+ 238.1087; found 238.1087. C13H11N5·0.1H2O: C 65.31, H
(126 MHz, [D6]DMSO): δ = 52.2 (CH2), 55.2 (OCH3), 114.3 (C-3ЈЈ,
C-5ЈЈ), 121.4 (C-5), 123.2 (C-1ЈЈ), 126.5 (C-2ЈЈ, C-6ЈЈ), 144.0 (C-3Ј),
4.72, N 29.30; found C 65.04, H 4.48, N 28.92.
4-{[4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]methyl}pyrimidine
(5Eh, R = OMe): 4-(Azidomethyl)pyrimidine (1E; 134.6 mg,
1.00 mmol), 4-ethynylanisole (2h; 131.9 mg, 1.00 mmol), CuBr(PPh3)3
(9.0 mg, 0.01 mmol). The crude product was recrystallized from ethyl
acetate. Bright brown powder (174.1 mg, 68%). Rf (light petroleum/
144.5 (C-5Ј, C-6Ј), 146.5 (C-4), 150.7 (C-2Ј), 159.0 (C-4ЈЈ) ppm. 15
N
NMR (51 MHz, [D6]DMSO): δ = 245 (N-1), 331 (N-1Ј or N-4Ј),
347 (N-3), 363 (N-2) ppm. HRMS (ESI+): calcd. for C14H14N5O+
[M + H]+ 268.1193; found 268.1195. C14H13N5O (267.29): calcd. C
62.91, H 4.90, N 26.60; found C 62.87, H 4.82, N 25.91.
ethyl acetate, 5:3) = 0.2, m.p. 123–125 °C (ethyl acetate). IR: ν =
˜
2-{[4-(4-Nitrophenyl)-1H-1,2,3-triazol-1-yl]methyl}pyrazine (5Dm, R 3667, 2987, 2971, 2954, 2901, 1737, 1582, 1558, 1498, 1395, 1290,
= NO2): 2-(Azidomethyl)pyrazine (1D; 134.6 mg, 1.00 mmol), 4-eth- 1248, 1216, 1176, 1077, 1044, 1029, 830, 795, 719, 649, 624 cm–1. 1H
ynyl-nitrobenzene (2m; 147.7 mg, 1.00 mmol), CuBr(PPh3)3 (3.5 mg,
0.004 mmol). The crude product was recrystallized from ethyl acet-
NMR (500 MHz, [D6]DMSO): δ = 3.79 (s, 3 H, OCH3), 5.83 (s, 2
H, CH2), 7.01–7.04 (m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.38 (d, J = 5.2 Hz, 1 H,
ate. Orange-brown powder (149.0 mg, 52%). Rf (light petroleum/ 5Ј-H), 7.78–7.82 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.58 (s, 1 H, 5-H), 8.83 (br.
ethyl acetate, 5:3) = 0.25, m.p. 168–172 °C (ethyl acetate). IR: ν =
d, J = 5.1 Hz, 1 H, 6Ј-H), 9.17 (br. s, 1 H, 2Ј-H) ppm. 13C NMR
(126 MHz, [D6]DMSO): δ = 53.4 (CH2), 55.2 (OCH3), 114.3 (C-3ЈЈ,
˜
3664, 2987, 2972, 2901, 1738, 1606, 1508, 1415, 1356, 1339, 1235,
1080, 1063, 1048, 1019, 976, 863, 853, 831, 755, 710, 690, 670 cm–1. C-5ЈЈ), 119.4 (C-5Ј), 121.8 (C-5), 123.2 (C-1ЈЈ), 126.6 (C-2ЈЈ, C-6ЈЈ),
1H NMR (500 MHz, [D6]DMSO): δ = 5.92 (s, 2 H, CH2), 8.13–8.17
146.6 (C-4), 158.2 (C-6Ј), 158.5 (C-2Ј), 159.1 (C-4ЈЈ), 163.7 (C-4Ј)
(m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.31–8.34 (m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 8.64–8.68 ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 243 (N-1), 291 (N-1Ј or
(m, 2 H, 5Ј-H, 6Ј-H), 8.81 (d, J = 1.0 Hz, 1 H, 3Ј-H), 8.96 (s, 1 H,
5-H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ = 52.3 (CH2), 124.4
(C-3ЈЈ, C-5ЈЈ), 124.6 (C-5), 126.0 (C-2ЈЈ, C-6ЈЈ), 137.0 (C-1ЈЈ), 144.1
(C-3Ј), 144.6 (C-5Ј, C-6Ј), 144.7 (C-4), 146.7 (C-4ЈЈ), 150.3 (C-2Ј)
ppm. 15N NMR (51 MHz, [D6]DMSO): δ = 248 (N-1), 330 (N-1Ј or
N-4Ј), 350 (N-3), 366 (N-2), 371 (NO2) ppm. HRMS (ESI+): calcd.
for C14H14N5O+ [M + H]+ 283.0938; found 283.0943. C14H13N5O
(267.29): calcd. C 55.32, H 3.57, N 29.77; found C 55.02, H 3.41, N
29.49.
N-3Ј), 348 (N-3), 364 (N-2) ppm. HRMS (ESI+): calcd. for
C14H14N5O+ [M + H]+ 268.1193; found 268.1188.
4-{[4-(4-Nitrophenyl)-1H-1,2,3-triazol-1-yl]methyl}pyrimidine (5Em,
R = NO2): 4-(Azidomethyl)pyrimidine (1E; 134.6 mg, 1.00 mmol),
4-ethynyl-nitrobenzene (2m; 147.7 mg, 1.00 mmol), CuBr(PPh3)3
(9.0 mg, 0.01 mmol). The crude product was recrystallized from
CH2Cl2. Yellow crystals (160.9 mg, 56%). Rf (light petroleum/ethyl
acetate, 5:3) = 0.2, m.p. 160–162 °C (CH Cl ). IR: ν = 3667, 2977,
˜
2
2
2901, 1737, 1579, 1515, 1348, 1356, 1070, 1056, 798, 740, 686 cm–1.
2-{[4-[4-(Dimethylamino)phenyl]-1H-1,2,3-triazol-1-yl]meth- 1H NMR (500 MHz, [D6]DMSO): δ = 5.91 (s, 2 H, CH2), 7.47 (br.
yl}pyrazine (5Dn, R = NMe2): 2-(Azidomethyl)pyrazine (1D; d, J = 4.9 Hz, 1 H, 5Ј-H), 8.15–8.18 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.32–
134.6 mg, 1.00 mmol), 4-ethynyl-N,N-dimethylaniline (2n; 144.8 mg, 8.36 (m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 8.86 (br. d, J = 4.9 Hz, 1 H, 6Ј-H), 8.96
1.00 mmol), CuBr(PPh3)3 (3.5 mg, 0.004 mmol). The crude product
was recrystallized from MeOH/water. Red-brown crystals (203.4 mg,
73%). Rf (light petroleum/ethyl acetate, 5:3) = 0.25, m.p. 173–175 °C
(s, 1 H, 5-H), 9.17 (br. s, 1 H, 2Ј-H) ppm. 13C NMR (126 MHz, [D6]-
DMSO): δ = 53.5 (CH2), 119.6 (C-5Ј), 124.5 (C-3ЈЈ, C-5ЈЈ), 124.9 (C-
5), 126.0 (C-2ЈЈ, C-6ЈЈ), 137.0 (C-1ЈЈ), 144.7 (C-4), 146.7 (C-4ЈЈ),
158.2 (C-6Ј), 158.6 (C-2Ј), 163.2 (C-4Ј) ppm. 15N NMR (51 MHz,
(MeOH/water). IR: ν = 3662, 2972, 2901, 1738, 1618, 1508, 1409,
˜
1
1364, 1226, 1199, 1067, 1051, 1019, 946, 819, 779, 672 cm–1. H [D6]DMSO): δ = 246 (N-1), 291 (N-1Ј or N-3Ј), 350 (N-3), 367
NMR (500 MHz, [D6]DMSO): δ = 2.93 (s, 6 H, CH3), 5.81 (s, 2 H, (N-2), 371 (NO2) ppm. HRMS (ESI+): calcd. for C14H14N5O+ [M
CH2), 6.75–6.79 (m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.64–7.67 (m, 2 H, 2ЈЈ-H, + H]+ 283.0938; found 283.0935.
6ЈЈ-H), 8.45 (s, 1 H, 5-H), 8.63–8.65 (m, 2 H, 5Ј-H, 6Ј-H), 8.74 (br.
4-{[4-[4-(Dimethylamino)phenyl]-1H-1,2,3-triazol-1-yl]meth-
s, 1 H, 3Ј-H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ = 40.0
yl}pyrimidine (5En, R = NMe2): 4-(Azidomethyl)pyrimidine (1E;
(CH3), 52.1 (CH2), 112.3 (C-3ЈЈ, C-5ЈЈ), 118.5 (C-1ЈЈ), 120.4 (C-5),
134.6 mg, 1.00 mmol), 4-ethynyl-N,N-dimethylaniline (2n; 144.8 mg,
126.1 (C-2ЈЈ, C-6ЈЈ), 144.0 (C-3Ј), 144.5 (C-5Ј, C-6Ј), 147.2 (C-4),
1.00 mmol), CuBr(PPh3)3 (9.0 mg, 0.01 mmol). The crude product
was recrystallized from ethyl acetate. Bright brown crystals
(207.9 mg, 75%). Rf (light petroleum/ethyl acetate, 5:3) = 0.2, m.p.
150.0 (C-4ЈЈ), 150.8 (C-2Ј) ppm. 15N NMR (51 MHz, [D6]DMSO):
δ = 48 [N(CH3)2], 245 (N-1), 331 (N-1Ј or N-4Ј), 346 (N-3), 363 (N-
2) ppm. HRMS (ESI+): calcd. for C15H17N6 [M + H]+ 281.1509;
+
159–162 °C (ethyl acetate). IR: ν = 3662, 2987, 2972, 2901, 1737,
˜
found 281.1509. C15H16N6 (280.33): calcd. C 64.43, H 5.75, N 29.98;
found C 64.53, H 5.71, N 29.55.
1618, 1577, 1552, 1597, 1447, 1421, 1380, 1352, 1223, 1203, 1075,
1
1046, 946, 808, 782, 736, 671, 665 cm–1. H NMR (500 MHz, [D6]-
4-[(4-Phenyl-1H-1,2,3-triazol-1-yl)methyl]pyrimidine (5Ef, R = H): 4- DMSO): δ = 2.93 (s, 6 H, CH3), 5.80 (s, 2 H, CH2), 6.79 (d, J =
(Azidomethyl)pyrimidine (1E; 134.6 mg, 1.00 mmol), phenylacetyl- 8.8 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.35 (d, J = 5.1 Hz, 1 H, 5Ј-H), 7.68 (d,
ene (2f; 102.1 mg, 1.00 mmol), CuBr(PPh3)3 (9.0 mg, 0.01 mmol). J = 8.8 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.46 (s, 1 H, 5-H), 8.83 (br. d, J =
The crude product was recrystallized from ethyl acetate. Bright 5.1 Hz, 1 H, 6Ј-H), 9.17 (br. s, 1 H, 2Ј-H) ppm. 13C NMR (126 MHz,
brown powder (182.4 mg, 78%). Rf (light petroleum/ethyl acetate,
[D6]DMSO): δ = 40.0 (CH3), 53.4 (CH2), 112.3 (C-3ЈЈ, C-5ЈЈ), 118.4
(C-1ЈЈ), 119.3 (C-5Ј), 120.8 (C-5), 126.1 (C-2ЈЈ, C-6ЈЈ), 147.3 (C-4),
150.1 (C-4ЈЈ), 158.1 (C-6Ј), 158.5 (C-2Ј), 163.8 (C-4Ј) ppm. 15N
NMR (51 MHz, [D6]DMSO): δ = 48 [N(CH3)2], 242 (N-1), 291 (N-
1Ј or N-3Ј), 347 (N-3), 363 (N-2) ppm. HRMS (ESI+): calcd. for
5:3) = 0.2, m.p. 103–104 °C (ethyl acetate). IR: ν = 3662, 2987, 2969,
˜
2901, 1737, 1577, 1550, 1382, 1353, 1224, 1078, 1066, 1050, 821, 767,
700 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 5.86 (s, 2 H, CH2),
7.33–7.37 (m, 1 H, 4ЈЈ-H), 7.40 (d, J = 5 Hz, 1 H, 5Ј-H), 7.44–7.48
(m, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.86–7.90 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.70 (s, 1 C15H17N6+ [M + H]+ 281.1509; found 281.1520. C15H16N6 (280.33):
H, 5-H), 8.85 (br. s, 1 H, 6Ј-H), 9.18 (br. s, 1 H, 2Ј-H) ppm. 13C
calcd. C 64.43, H 5.75, N 29.98; found C 64.06, H 5.62, N 29.62.
12
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O43100
/KAP1
Date: 29-10-14 15:52:45
Pages: 16
1,2,3-Triazoles Tethered to Heterocycles
General Procedure for the Synthesis of (1-Aryl-1H-1,2,3-triazol-4-yl)- J = 8.4 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 8.20 (s, 1 H, 5-H), 8.62 (ddd, J =
(pyridin-2-yl)methyl Acetates 6Ј: A mixture of phenyl azide 1F, 1H,
4.9, 1.9, 1.0 Hz, 1 H, 6Ј-H) ppm. 13C NMR (126 MHz, CDCl3): δ
or 1J and 1-(pyridin-2-yl)prop-2-yn-1-yl acetate 2cЈ was cooled to = 21.1 (CH3CO), 70.7 (CH), 120.5 (C-2ЈЈ, C-6ЈЈ), 121.5 (C-5), 122.4
ca. 10 °C in an ice-water bath, and CuBr(PPh3)3 was added to the
stirred mixture. The reaction mixture was stirred at room tempera-
ture for 30 min (until TLC analysis indicated compete consumption
of starting material), during which time the reaction mixture dark-
(C-3Ј), 123.5 (C-5Ј), 123.5 (q, J = 272 Hz, CF3), 126.2 (C-1ЈЈ), 127.1
(q, J = 4 Hz, C-3ЈЈ, C-5ЈЈ), 130.9 (q, J = 33 Hz, C-4ЈЈ), 137.2 (C-4Ј),
146.9 (C-4), 149.7 (C-6Ј), 156.7 (C-2Ј), 169.9 (CH3CO) ppm. 15N
NMR (51 MHz, CDCl3): δ = 252 (N-1), 307 (N-1Ј), 355 (N-3), 361
ened and became solid. The products (i.e., 6FcЈ, 6HcЈ, and 6JcЈ) (N-2) ppm. 19F NMR (471 MHz, CDCl3): δ = –62.6 (s, 3 F, CF3)
were purified by column chromatography on silica gel using a mix-
ture of ethyl acetate and light petroleum (2:1) as eluent, followed by found 363.1059. C17H13F3N4O2 (362.31): calcd. C 56.38, H 3.64, N
ppm. HRMS (ESI+): calcd. for C17H14F3N4O2+ [M + H]+ 363.1063;
recrystallization from a mixture of EtOH and water. The quantities
used in the above procedure, and spectral and analytical data are
given below.
15.46; found C 56.78, H 4.04, N 15.33.
General Procedure for the Synthesis of Triazoles 6: A mixture of acet-
ate 6FcЈ, 6HcЈ, or 6JcЈ and Pd/C (10%) in EtOH was hydrogenated
in a Parr apparatus under H2 (50 psi) for 24 h. The solvent was evap-
orated, and the residue was dissolved in ethyl acetate (10 mL). Water
and saturated aqueous NaHCO3 were added, and the product was
extracted with ethyl acetate. The combined organic layers were dried
with anhydrous sodium sulfate, and the solvents were evaporated to
dryness to give pure 6Fc, 6Hc, or 6Jc. The quantities used in the
above procedure, and the spectral and analytical data are given be-
low.
(1-Phenyl-1H-1,2,3-triazol-4-yl)(pyridin-2-yl)methyl Acetate (6FcЈ, R
= H): Azidobenzene (1F; 119.1 mg, 1.00 mmol), 1-(pyridin-2-yl)-
prop-2-yn-1-yl acetate (2cЈ; 175.2 mg, 1.0 mmol), CuBr(PPh3)3
(2.7 mg, 0.003 mmol). White solid (213.0 mg, 73%). Rf (light petro-
leum/ethyl acetate, 1:2) = 0.3, m.p. 97.5–99.0 °C (EtOH/water). IR:
ν = 3131, 1737, 1586, 1505, 1468, 1433, 1373, 1229, 1033, 985, 931,
˜
1
834, 755, 718, 689 cm–1. H NMR (500 MHz, CDCl3): δ = 2.20 (s,
3 H, CH3CO), 7.11 (s, 1 H, CH), 7.27 (m, 1 H, 5Ј-H), 7.44 (m, 1 H,
4ЈЈ-H), 7.51 (dd, J = 8.6, 7.1 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.68 (dt, J =
8.0, 1.1 Hz, 1 H, 3Ј-H), 7.71 (m, 2 H, 2ЈЈ-H, 6ЈЈ-H), 7.77 (dt, J =
7.7, 1.8 Hz, 1 H, 4Ј-H), 8.11 (s, 1 H, 5-H), 8.62 (ddd, J = 4.7, 1.9,
1.1 Hz, 1 H, 6Ј-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 21.1
(CH3CO), 70.8 (CH), 120.6 (C-3ЈЈ, C-5ЈЈ), 121.7 (C-5), 122.3 (C-3Ј),
123.3 (C-5Ј), 128.9 (C-4ЈЈ), 129.7 (C-2ЈЈ, C-6ЈЈ), 136.9 (C-1ЈЈ), 137.1
(C-4Ј), 146.3 (C-4), 149.6 (C-6Ј), 156.9 (C-2Ј), 170.0 (CH3CO) ppm.
15N NMR (51 MHz, CDCl3): δ = 255 (N-1), 307 (N-1Ј), 352 (N-3),
2-[(1-Phenyl-1H-1,2,3-triazol-4-yl)methyl]pyridine (6Fc, R = H): (1-
Phenyl-1H-1,2,3-triazol-4-yl)(pyridin-2-yl)methyl acetate (6FcЈ;
294.4 mg, 1.00 mmol), Pd/C (29.4 mg), EtOH (40 mL). Water
(80 mL), NaHCO3 (30 mL), ethyl acetate (3ϫ 60 mL). White solid
(185.0 mg, 78%). Rf (light petroleum/ethyl acetate, 1:2) = 0.2, m.p.
67–69 °C. IR: ν = 3131, 1666, 1607, 1495, 1460, 1433, 1370, 1198,
˜
1133, 1009, 957, 918, 830, 789, 748, 680 cm–1. H NMR (500 MHz,
1
CDCl3): δ = 4.37 (s, 2 H, CH2), 7.19 (ddd, J = 7.5, 4.9, 1.1 Hz, 1 H,
5Ј-H), 7.38 (d, J = 7.9 Hz, 1 H, 3Ј-H), 7.44 (m, 1 H, 4ЈЈ-H), 7.52
(ddd, J = 7.9, 6.9, 1.4 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.66 (dt, J = 7.7,
1.9 Hz, 1 H, 4Ј-H), 7.73 (dd, J = 8.5, 1.3 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H),
7.89 (s, 1 H, 5-H), 8.58 (ddd, J = 4.9, 1.9, 1.0 Hz, 1 H, 6Ј-H) ppm.
13C NMR (126 MHz, CDCl3): δ = 35.0 (CH2), 120.1 (C-5), 120.5
(C-2ЈЈ, C-6ЈЈ), 121.8 (C-5Ј), 123.4 (C-3Ј), 128.6 (C-4ЈЈ), 129.7 (C-3ЈЈ,
C-5ЈЈ), 136.9 (C-4Ј), 137.2 (C-1ЈЈ), 146.4 (C-4), 149.5 (C-6Ј), 158.6
(C-2Ј) ppm. 15N NMR (51 MHz, CDCl3): δ = 254 (N-1), 310 (N-
1Ј), 352 (N-3) ppm. HRMS (ESI+): calcd. for C14H12N4+ [M + H]+
237.1135; found 237.1146. C14H11N4 (235.27): calcd. C 71.17, H
5.12, N 23.71; found C 70.96, H 5.09, N 23.58.
+
360 (N-2) ppm. HRMS (ESI+): calcd. for C16H15N4O2 [M + H]+
295.1190; found 295.1183. C16H14N4O2 (294.31): calcd. C 65.30, H
4.79, N 19.04; found C 65.24, H 4.51, N 19.04.
[1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl](pyridin-2-yl)methyl Acet-
ate (6ЈHcЈ, R = OMe): 1-Azido-4-methoxybenzene (1H; 149.2 mg,
1.00 mmol), 1-(pyridin-2-yl)prop-2-yn-1-yl acetate (2cЈ; 175.2 mg,
1.00 mmol), CuBr(PPh3)3 (2.7 mg, 0.003 mmol). White solid
(266.0 mg, 83%). Rf (light petroleum/ethyl acetate, 1:2) = 0.3, m.p.
97.5–99.5 °C (EtOH/water). IR: ν = 3143, 2963, 2834, 1735, 1590,
˜
1520, 1471, 1435, 1372, 1260, 1025, 970, 832, 809, 758, 711,
1
617 cm–1. H NMR (500 MHz, CDCl3): δ = 2.20 (s, 3 H, CH3CO),
3.86 (s, 3 H, CH3O), 7.00 (d, J = 9.0 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.10 (s,
1 H, CH), 7.26 (m, 1 H, 5Ј-H), 7.60 (d, J = 9.0 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-
H), 7.67 (dt, J = 7.8, 1.1 Hz, 1 H, 3Ј-H), 7.76 (dt, J = 7.7, 1.8 Hz,
1 H, 4Ј-H), 8.02 (s, 1 H, 5-H), 8.62 (ddd, J = 4.7, 1.8, 0.9 Hz, 1 H,
6Ј-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 21.2 (CH3CO), 55.6
(CH3O), 70.9 (CH), 114.7 (C-3ЈЈ, C-5ЈЈ), 121.8 (C-5), 122.3 (C-3Ј, C-
2ЈЈ, C-6ЈЈ), 123.3 (C-5Ј), 130.4 (C-1ЈЈ), 137.1 (C-4Ј), 146.1 (C-4),
149.6 (C-6Ј), 157.0 (C-2Ј), 159.9 (C-4ЈЈ), 170.0 (CH3CO) ppm. 15N
NMR (51 MHz, CDCl3): δ = 254 (N-1), 307 (N-1Ј), 351 (N-3) ppm.
2-{[1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl]methyl}pyridine (6Hc,
R = OMe): [1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl](pyridin-2-
yl)methyl acetate (6HcЈ; 324.0 mg, 1.00 mmol), Pd/C (32.4 mg),
EtOH (40 mL). Water (80 mL), NaHCO3 (30 mL), ethyl acetate (3ϫ
60 mL). White solid (242 mg, 91%). Rf (light petroleum/ethyl acet-
ate, 1:2) = 0.2, m.p. 95–96 °C. IR: ν = 3056, 1617, 1549, 1518, 1478,
˜
1323, 1307, 1279, 1250, 1228, 1187, 1066, 1050, 835, 756, 718,
1
613 cm–1. H NMR (500 MHz, CDCl3): δ = 3.85 (s, 3 H, CH3O),
4.34 (s, 2 H, CH2), 6.99 (d, J = 9.0 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H), 7.17 (dd,
J = 7.4, 4.8 Hz, 1 H, 5Ј-H), 7.35 (d, J = 7.8 Hz, 1 H, 3Ј-H), 7.62
(m, 3 H, 4Ј-H, 2ЈЈ-H, 6ЈЈ-H), 7.79 (s, 1 H, 5-H), 8.56 (d, J = 4.3 Hz,
1 H, 6Ј-H) ppm. 13C NMR (126 MHz, CDCl3): δ = 35.1 (CH2), 55.6
(CH3O), 114.7 (C-3ЈЈ, C-5ЈЈ), 120.3 (C-5), 121.7 (C-5Ј), 122.1 (C-2ЈЈ,
C-6ЈЈ), 123.4 (C-3Ј), 130.7 (C-1ЈЈ), 136.9 (C-4Ј), 146.2 (C-4), 149.5
(C-6Ј), 158.7 (C-2Ј), 159.7 (C-4ЈЈ) ppm. 15N NMR (51 MHz,
CDCl3): δ = 254 (N-1), 310 (N-1Ј), 351 (N-3), 358 (N-2) ppm.
HRMS (ESI+): calcd. for C15H15N4O+ [M + H]+ 267.1246; found
267.1239. C15H14N4O (266.30): calcd. C 67.65, H 5.30, N 21.04;
found C 67.48, H 5.28, N 20.89.
HRMS (ESI+): calcd. for C17H17N4O3 [M + H]+ 325.1295; found
+
325.1289. C17H16N4O3 (324.34): calcd. C 62.95, H 4.97, N 17.27;
found C 62.98, H 4.73, N 17.05.
Pyridin-2-yl{1-[4-(trifluoromethyl)phenyl]-1H-1,2,3-triazol-4-
yl}methyl Acetate (6JcЈ, R = CF3): 1-Azido-4-(trifluoromethyl)benz-
ene (1J; 187.1 mg, 1.00 mmol), 1-(pyridin-2-yl)prop-2-yn-1-yl acetate
(2cЈ; 175.2 mg, 1.00 mmol), CuBr(PPh3)3 (2.7 mg, 0.003 mmol).
White solid (247.8 mg, 68%). Rf (light petroleum/ethyl acetate, 1:2)
= 0.3, m.p. 88.5–90.5 °C (EtOH/water). IR: ν = 3163, 3090, 1726,
˜
1615, 1590, 1558, 1320, 1268, 1237, 1161, 1123, 1110, 1047, 856, 825,
1
763, 745, 679 cm–1. H NMR (500 MHz, CDCl3): δ = 2.21 (s, 3 H,
2-({1-[4-(Trifluoromethyl)phenyl]-1H-1,2,3-triazol-4-yl}methyl)pyr-
idine (6Jc, R = CF3): Pyridin-2-yl{1-[4-(trifluoromethyl)phenyl]-1H-
CH3CO), 7.12 (s, 1 H, CH), 7.28 (m, 1 H, 5Ј-H), 7.68 (dt, J = 7.9,
1.1 Hz, 1 H, 3Ј-H), 7.85–7.73 (m, 3 H, 4Ј-H, 3ЈЈ-H, 5ЈЈ-H), 7.88 (d, 1,2,3-triazol-4-yl}methyl acetate (6JcЈ; 362.0 mg, 1.00 mmol), Pd/C
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A. Bolje, D. Urankar, J. Kosˇmrlj
FULL PAPER
ist, Dalton Trans. 2013, 42, 7019–7031; o) T. Biet, N. Avarvari,
CrystEngComm 2014, 16, 6612–6620.
B. Happ, D. Escudero, M. D. Hager, C. Friebe, A. Winter, H.
Görls, E. Altunta, L. González, U. S. Schubert, J. Org. Chem.
2010, 75, 4025–4038.
a) F. A. Jalón, B. R. Manzano, F. Gómez-de la Torre, A. M.
Guerrero, A. M. Rodríguez, in: Targets in Heterocyclic Systems,
Chemistry and Properties, vol. 3 (Eds.: A. O. Attanasi, D. Spi-
nelli), Roma, Italy, 1999, p. 399–438; b) C. Pettinari, R. Pettinari,
Coord. Chem. Rev. 2005, 249, 663–691.
A. Bolje, J. Kosˇmrlj, Org. Lett. 2013, 15, 5084–5087.
For selected reviews, see: a) H. Struthers, T. L. Mindt, R. Schibli,
Dalton Trans. 2010, 39, 675–696; b) J. D. Crowley, A.-L. Lee,
K. J. Kilpin, Aust. J. Chem. 2011, 64, 1118–1132; c) J. D. Crow-
ley, D. A. McMorran, ‘Click-Triazole’ Coordination Chemistry:
Exploiting 1,4-Disubstituted 1,2,3-Triazoles as Ligands, in: Topics
in Heterocyclic Chemistry, vol. 28 (Ed.: J. Kosˇmrlj), Springer,
Berlin, Heidelberg, Germany, 2012, p. 31–83; d) D.
Schweinfurth, N. Deibel, F. Weisser, B. Sarkar, Nachr. Chem.
2011, 59, 937–941; e) L. Liang, D. Astruc, Coord. Chem. Rev.
2011, 255, 2933–2945; f) G. Aromia, L. A. Barriosa, O. Rou-
beaub, P. Gameza, Coord. Chem. Rev. 2011, 255, 485–546; g)
K. F. Donnelly, A. Petronilho, M. Albrecht, Chem. Commun.
2013, 49, 1145–1159; h) B. Schulze, U. S. Schubert, Chem. Soc.
Rev. 2014, 43, 2522–2571; i) J. M. Aizpurua, R. M. Fratila, Z.
Monasterio, N. Pérez-Esnaola, E. Andreieff, A. Irastorza, M.
Sagartzazu-Aizpurua, New J. Chem. 2014, 38, 474–480.
A. Bolje, S. Hohloch, D. Urankar, A. Pevec, M. Gazvoda, B.
Sarkar, J. Kosˇmrlj, Organometallics 2014, 33, 2588–2598.
J. H. Boyer, D. I. McCane, J. W. McCarville, A. T. Tweedie, J.
Am. Chem. Soc. 1953, 75, 5298–5300.
(36.2 mg), EtOH (40 mL). Water (80 mL), NaHCO3 (30 mL), ethyl
acetate (3ϫ 60 mL). White solid (274.3 mg, 90%). Rf (light petro-
[8]
[9]
leum/ethyl acetate, 1:2) = 0.2, m.p. 154–156 °C. IR: ν = 3138, 3062,
˜
3009, 1618, 1594, 1321, 1169, 110, 1069, 1042, 1018, 986, 845, 823,
751, 679 cm–1. 1H NMR (500 MHz, CDCl3): δ = 4.36 (s, 2 H, CH2),
7.19 (ddd, J = 7.5, 4.9, 0.7 Hz, 1 H, 5Ј-H), 7.37 (d, J = 7.8 Hz, 1H
3Ј-H), 7.66 (dt, J = 7.7, 1.8 Hz, 1 H, 4Ј-H), 7.78 (d, J = 8.6 Hz, 2
H, 3ЈЈ-H, 5ЈЈ-H), 7.88 (d, J = 8.5 Hz, 2 H, 2ЈЈ-H, 6ЈЈ-H), 7.96 (s, 1
H, 5-H), 8.57 (dd, J = 4.9, 0.8 Hz, 1 H, 6Ј-H) ppm. 13C NMR
(126 MHz, CDCl3): δ = 55.8 (CH2), 121.0 (C-5), 122.6 (C-3Ј), 123.6
(C-5Ј), 123.7 (q, J = 272 Hz, CF3), 127.1 (q, J = 4 Hz, C-2ЈЈ, C-6ЈЈ,
C-3ЈЈ, C-5ЈЈ), 130.4 (q, J = 33 Hz, C-4ЈЈ), 134.0 (C-1ЈЈ), 137.5 (C-4Ј),
146.8 (C-4), 149.9 (C-6Ј), 154.1 (C-2Ј) ppm. 15N NMR (51 MHz,
CDCl3): δ = 251 (N-1), 311 (N-1Ј) ppm. 19F NMR (471 MHz,
CDCl3): δ = –62.6 (s, 3 F, CF3) ppm. HRMS (ESI+): calcd. for
[10]
[11]
C15H12F3N4 [M + H]+ 305.1014; found 305.1006. C15H11F3N4
+
(304.27): calcd. C 59.21, H 3.64, N 18.41; found C 58.99, H 3.49, N
18.21.
Supporting Information (see footnote on the first page of this article):
1
Copies of the H and 13C NMR spectra.
Acknowledgments
This work was financially supported by the Ministry of Education,
Science, and Sport, Republic of Slovenia and the Slovenian Research
Agency (grant number P1-0230; Young Researcher grant to A. B.),
and partly through the infrastructure of the EN-FIST Centre of Ex-
cellence, Ljubljana. Anja Pajer, Tina Drcˇar, and Aljosˇa Grosˇelj par-
ticipated in this study in their undergraduate projects. Their contri-
bution is gratefully acknowledged.
[12]
[13]
[14]
[15]
M. Tisˇler, Pure Appl. Chem. 1980, 52, 1611–1621.
a) T. Sasaki, K. Kanematsu, M. Murata, J. Org. Chem. 1971,
36, 446–449; b) Ch. K. Lowe-Ma, R. A. Nissan, W. S. Wilson,
J. Org. Chem. 1990, 55, 3755–3761; c) M. K. Lakshman, M. K.
Singh, D. Parrish, R. Balachandran, B. W. Day, J. Org. Chem.
2010, 75, 2461–2473; d) A. R. Ellanki, A. Islam, V. S. Rama,
R. P. Pulipati, D. Rambabu, G. R. Krishna, C. M. Reddy, K.
Mukkanti, G. R. Vanaja, A. M. Kalle, K. S. Kumar, M. Pal,
Bioorg. Med. Chem. Lett. 2012, 22, 3455–3459.
B. Chattopadhyay, C. I. Rivera Vera, S. Chuprakov, V. Gevor-
gyan, Org. Lett. 2010, 12, 2166–2169.
R. Sun, H. Wang, J. Hu, J. Zhao, H. Zhang, Org. Biomol. Chem.
2014, 12, 5954–5963.
Q. Zhang, X. Y. Wang, C. J. Cheng, R. Zhu, N. Liu, Y. F. Hu,
Org. Biomol. Chem. 2012, 10, 2847–2854.
B. R. Buckley, S. E. Dann, H. Heaney, Chem. Eur. J. 2010, 16,
6278–6284.
R. Huisgen, Angew. Chem. 1968, 80, 329–337; Angew. Chem. Int.
Ed. Engl. 1968, 7, 321–328.
a) C. Temple Jr., J. A. Montgomery, J. Org. Chem. 1965, 30,
826–829; b) D. J. Brown, P. W. Ford, J. Chem. Soc. 1967, 7, 568–
572.
S. Bräse, K. Banert, Organic Azides: Syntheses and Applications,
John Wiley & Sons, Chichester, UK, 2010.
L. P. Spencer, R. Altwer, P. Wei, L. Gelmini, J. Gauld, D. W.
Stephan, Organometallics 2003, 22, 3841–3854.
[1] M. Jurícˇek, P. H. J. Kouwer, A. E. Rowan, Chem. Commun.
2011, 47, 8740–8749.
[2] a) C. W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem. 2002,
67, 3057–3064; b) V. V. Rostovtsev, L. G. Green, V. V. Fokin,
K. B. Sharpless, Angew. Chem. Int. Ed. 2002, 41, 2596–2599; An-
gew. Chem. 2002, 114, 2708–2711.
[3] For a definition of “click” chemistry, see: H. C. Kolb, M. G.
Finn, K. B. Sharpless, Angew. Chem. Int. Ed. 2001, 40, 2004–
2021; Angew. Chem. 2001, 113, 2056–2075.
[4] J. Kosˇmrlj (Ed.), Click Triazoles, Topics in Heterocyclic Chemis-
try, vol. 28, Springer, Berlin, Heidelberg, Germany, 2012.
[5] Y. Hua, A. H. Flood, Chem. Soc. Rev. 2010, 39, 1262–1271.
[6] D. Urankar, B. Pinter, A. Pevec, F. De Proft, I. Turel, J. Kosˇmrlj,
Inorg. Chem. 2010, 49, 4820–4829.
[7] a) D. Schweinfurth, R. Pattacini, R. Strobel, B. Sarkar, Dalton
Trans. 2009, 9291–9297; b) J. K. Kilpin, J. D. Crowley, Polyhe-
dron 2010, 29, 3111–3117; c) O. Fleischel, N. Wu, A. Petitjean,
Chem. Commun. 2010, 46, 8454–8456; d) D. Urankar, A. Pevec,
I. Turel, J. Kosˇmrlj, Cryst. Growth Des. 2010, 10, 4920–4927; e)
D. Urankar, J. Kosˇmrlj, Inorg. Chim. Acta 2010, 363, 3817–3822;
f) D. Schweinfurth, S. Strobel, B. Sarkar, Inorg. Chim. Acta 2011,
374, 253–260; g) B. Pinter, A. Demsˇar, D. Urankar, F. De Proft,
J. Kosˇmrlj, Polyhedron 2011, 30, 2368–2373; h) I. Bratsos, D.
Urankar, E. Zangrando, P. Genova, J. Kosˇmrlj, E. Alessio, I.
Turel, Dalton Trans. 2011, 40, 5188–5199; i) D. Urankar, A. Pe-
vec, J. Kosˇmrlj, Eur. J. Inorg. Chem. 2011, 1921–1929; j) J. K.
Kilpin, E. L. Gavey, C. J. McAdam, C. B. Anderson, S. J. Lind,
C. C. Keep, K. C. Gordon, J. D. Crowley, Inorg. Chem. 2011, 50,
6334–6346; k) D. Schweinfurth, C.-Y. Su, S.-C. Wei, P.
Braunstein, B. Sarkar, Dalton Trans. 2012, 41, 12984–12990; l)
S.-Q. Bai, A. M. Yong, J. J. Hu, D. J. Young, X. Zhang, Y. Zong,
J. Xu, J.-L. Zuo, T. S. A. Hor, CrystEngComm 2012, 14, 961–
971; m) S. Hohloch, L. Suntrup, B. Sarkar, Organometallics
2013, 32, 7376–7385; n) M. Wolff, L. Munoz, A. François, C.
Carrayon, A. Seridi, N. Saffon, C. Picard, B. Machura, E. Beno-
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
For selected reviews, see: a) M. Meldal, C. W. Tornøe, Chem.
Rev. 2008, 108, 2952–3015; b) B. R. Buckley, H. Heaney, Mech-
anistic Investigations of Copper(I)-Catalysed Alkyne–Azide Cy-
cloaddition Reactions, in: Topics in Heterocyclic Chemistry, vol.
28 (Ed.: J. Kosˇmrlj), Springer, Berlin, Heidelberg, Germany,
2012, p. 1–30.
S. Lal, S. Díez-González, J. Org. Chem. 2011, 76, 2367–2373.
A. E. Zune, U. Hollstein, W. M. Litchman, J. Org. Chem. 1974,
39, 2461–2463, and ref. 5 therein.
[25]
[26]
[27]
a) I. V. Seregin, A. W. Schammel, V. Gevorgyan, Org. Lett. 2007,
9, 3433–3436; b) I. V. Seregin, A. W. Schammel, V. Gevorgyan,
Tetrahedron 2008, 64, 6876–6883.
14
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/KAP1
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Pages: 16
1,2,3-Triazoles Tethered to Heterocycles
[28] R. Erenler, J.-F. Biellmann, Tetrahedron Lett. 2005, 46, 5683–
[40] Recalculated to be relative to liquid NH3, from the original value
relative to neat nitromethane, by adding 380.5 ppm.
5685.
[29] B. Yan, Y. Zhou, H. Zhang, J. Chen, Y. Liu, J. Org. Chem. 2007, [41] A. R. Katritzky, C. A. Ramsden, J. A. Joule, V. V. Zhdankin,
72, 7783–7786.
Handbook of Heterocyclic Chemistry, 3rd ed., Elsevier, 2010, p.
[30] M. Wijtmans, S. Celanire, E. Snip, M. R. Gillard, E. Gelens,
P. P. Collart, B. J. Venhuis, B. Christophe, S. Hulscher, H.
van der Goot, F. Lebon, H. Timmerman, R. A. Bakker,
B. I. L. F. Lallemand, R. Leurs, P. E. Talaga, I. J. P. De Esch, J.
Med. Chem. 2008, 51, 2944–2953.
[31] R. Kleinmaier, S. Arenz, A. Karim, A.-C. C. Carlsson, M. Erdé-
lyi, Magn. Reson. Chem. 2013, 51, 46–53.
[32] L. Pazderski, Annu. Rep. NMR Spectros. 2013, 80, 33–179.
[33] R. Marek, A. Lycˇka, Curr. Org. Chem. 2002, 6, 35–66.
[34] W. Städeli, W. von Philipsborn, Org. Magn. Reson. 1981, 15,
106–109.
146.
[42] a) A. Hirschberg, P. E. Spoerri, J. Org. Chem. 1961, 26, 2356–
2360; b) E. Abushanab, A. P. Bindra, L. Goodman, H. Pe-
tersen Jr., J. Org. Chem. 1973, 38, 2049–2052.
[43] M.-L. Huber, J. T. Pinhey, J. Chem. Soc. Perkin Trans. 1 1990,
721–722.
[44] A. Nicolaides, T. Enyo, D. Miura, H. Tomioka, J. Am. Chem.
Soc. 2001, 123, 2628–2636.
[45] H. Hu, A. Zhang, L. Ding, X. Lei, L. Zhang, Molecules 2008,
13, 556–566.
[46] Q. Liu, T. Tor, Org. Lett. 2003, 5, 2571–2572.
[47] J. T. Fletcher, B. J. Bumgarner, N. D. Engels, D. A. Skoglund,
Organometallics 2008, 27, 5430–5433.
[35] A. Bax, M. F. Summers, J. Am. Chem. Soc. 1986, 108, 2093–
2094.
[36] Selected reviews: a) G. E. Martin, C. E. Hadden, J. Nat. Prod.
[48] D. Kumar, V. B. Reddy, Synthesis 2010, 1687–1691.
2000, 63, 543–585; b) G. E. Martin, A. J. Williams, Annu. Rep. [49] I. S. Park, M. S. Kwon, Y. Kim, J. S. Lee, J. Park, Org. Lett.
NMR Spectros. 2005, 55, 1–119.
2008, 10, 497–500.
[37] a) L. Stefaniak, J. D. Roberts, M. Witanowski, G. A. Webb, Org.
Magn. Reson. 1984, 22, 215–220; b) W.-Q. Fan, A. R. Katritzky,
[50] L. Jianming, L. Muwen, Y. Yuanyuan, Y. Meihuan, Z. Kelei,
Chin. J. Chem. 2012, 30, 644–650.
1,2,3-Triazoles, in: Comprehensive Heterocyclic Chemistry II, vol. [51] G.-C. Kuang, H. A. Michaels, J. T. Simmons, R. J. Clark, L.
4 (Eds.: A. R. Katritzky, C. W. Rees, E. F. V. Scriven), Elsevier,
Oxford, UK, 1996, chapter 4.01.
[38] S. Bradamante, A. Facchetti, G. A. Pagani, J. Phys. Org. Chem.
1997, 10, 514–524.
[39] C. Sakuma, M. Maeda, K. Tabei, A. Ohta, A. Kerim, T. Kurih-
ara, Magn. Reson. Chem. 1996, 34, 567–570.
Zhu, J. Org. Chem. 2010, 75, 6540–6548.
[52] G.-C. Kuang, P. M. Guha, W. S. Brotherton, J. T. Simmons,
L. A. Stankee, B. T. Nguyen, R. J. Clark, L. Zhu, J. Am. Chem.
Soc. 2011, 133, 13984–14001.
Received: August 18, 2014
Published Online: ᭿
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Date: 29-10-14 15:52:45
Pages: 16
A. Bolje, D. Urankar, J. Kosˇmrlj
FULL PAPER
Triazoles
ˇ
Isomeric 1,4-disubstituted 1,2,3-triazoles
functionalized with pyridine, pyrimidine,
and pyrazine groups were prepared by a
copper(I)-catalysed azide–alkyne cycload-
dition reaction, and analysed by 1H–15N
gs-HMBC NMR spectroscopy.
A. Bolje, D. Urankar, J. Kosmrlj* ... 1–16
Synthesis and NMR Analysis of 1,4-Disub-
stituted 1,2,3-Triazoles Tethered to Pyr-
idine, Pyrimidine, and Pyrazine Rings
Keywords: Nitrogen heterocycles / Click
chemistry / Ligand design / NMR spec-
troscopy
16
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