Facile construction of [6,6]-, [6,7]-, [6,8]-, and [6,9]ring-fused triazole frameworks by copper-catalyzed, tandem, one-pot, click and intramolecular arylation reactions: Elaboration to fused pentacyclic derivatives

Article abstract of DOI:10.1002/ejoc.201101816

A sequential copper-catalyzed, one-pot, click reaction-intramolecular direct arylation, which involves two mechanistically distinct reactions (atom-economical click reaction and direct arylation of 1,2,3-triazole), to generate [6,6]-, [6,7]-, [6,8]-, and

Full text of DOI:10.1002/ejoc.201101816

FULL PAPER
DOI: 10.1002/ejoc.201101816
Facile Construction of [6,6]-, [6,7]-, [6,8]-, and [6,9]Ring-Fused Triazole
Frameworks by Copper-Catalyzed, Tandem, One-Pot, Click and
Intramolecular Arylation Reactions: Elaboration to Fused Pentacyclic
Derivatives
M. Nagarjuna Reddy[a] and K. C. Kumara Swamy*[a]
Keywords: Nitrogen heterocycles / Fused-ring systems / Click reaction / Homogeneous catalysis / Copper / C–H activation /
Arylation
A sequential copper-catalyzed, one-pot, click reaction–intra-
molecular direct arylation, which involves two mechan- azide that leads to a fused pentacyclic heterocycle for the
istically distinct reactions (atom-economical click reaction former and a C–C-coupled, biphenyl-fused, tricyclic product
and direct arylation of 1,2,3-triazole), to generate [6,6]-, [6,7]-, for the latter is observed under Pd catalysis. All of the key
prepared from 2-bromobenzyl azide and 2-bromophenyl
[6,8]-, and [6,9]ring-fused triazoles is reported. Furthermore,
a unique divergence of reactivity between the fused triazoles
products have been characterized by single-crystal X-ray
crystallography.
tions,[13–15] we investigated the construction of a triazole
and a C–C bond in one pot using copper catalysis. A
number of approaches for the synthesis of 1,2,3-triazoles[8]
and benzopyrans/benzooxepines[16] are available, but com-
pounds that possess fused 1,2,3-triazole and benzopyran/
benzooxepine units are scarce.[11d,12] In this paper, we dis-
close a straightforward route to the construction of [6,6]-,
[6,7]-, [6,8]-, and [6,9]ring-fused triazole frameworks by
copper-catalyzed, tandem, one-pot click and intramolecular
arylation reactions. We also reveal an unusual divergence
of reactivity between the fused triazoles prepared from 2-
bromobenzyl azide and 2-bromophenyl azide; the former
yields a fused pentacyclic heterocycle, whereas the latter af-
fords a coupled product.
Introduction
Transition-metal-catalyzed sequential reactions and di-
rect functionalization of C–H bonds in aromatic com-
pounds have undergone rapid development in recent
years.[1,2] The former methodology permits the creation of
molecular complexity and diversity by the facile formation
of multiple covalent bonds in a one-pot transformation and
hence, minimizes the requisite reagents, separation pro-
cesses, and waste. Direct functionalization eliminates the
necessity to prefunctionalize the aryl group for cross-cou-
pling reactions and thus allows time and material economy.
Because of the relatively high cost and toxicity of palladium
catalysts used in the construction of C–C and C–N
bonds,[3,4] attention has also been paid to copper-catalyzed
reactions.[5–6] One of the most intensely investigated, rel-
evant C–N bond forming reactions is the click reaction be-
tween alkynes and organic azides that leads to 1,2,3-tri-
azoles because of the potential uses of the products, which
Results and Discussion
The precursors 1a–i and 2a–m used in this work are
shown in Scheme 1. Initially, we performed the click reac-
tion between O-propargyl iodophenol (1a) and benzyl azide
(2a) in the presence of copper(I) iodide (10 mol-%), tetra-
methylethylenediamine (TMEDA, 20 mol-%), and N,N-di-
methylformamide (DMF) at room temperature for 1 h and
then treated the resulting mixture with an excess of KOtBu
(3 equiv.) at 140 °C for 4 h to effect intramolecular aryl-
ation. This procedure afforded the fused tricyclic compound
3[11e] in 48% overall yield (Scheme 2). We then screened
various reaction parameters to identify the optimal reaction
conditions (Table 1). Although the ligands l-proline, bipyr-
idine, sarcosine, and N,NЈ-dimethylethylenediamine
(DMEDA) provided 3 in 60–64% yield (Table 1, Entries 2–
5), simple TMEDA provided a better yield (75%, Entry 6).
range from medicinal chemistry to materials science.[7–9]
A
recent report has demonstrated tandem cycloaddition and
N-arylation to synthesize triazolothiadiazepine 1,1-dioxide
derivatives.[10] Other groups have reported the transition-
metal-catalyzed arylation of 1,2,3-triazole with aryl hal-
ides.[11] As part of our ongoing research into transition-
metal-catalyzed C–C and C–N bond forming reac-
[a] School of Chemistry, University of Hyderabad,
Hyderabad-500046, A. P., India
Fax: +91-40-23012460
E-mail: kckssc@uohyd.ernet.in
kckssc@yahoo.com
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101816.
Eur. J. Org. Chem. 2012, 2013–2022
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2013

M. Nagarjuna Reddy, K. C. Kumara Swamy
FULL PAPER
Other N-substituted diamine ligands afforded only moder- Table 1. Optimization of the catalytic system for the synthesis of 3
(Scheme 2).[a]
ate yields (Entries 7–9). Keeping the catalyst loading to
5 mol-% CuI/10 mol-% TMEDA provided a lower yield
(Entry 10), whereas a higher loading (20 and 40 mol-% CuI/
TMEDA) only marginally increased the yield (77%, Entry
11). Other copper salts or KOtBu instead of LiOtBu af-
forded lower yields. Cesium carbonate failed (triazole re-
mained). LiOtBu was the best base (Entries 6–11).
Isolated yield
[%]
Entry CuX
Ligand
Base
1
2
3
4
5
6
7
8
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
TMEDA
l-Proline
Bipyridine
Sarcosine
DMEDA
TMEDA
DIPEDA
DTBEDA
DIPEA[b]
TMEDA
TMEDA
TMEDA
TMEDA
Na ascorbate
TMEDA
KOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
Cs2CO3
48
60
56
64
62
75
60
58
62
61
77
9
10[c]
11[d]
12
13
14
15
CuBr
CuCl
CuSO4
CuI
58
62
36[e]
no reaction[f]
[a] Quantities used (except for Entries 10–11): 1a (0.5 mmol), 2a
(0.5 mmol), CuX (10 mol-%), ligand (20 mol-%), base (3.0 equiv.),
DMF (1 mL). [b] DIPEA = N,N-Diisopropylethylamine. [c] CuI
(5 mol-%), TMEDA (10 mol-%). [d] CuI (20 mol-%), TMEDA
(40 mol-%). [e] Triazole 23 (41%) was recovered. [f] Triazole 23
remained as such.
Table 2. Scope of one-pot, copper-catalyzed click–intramolecular
arylation in the synthesis of 3–13.
Scheme 1. Precursors used in this work.
Scheme 2. One-pot, copper-catalyzed click reaction and direct aryl-
ation that led to 3.
With the optimized conditions in hand, the scope of this
copper-catalyzed, sequential click reaction–direct arylation
was examined by employing 1a and various benzyl and aryl
azides (Table 2). Both benzyl- (Entries 1–4) and phenyl
azides (Entries 5–9) afforded the fused chromene triazoles
(3–11) in good yields. The method was also applicable to
naphthyl- (Entry 10) and aliphatic azides (Entry 11). The
structure of 8 was confirmed by X-ray crystallography
(Supporting Information, Figure S1). To further explore the
generality and scope of this approach, reactions that used
different propargyl iodophenyl ethers 1b–e were investi-
gated for this sequential process, and the results of the syn-
thesis of 14–22 along with isolated yields are summarized
in Scheme 3. Despite being a one-pot process, the isolated
yields are good in most cases.
We also isolated the triazole intermediates 23 and 24,
which were obtained in ca. 90% yield without adding
LiOtBu. We found that for the subsequent arylation of 23, [a] Yield of the isolated product.
2014
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Facile Construction of Fused Triazoles
Scheme 4. Synthesis of 25 by the copper-catalyzed reaction of 1f
with 2a.
ous benzyl- and phenyl-substituted azides reacted readily.
Both electron-donating and -withdrawing groups, such as
methoxy, methyl, and halogens, on the azide component af-
forded decent yields of the products. Compound 31 was
characterized by X-ray crystallography (Figure S2).
Scheme 3. Structures of [6,6]ring-fused compounds 14–22.
CuI also acts as a catalyst; in its absence, only traces of 3
were obtained. Interestingly, for the latter intramolecular
arylation, CuI/PdCl2(PPh3)2 in place of CuI/LiOtBu af-
forded a lower yield (ca. 45%). As a solvent, DMF was
better than toluene; polyethylene glycol (PEG)-400 or water
worked well for the first step (click reaction) but not for the
intramolecular arylation.
Scheme 5. Copper-catalyzed, one-pot synthesis of 27–34.
We then wondered whether our methodology could be
applied to the synthesis of analogous [6,8]- and [6,9]ring-
In an effort to elaborate this method to generate a seven- fused triazoles. Substrates 1g and 1h were prepared from 2-
membered oxepin ring (in place of the six-membered pyran iodophenol, pentyn-1-ol or hexyn-1-ol following a Mitsu-
ring), 1f, prepared by a Mitsunobu reaction,[17] was treated nobu protocol. With the optimized conditions in hand, we
with 2a under the optimized reaction conditions. This reac- performed the click reaction and direct arylation on these
tion, however, led to the elimination product 25 (Scheme 4), substrates with various aryl azides to generate fused tri-
which arises from the abstraction of a proton from the CH2 azoles with large rings. For effective intramolecular aryl-
moiety connected to triazole and subsequent migration of ation, slightly longer reaction times (6–8 h) were required
the carbanion, which eliminates the iodophenoxide moiety (Scheme 6). In both cases, the starting materials were com-
(a good leaving group). Compound 25 can also be synthe- pletely consumed. The yields of the [6,8]ring-fused products
sized from TsOCH2CH2CϵCH (26) in 79% yield (TsOH 35–38 were superior to those of the [6,9] systems 39–42,
was the eliminated side product).
likely due to the possibility of formation of oligomeric/poly-
This problem was circumvented by choosing 1i as the meric entities because of intermolecular arylation. In order
substrate as it does not have a –OCH2–CH2– moiety, which to eliminate this potential side reaction, the concentration
is prone to elimination. Substrate 1i was readily synthesized of the reaction medium was changed from 0.5 to 0.25 m for
from 2-iodobenzyl alcohol and propargyl bromide in the the preparation of 39–42. However, in the stepwise route,
presence of a base. Following the experimental conditions by isolating the intermediate triazole 43, the overall yield of
above, we conducted the reaction between 1i and various 42 was 56%. We have not investigated this result further.
substituted azides, and, to our delight, fused oxepin tri- The solid-state structures of 37 (Figure S3) and 42 (Fig-
azoles 27–34 were obtained in good yields (Scheme 5). Vari- ures 1 and S4) were determined by X-ray crystallography.
Eur. J. Org. Chem. 2012, 2013–2022
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M. Nagarjuna Reddy, K. C. Kumara Swamy
FULL PAPER
and 18 relative to that of the N–CH2Ph bond in 6 and 17
plays a role in the difference in reactivity. Reactions such as
these are currently being investigated further in our labora-
tory.
Scheme 7. Palladium-catalyzed synthesis of 44–45 and 46–47.
Scheme 6. Copper-catalyzed synthesis of 35–42 and the intermedi-
ate 43.
Figure 2. Molecular structure of 44. Selected bond lengths [Å]:
N(1)–N(2) 1.326(4), N(2)–N(2) 1.3544 (19).
Conclusions
We have developed a simple method for the one-pot se-
quential, copper-catalyzed click reaction and intramolecu-
lar direct arylation of the triazoles thus formed. A new class
of heterocycles with [6,6]-, [6,7]-, [6,8]- and [6,9]ring-fused
systems has been synthesized. The generality and ready
availability of the starting materials should make this
method an attractive synthetic tool for chemists. The syn-
thesis of pentacyclic derivatives 44 and 45 and the Ullmann-
type products 46 and 47 obtained under exactly the same
Pd-catalyzed conditions has opened up new chemistry for
further exploration.
Figure 1. Molecular structure of 42 (only one of the two molecules
in the asymmetric unit is shown). N1–N2 1.361(3) and N2–N3
1.308(3) Å.
In an effort to explore the utility of the compounds thus
synthesized, we chose the ortho-substituted bromo com-
pounds 6 and 17 (benzyl derivatives) and 11 and 18 (phenyl
derivatives) for subsequent cyclization. These compounds
were subjected to palladium-catalyzed intramolecular cycli-
zation following a Fagnou protocol.[18] Precursors 6 and 17
afforded the new fused pentacyclic compounds 44 and 45
with a new seven-membered ring, whereas 11 and 18 under-
went Ullmann coupling[19] to afford 46 and 47 under the
same protocol (Scheme 7). Both are essentially clean reac-
tions, and no other products were detected. We have deter-
mined the X-ray structures of 44 and 47 (Figures 2, S5, and
Experimental Section
The general experimental conditions and synthesis of the precur-
sors are described in the Supporting Information.
(A) General Procedure for the Synthesis of Compounds 3–22 and
S6). It is possible that the rigidity of the N–Ar bond in 11 25–42: An oven-dried Schlenk tube with a magnetic stirrer bar was
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Facile Construction of Fused Triazoles
charged with CuI (10 mol-%), TMEDA (20 mol-%), and DMF
(1 mL) under a nitrogen atmosphere. O-Alkynyliodophenol 1
(0.5 mmol) and azide 2 (0.5 mmol) were added by syringe. The mix-
ture was stirred for 1 h at room temperature, and the formation of
triazole was monitored by TLC. After the complete formation of
23, lithium tert-butoxide (3.0 equiv.) was added, and the mixture
was heated at 140 °C for 4 h. The mixture was then cooled to ambi-
ent temperature, diluted with ethyl acetate (2–3 mL), passed
through a plug of celite, and washed with ethyl acetate (10–20 mL).
The filtrate was washed with water (10 mL) and brine (10 mL). The
organic layer was evaporated and the residue purified by column
chromatography on silica gel by using hexane/ethyl acetate (75:25)
as eluent to afford the desired product. Compounds 3–22 and
25–42 were obtained using the same molar quantities.
Compound 8: Yield 0.098 g (70%); m.p. 150–153 °C. IR (KBr): ν =
˜
2924, 1616, 1561, 1526, 1443, 1254, 1204, 1175, 1100, 1017, 831,
1
756 cm–1. H NMR (400 MHz, CDCl3): δ = 7.46 (d, J = 8.8 Hz, 2
H, Ar-H), 7.21 (t, J ≈ 7.8 Hz, 1 H, Ar-H), 7.08 (d, J = 8.8 Hz, 2
H, Ar-H), 7.03 (d, J = 8.0 Hz, 1 H, Ar-H), 6.89 (d, J = 8.0 Hz, 1
H, Ar-H), 6.81 (t, J = 7.6 Hz, 1 H, Ar-H), 5.53 (s, 2 H, OCH2),
3.93 (s, 3 H, OCH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.9,
153.8, 139.2, 130.7, 129.6, 128.4, 127.9, 127.1, 122.4, 118.0, 114.8,
114.0, 64.5, 55.7 ppm. LC–MS: m/z = 280 [M + 1]+. C16H13N3O2
(279.30): calcd. C 68.81, H 4.69, N 15.04; found C 68.72, H 4.61,
N 15.12. This compound was crystallized from dichloromethane/
hexane (2:1) mixture at 25 °C and its X-ray structure was deter-
mined.
Compound 9: Yield 0.093 g (71%); m.p. 82–84 °C. IR (KBr): ν =
˜
Compound 3: Yield 0.098 g (75%); m.p. 139–141 °C (ref.[11e] 143–
2919, 2853, 1613, 1520, 1443, 1343, 1219, 1198, 1148, 816, 758
1
144 °C). IR (KBr): ν = 2926, 2870, 1746, 1618, 1518, 1443, 1335,
cm–1. H NMR (400 MHz, CDCl3): δ = 7.44 (d, J ≈ 8.2 Hz, 2 H,
˜
1
1260, 1198, 1111, 1022, 768 cm–1. H NMR (400 MHz, CDCl3): δ
Ar-H), 7.38 (d, J ≈ 8.2 Hz, 2 H, Ar-H), 7.19–7.21 (m, 1 H, Ar-H),
7.03 (dd, J = 7.6 Hz, 1 H, Ar-H), 6.91 (dd, J = 7.6, 1.6 Hz, 1 H,
Ar-H), 6.78–6.82 (m, 1 H, Ar-H), 5.53 (s, 2 H, OCH2), 2.50 (s, 3
= 7.29–7.38 (m, 3 H, Ar-H), 7.18–7.23 (m, 4 H, Ar-H), 7.02 (d, J
= 8.0 Hz, 1 H, Ar-H), 6.90 (t, J = 7.6 Hz, 1 H, Ar-H), 5.82 (s, 2 H,
NCH2), 5.49 (s, 2 H, OCH2) ppm. 13C NMR (100 MHz, CDCl3): δ H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.8, 140.6,
= 153.8, 139.8, 134.7, 130.7, 129.2, 128.5, 127.8, 126.6, 122.7, 122.1,
118.0, 113.9, 64.5, 53.1 ppm. LC–MS: m/z = 264 [M + 1]+.
C16H13N3O (263.30): calcd. C 72.99, H 4.98, N 15.96; found C
73.12, H 4.93, N 16.20.
139.4, 134.3, 130.7, 130.3, 128.3, 125.5, 122.6, 121.9, 118.0, 114.0,
64.5, 21.4 ppm. LC–MS: m/z = 264 [M + 1]+. C16H13N3O (263.30):
calcd. C 72.99, H 4.98, N 15.96; found C 72.91, H 4.93, N 15.85.
Compound 10: Yield 0.114 g (69%); m.p. 153–156 °C. IR (KBr): ν
˜
Compound 4: Yield 0.111 g (65%); m.p. 134–136 °C. IR (KBr): ν =
= 3067, 2928, 1740, 1615, 1514, 1445, 1346, 1225, 1017, 828, 764
˜
1
2924, 2855, 1748, 1618, 1520, 1489, 1447, 1406, 1339, 1196, 1115,
cm–1. H NMR (400 MHz, CDCl3): δ = 7.74 (d, J ≈ 8.2 Hz, 2 H,
1
1071, 1011, 762 cm–1. H NMR (400 MHz, CDCl3): δ = 7.48 (d, J Ar-H), 7.47 (d, J ≈ 8.2 Hz, 2 H, Ar-H), 7.24 (d, J = 7.6 Hz, 1 H,
≈ 8.2 Hz, 2 H, Ar-H), 7.16–7.25 (m, 2 H, Ar-H), 7.06 (d, J ≈ 8.2 Hz,
2 H, Ar-H), 7.01 (d, J = 8.0 Hz, 1 H, Ar-H), 6.92 (m, 1 H, Ar-H),
5.76 (s, 2 H, NCH2), 5.48 (s, 2 H, OCH2) ppm. 13C NMR
Ar-H), 7.05 (d, J ≈ 7.6 Hz, 1 H, Ar-H), 6.93 (d, J = 7.6 Hz, 1 H,
Ar-H), 6.85 (t, J = 7.6 Hz, 1 H, Ar-H), 5.52 (s, 2 H, OCH2) ppm.
13C NMR (100 MHz, CDCl3): δ = 153.9, 139.8, 135.8, 133.1, 131.1,
(100 MHz, CDCl3): δ = 153.8, 139.9, 133.7, 132.4, 130.8, 128.3, 128.3, 127.2, 124.4, 122.5, 122.1, 118.2, 113.7, 64.4 ppm. LC–MS:
127.8, 122.6, 122.4, 122.2, 118.2, 113.7, 64.5, 52.5 ppm. LC–MS:
m/z = 328, 330 [M]+. C15H10BrN3O (328.17): calcd. C 54.90, H
m/z = 342, 344 [M]+. C16H12BrN3O (342.19): calcd. C 56.16, H 3.07, N 12.80; found C 54.82, H 3.15, N 12.71.
3.53, N 12.28; found C 56.32, H 3.48, N 12.15.
Compound 11: Yield 0.110 g (67%); m.p. 110–112 °C. IR (KBr): ν
˜
= 2926, 2876, 1611, 1518, 1445, 1200, 1019, 760 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.84–7.86 (m, 1 H, Ar-H), 7.53–7.58 (m, 3
H, Ar-H), 7.19–7.24 (m, 1 H, Ar-H), 7.02 (d, J = 8.4 Hz, 1 H, Ar-
Compound 5: Yield 0.099 g (66%); m.p. 100–102 °C. IR (KBr): ν =
˜
3075, 2930, 1599, 1576, 1520, 1435, 1341, 1211, 1119, 1076, 1022,
843 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.17–7.30 (m, 5 H, Ar-
H), 7.01–7.06 (m, 2 H, Ar-H), 6.93 (t, J = 8.0 Hz, 1 H, Ar-H), 5.79 H), 6.77 (t, J = 7.6 Hz, 1 H, Ar-H), 6.57 (dd, J = 7.6, 1.2 Hz, 1 H,
(s, 2 H, NCH2), 5.49 (s, 2 H, OCH2) ppm. 13C NMR (100 MHz, Ar-H), 5.61 (s, 2 H, OCH2) ppm. 13C NMR (100 MHz, CDCl3): δ
CDCl3): δ = 153.8, 139.9, 136.7, 135.3, 130.9, 130.6, 128.8, 127.9,
= 153.7, 138.3, 136.4, 134.0, 132.3, 131.0, 129.3, 128.8, 122.03,
126.8, 124.7, 122.4, 122.3, 118.2, 113.7, 64.5, 52.5 ppm. LC–MS:
122.01, 121.8, 117.8, 113.5, 64.6 ppm. LC–MS: m/z = 328, 330
m/z = 298, 300 [M]+. C16H12ClN3O (297.74): calcd. C 64.54, H [M]+. C15H10BrN3O (328.17): calcd. C 54.90, H 3.07, N 12.80;
4.06, N 14.11; found C 64.41, H 4.12, N 14.21.
found C 54.81, H 3.15, N 12.68.
Compound 6: Yield 0.110 g (64%); m.p. 120–122 °C. IR (KBr): ν =
Compound 12: Yield 0.095 g (64%); m.p. 141–144 °C. IR (KBr): ν
˜
˜
2924, 2855, 1520, 1464, 1439, 1341, 1202, 1124, 752 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.66–7.68 (m, 1 H, Ar-H), 7.20–7.24 (m, 3
H, Ar-H), 7.01–7.06 (m, 2 H, Ar-H), 6.90 (t, J = 7.6 Hz, 1 H, Ar-
H), 6.61–6.64 (m, 1 H, Ar-H), 5.89 (s, 2 H, NCH2), 5.53 (s, 2 H,
= 3059, 2922, 2861, 1618, 1559, 1508, 1447, 1385, 1200, 1017, 804,
774, 754 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.13 (m, 1 H, Ar-
H), 8.00 (d, J = 8.0 Hz, 1 H, Ar-H), 7.64–7.65 (m, 2 H, Ar-H),
7.58 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 7.48 (t, J ≈ 7.6 Hz, 1 H, Ar-H),
OCH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.7, 139.8, 134.0, 7.32 (d, J = 8.4 Hz, 1 H, Ar-H), 7.12 (t, J ≈ 7.6 Hz, 1 H, Ar-H),
133.1, 130.8, 129.9, 128.4, 128.1, 127.5, 122.4, 122.3, 121.8, 118.0,
113.6, 64.5, 53.1 ppm. LC–MS: m/z = 342, 344 [M]+. C16H12BrN3O
(342.19): calcd. C 56.16, H 3.53, N 12.28; found C 56.09, H 3.54,
N 12.41.
6.99 (d, J = 8.4 Hz, 1 H, Ar-H), 6.55 (t, J = 7.6 Hz, 1 H, Ar-H),
6.30 (dd, J = 8.0 Hz, J = 1.2 Hz, 1 H, Ar-H), 5.66 (s, 2 H, OCH2)
ppm. 13C NMR (100 MHz, CDCl3): δ = 153.7, 138.5, 134.2, 133.1,
131.2, 130.8, 129.8, 129.5, 128.4, 128.2, 127.4, 125.2, 122.4, 121.9,
117.7, 113.5, 64.7 ppm. LC–MS: m/z = 300 [M + 1]+. C19H13N3O
(299.33): calcd. C 76.24, H 4.38, N 14.04; found C 76.08, H 4.31,
N 14.15.
Compound 7: Yield 0.086 g (69%); m.p. 110–112 °C. IR (KBr): ν =
˜
3067, 2932, 2863, 1688, 1597, 1522, 1447, 1196, 1022, 980, 758
cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.55–7.61 (m, 5 H, Ar-H),
7.19–7.24 (m, 1 H, Ar-H), 7.04 (d, J = 8.0 Hz, 1 H, Ar-H), 6.89 Compound 13: Yield 0.076 g (55%); m.p. 88–90 °C. IR (KBr): ν =
˜
(dd, J = 7.6, 1.2 Hz, 1 H, Ar-H), 6.79 (m, 1 H, Ar-H), 5.53 (s, 2
H, OCH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.9, 139.5,
136.9, 130.8, 130.3, 129.8, 128.3, 125.7, 122.6, 121.9, 118.1, 113.9,
64.5 ppm. LC–MS: m/z = 250 [M + 1]+. C15H11N3O (249.27):
calcd. C 72.28, H 4.45, N 16.86; found C 72.35, H 4.41, N 16.75.
3061, 2926, 2855, 1746, 1616, 1557, 1518, 1449, 1339, 1196, 1123,
1
1024, 856, 754 cm–1. H NMR (400 MHz, CDCl3): δ = 7.35 (d, J
= 8.0 Hz, 1 H, Ar-H), 7.19–7.32 (m, 6 H, Ar-H), 6.99–7.04 (m, 2
H, Ar-H), 5.43 (s, 2 H, OCH2), 4.80 (t, J ≈ 7.8 Hz, 2 H, NCH2),
3.27 (t, J ≈ 7.8 Hz, 2 H, Ph-CH2) ppm. 13C NMR (100 MHz,
Eur. J. Org. Chem. 2012, 2013–2022
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2017

M. Nagarjuna Reddy, K. C. Kumara Swamy
FULL PAPER
CDCl3): δ = 153.7, 139.5, 136.7, 130.6, 129.0, 128.7, 127.3, 122.2,
121.9, 118.2, 114.2, 64.5, 51.0, 36.3 ppm. LC–MS: m/z = 278 [M +
1]+. C17H15N3O (277.32): calcd. C 73.63, H 5.45, N 15.15; found
C 73.55, H 5.51, N 14.98.
Compound 20: Yield 0.095 g (69%); m.p. 136–138 °C. IR (KBr): ν
˜
= 3075, 2918, 2851, 1647, 1597, 1514, 1456, 1217, 1192, 1063, 1007,
860 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.58–7.61 (m, 5 H, Ar-
H), 6.91 (s, 1 H, Ar-H), 6.53 (s, 1 H, Ar-H), 5.50 (s, 2 H, OCH2),
2.07 and 2.24 (2s, 6 H, 2 CH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 149.8, 139.9, 136.9, 133.0, 130.6, 130.2, 129.7, 128.8, 127.3,
125.7, 120.6, 113.2, 64.2, 20.7, 16.4 ppm. LC–MS: m/z = 278 [M +
1]+. C17H15N3O (277.32): calcd. C 73.63, H 5.45, N 15.15; found
C 73.45, H 5.51, N 15.07.
Compound 14: Yield 0.113 g (71%); m.p. 112–114 °C. IR (KBr): ν
˜
= 2957, 2920, 2853, 1699, 1647, 1524, 1458, 1447, 1198, 992, 729
cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.32–7.39 (m, 3 H, Ar-H),
7.19–7.23 (m, 3 H, Ar-H), 7.14 (s, 1 H, Ar-H), 6.93 (d, J = 8.4 Hz,
1 H, Ar-H), 5.85 (s, 2 H, NCH2), 5.46 (s, 2 H, OCH2), 1.16 [s, 9
H, C(CH3)3] ppm. 13C NMR (100 MHz, CDCl3): δ = 151.5, 145.0,
140.0, 134.9, 129.3, 128.5, 128.2, 127.6, 126.4, 120.0, 117.3, 113.3,
64.5, 53.3, 34.4, 31.3 ppm. LC–MS: m/z = 320 [M + 1]+.
C20H21N3O (319.41): calcd. C 75.21, H 6.63, N 13.16; found C
75.06, H 6.68, N 13.23.
Compound 21: Yield 0.111 g (71%); m.p. 118–120 °C. IR (KBr): ν
˜
= 2961, 2916, 2855, 1738, 1458, 1260, 1090, 1017, 804 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.78–7.80 (m, 3 H, Ar-H), 7.40–7.44
(m, 2 H, Ar-H), 7.24–7.26 (m, 4 H, Ar-H), 7.07–7.09 (m, 2 H, Ar-
H), 5.78 (s, 2 H, NCH2), 5.38 (s, 2 H, OCH2) ppm. 13C NMR
(100 MHz, CDCl3): δ = 154.1, 140.4, 134.9, 131.6, 129.9, 129.6,
128.9, 128.8, 128.3, 128.1, 127.2, 127.1, 124.8, 124.7, 118.7, 109.2,
64.6, 54.1 ppm. LC–MS: m/z = 314 [M + 1]+. C20H15N3O (313.36):
calcd. C 76.66, H 4.82, N 13.41; found C 76.55, H 4.85, N 13.36.
Compound 15: Yield 0.107 g (70%); m.p. 158–160 °C. IR (KBr): ν
˜
= 2961, 2926, 2855, 1699, 1524, 1456, 1262, 1208, 1101, 1030, 802
1
cm–1. H NMR (400 MHz, CDCl3): δ = 7.61 (m, 5 H, Ar-H), 7.25
(m, 1 H, Ar-H), 6.97 (d, J = 8.8 Hz, 1 H, Ar-H), 6.89 (d, J =
2.4 Hz, 1 H, Ar-H), 5.51 (s, 2 H, OCH2), 1.08 [s, 9 H, C(CH3)3]
ppm. 13C NMR (100 MHz, CDCl3): δ = 151.6, 144.8, 139.5, 137.0,
130.3, 129.7, 128.8, 127.8, 125.9, 119.6, 117.4, 113.2, 64.5, 34.2,
31.1 ppm. LC–MS: m/z = 306 [M + 1]+. C19H19N3O (305.38):
calcd. C 74.73, H 6.27, N 13.76; found C 74.85, H 6.21, N 13.64.
Compound 22: Yield 0.113 g (65%); m.p. 200–202 °C. IR (KBr): ν
˜
= 3057, 2915, 2857, 1618, 1593, 1510, 1368, 1346, 1219, 1013, 995,
812 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.93–7.97 (t, J
≈ 7.6 Hz, 2 H, Ar-H), 7.72–7.78 (m, 2 H, Ar-H), 7.21–7.61 (many
lines, 6 H, Ar-H), 7.05 (t, J ≈ 7.4 Hz, 1 H, Ar-H), 6.83 (d, J
≈ 8.8 Hz, 1 H, Ar-H), 6.50 (t, J ≈ 7.4 Hz, 1 H, Ar-H), 5.64 (d, J
≈ 12.6 Hz, 1 H, OCHaHb), 5.48 (d, J ≈ 12.6 Hz, 1 H, OCHaHb)
ppm. 13C NMR (100 MHz, CDCl3): δ = 154.2, 140.2, 134.5, 134.4,
132.0, 131.0, 130.3, 129.8, 128.7, 128.24, 128.18, 128.0, 127.7, 126.0,
125.0, 124.4, 124.2, 124.1, 122.8, 118.6, 109.1, 64.5 ppm. LC–MS:
m/z = 350 [M + 1]+. C23H15N3O (349.39): calcd. C 79.07, H 4.33,
N 12.03; found C 79.18, H 4.26, N 12.15.
Compound 16: Yield 0.099 g (67%); m.p. 119–121 °C. IR (KBr): ν
˜
= 3079, 2924, 2865, 1518, 1454, 1412, 1329, 1198, 1030, 1003, 986,
1
816, 721 cm–1. H NMR (400 MHz, CDCl3): δ = 7.31–7.40 (m, 3
H, Ar-H), 7.12–7.22 (m, 4 H, Ar-H), 6.92 (d, J = 8.8 Hz, 1 H, Ar-
H), 5.80 (s, 2 H, NCH2), 5.47 (s, 2 H, OCH2) ppm. 13C NMR
(100 MHz, CDCl3): δ = 152.1, 140.0, 134.3, 130.2, 129.3, 128.7,
127.0, 126.9, 122.7, 122.6, 119.2, 115.0, 64.6, 53.2 ppm. LC–MS:
m/z = 298 [M]+. C16H12ClN3O (297.74): calcd. C 64.54, H 4.06, N
14.11; found C 64.32, H 4.15, N 14.25.
Compound 25: This compound was synthesized according to the
general procedure described above using [(1-iodo-2-prop-2-ynyl)-
oxymethyl]benzene (1f, 0.136 g, 0.5 mmol) and benzyl azide 2a
(0.066 g, 0.5 mmol). Yield 0.075 g (82%); m.p. 36–39 °C. IR (KBr):
Compound 17: Yield 0.117 g (62%); m.p. 161–163 °C. IR (KBr): ν
˜
= 2919, 1615, 1516, 1447, 1406, 1204, 1092, 1055, 756 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.68–7.69 (m, 1 H, Ar-H), 7.21–7.24
(m, 2 H, Ar-H), 7.15 (dd, J = 8.8, 2.4 Hz, 1 H, Ar-H), 7.05–7.06
(m, 1 H, Ar-H), 6.93 (d, J = 8.8 Hz, 1 H, Ar-H), 6.68–6.70 (m, 1
H, Ar-H), 5.89 (s, 2 H, NCH2), 5.50 (s, 2 H, OCH2) ppm. 13C
NMR (100 MHz, CDCl3): δ = 152.1, 140.1, 133.6, 133.3, 130.5,
130.2, 128.4, 127.9, 127.3, 127.2, 122.3, 122.0, 119.2, 114.8, 64.7,
ν = 3117, 2922, 2859, 1736, 1636, 1537, 1495, 1456, 1225, 1051,
˜
912, 729 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.45 (s, 1 H,
triazole-H), 7.37–7.43 (m, 3 H, Ar-H), 7.27–7.29 (m, 2 H, Ar-H),
6.70 (dd, J = 11.2 Hz, J = 6.8 Hz, 1 H, CH=CH2), 5.86 (d, J =
17.6 Hz, 1 H, =CHcisHtrans), 5.52 (s, 2 H, NCH2), 5.32 (d, J =
11.2 Hz, 1 H, =CHcisHtrans) ppm. 13C NMR (100 MHz, CDCl3): δ
= 146.8, 134.6, 129.1, 128.8, 128.0, 125.6, 120.2, 116.2, 54.1 ppm.
LC–MS: m/z = 186 [M + 1]+. C11H11N3 (185.23): calcd. C 71.33,
H 5.99, N 22.69; found C 71.16, H 6.05, N 22.85.
53.0 ppm. LC–MS: m/z
=
(main peaks) 377, 379 [M]+.
C16H11BrClN3O (376.64): calcd. C 51.02, H 2.94, N 11.16; found
C 51.18, H 2.85, N 10.95.
Compound 18: Yield 0.120 g (66%); m.p. 152–154 °C. IR (KBr): ν
˜
= 3075, 2922, 1644, 1518, 1431, 1202, 1022, 984, 774 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.87–7.89 (m, 1 H, Ar-H), 7.54–7.63
(m, 3 H, Ar-H), 7.16 (dd, J = 8.4, 2.4 Hz, 1 H, Ar-H), 6.96 (d, J
≈ 8.4 Hz, 1 H, Ar-H), 6.47–6.48 (m, 1 H, Ar-H), 5.60 (d, J =
4.4 Hz, 2 H, OCH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.2,
138.7, 135.8, 134.2, 132.6, 130.7, 129.2, 129.0, 128.3, 127.0, 121.7,
Compound 27: Yield 0.112 g (81%); m.p. 133–135 °C. IR (KBr): ν
˜
= 3030, 2938, 2861, 1605, 1495, 1453, 1360, 1327, 1235, 1101, 912,
1
770, 721 cm–1. H NMR (400 MHz, CDCl3): δ = 7.33–7.42 (m, 7
H, Ar-H), 7.19 (d, J = 7.2 Hz, 2 H, Ar-H), 5.77 (s, 2 H, NCH2),
4.56 and 5.21 (2s, 4 H, 2 OCH2) ppm. 13C NMR (100 MHz,
CDCl3): δ = 145.0, 139.6, 135.7, 132.5, 129.8, 129.2, 129.0, 128.6,
128.3, 127.1, 126.5, 126.0, 70.9, 67.5, 52.6 ppm. LC–MS: m/z = 278
[M + 1]+. C17H15N3O (277.32): calcd. C 73.63, H 5.45, N 15.15;
found C 73.55, H 5.48, N 15.21.
121.6, 119.1, 114.8, 64.7 ppm. LC–MS: m/z
=
363 [M]+.
C15H9BrClN3O (362.61): calcd. C 49.69, H 2.50, N 11.59; found C
49.51, H 2.56, N 11.45.
Compound 19: Yield 0.106 g (73%); m.p. 134–137 °C. IR (KBr): ν Compound 28: Yield 0.126 g (71%); m.p. 139–141 °C. IR (KBr): ν
˜
˜
= 2963, 2917, 2866, 1516, 1435, 1329, 1198, 1015, 853, 710 cm–1.
= 3057, 2946, 2855, 1491, 1447, 1408, 1356, 1227, 1100, 1009, 916,
1H NMR (400 MHz, CDCl3): δ = 7.31–7.38 (m, 3 H, Ar-H), 7.19– 808, 774 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.50 (d, J =
7.21 (m, 2 H, Ar-H), 6.89–6.90 (m, 2 H, Ar-H), 5.81 (s, 2 H, 7.6 Hz, 2 H, Ar-H), 7.36 (m, 4 H, Ar-H), 7.07 (d, J = 7.6 Hz, 2 H,
NCH2), 5.45 (s, 2 H, OCH2), 2.17 and 2.20 (2s, 6 H, 2 CH3) ppm.
Ar-H), 5.71 (s, 2 H, NCH2), 4.56 and 5.20 (2s, 4 H, 2 OCH2) ppm.
13C NMR (100 MHz, CDCl3): δ = 149.6, 140.0, 134.9, 132.8, 130.7, 13C NMR (100 MHz, CDCl3): δ = 145.1, 139.6, 134.7, 132.3, 129.9,
129.2, 128.4, 127.2, 126.7, 120.8, 113.2, 64.3, 53.1, 20.7, 16.4 ppm.
LC–MS: m/z = 292 [M + 1]+. C18H17N3O (291.35): calcd. C 74.21,
H 5.88, N 14.42; found C 74.33, H 5.80, N 14.31.
129.1, 128.6, 128.3, 126.9, 125.8, 122.4, 70.9, 67.5, 52.1 ppm. LC–
MS: m/z = 356, 358 [M]+. C17H14BrN3O (356.22): calcd. C 57.32,
H 3.96, N 11.80; found C 57.25, H 3.91, N 11.91.
2018
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2013–2022

Facile Construction of Fused Triazoles
Compound 29: Yield 0.117 g (75%); m.p. 106–108 °C. IR (KBr): ν Compound 35: Yield 0.105 g (68%); m.p. 157–159 °C. IR (KBr): ν
˜
˜
= 2934, 2852, 1734, 1601, 1574, 1435, 1235, 1101, 912, 766 cm–1.
= 3065, 2919, 1555, 1514, 1439, 1221, 1101, 999, 826, 772 cm–1. 1H
1H NMR (400 MHz, CDCl3): δ = 7.30–7.35 (m, 6 H, Ar-H), 7.19 NMR (400 MHz, CDCl3): δ = 7.33–7.35 (m, 1 H, Ar-H), 7.19–7.25
(s, 1 H, Ar-H), 7.06 (br., 1 H, Ar-H), 5.73 (s, 2 H, NCH2), 4.56 (m, 3 H, Ar-H), 6.93–6.97 (m, 1 H, Ar-H), 6.89 (dd, J = 6.8, 2.4 Hz,
and 5.21 (2s, 4 H, 2 OCH2) ppm. 13C NMR (100 MHz, CDCl3): δ =
145.1, 139.6, 137.6, 135.2, 132.5, 130.5, 129.9, 129.1, 128.64, 128.58,
126.8, 126.7, 125.7, 124.7, 70.9, 67.5, 52.0 ppm. LC–MS: m/z = 312
[M]+. C17H14ClN3O (311.77): calcd. C 65.49, H 4.53, N 13.48;
found C 65.56, H 4.47, N 13.36.
2 H, Ar-H), 6.78 (dd, J = 7.6, 1.6 Hz, 1 H, Ar-H), 4.31 (br. s, 2 H,
OCH2), 3.83 (s, 3 H, OCH3), 3.08 (br. s, 2 H, CH2), 1.91–1.96 (m,
2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.9, 157.4,
146.0, 131.0, 130.4, 130.2, 130.0, 126.6, 124.0, 123.4, 121.9, 114.4,
76.8, 55.6, 25.4, 25.3 ppm. LC–MS: m/z = 308 [M + 1]+.
C18H17N3O2 (307.35): calcd. C 70.34, H 5.58, N 13.67; found C
70.19, H 5.49, N 13.81.
Compound 30: Yield 0.099 g (75%); m.p. 164–166 °C. IR (KBr): ν
˜
= 2928, 2845, 1593, 1501, 1451, 1235, 1113, 1090, 995, 924, 760
cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.51–7.53 (m, 3 H, Ar-H),
7.40–7.42 (m, 2 H, Ar-H), 7.28–7.36 (m, 2 H, Ar-H), 7.11 (t, J =
7.6 Hz, 1 H, Ar-H), 6.90 (d, J = 7.6 Hz, 1 H, Ar-H), 4.72 and 5.28
(2s, 4 H, 2 OCH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.9,
139.3, 137.3, 131.8, 129.8, 129.7, 129.5, 128.8, 128.3, 128.0, 126.0,
125.5, 71.5, 67.8 ppm. LC–MS: m/z = 264 [M + 1]+. C16H13N3O
(263.30): calcd. C 72.99, H 4.98, N 15.96; found C 73.12, H 4.92,
N 16.07.
Compound 36: Yield 0.096 g (66%); m.p. 176–178 °C. IR (KBr): ν
˜
= 3057, 2920, 1514, 1435, 1221, 1101, 999, 826, 772 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.32–7.36 (m, 1 H, Ar-H), 7.18–7.21 (m, 5
H, Ar-H), 6.94 (t, J = 7.6 Hz, 1 H, Ar-H), 6.76 (dd, J ≈ 7.6, 1.6 Hz,
1 H, Ar-H), 4.31 (br., 2 H, OCH2), 3.07 (br., 2 H, CH2), 2.37 (s, 3
H, CH3), 1.91–1.95 (m, 2 H, CH2) ppm. 13C NMR (100 MHz,
CDCl3): δ = 157.3, 146.0, 139.0, 134.4, 131.0, 130.3, 130.2, 129.8,
125.0, 123.9, 123.3, 121.9, 76.8, 25.4, 25.3, 21.2 ppm. LC–MS: m/z
= 292 [M + 1]+. C18H17N3O (291.35): calcd. C 74.21, H 5.88, N
14.42; found C 74.35, H 5.82, N 14.31.
Compound 31: Yield 0.112 g (77%); m.p. 160–162 °C. IR (KBr): ν
˜
= 2917, 2855, 1607, 1514, 1451, 1300, 1258, 1115, 1090, 993, 835,
765 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.25–7.34 (m, 4 H, Ar-
H), 7.12 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 6.99–7.02 (m, 2 H, Ar-H), 6.94
(d, J = 8.0 Hz, 1 H, Ar-H), 4.70 and 5.26 (2s, 4 H, 2 OCH2), 3.86
(s, 3 H, OCH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.4,
144.7, 139.3, 131.7, 130.2, 129.5, 128.6, 128.0, 127.9, 127.3, 125.6,
114.8, 71.5, 67.8, 55.6 ppm. LC–MS: m/z = 294 [M + 1]+.
C17H15N3O2 (293.32): calcd. C 69.61, H 5.15, N 14.33; found C
69.55, H 5.21, N 14.28. This compound was crystallized from a
dichloromethane/hexane (2:1) mixture at 25 °C and its X-ray struc-
ture was determined.
Compound 37: Yield 0.110 g (62%); m.p. 156–158 °C. IR (KBr): ν
˜
= 3090, 2922, 1497, 1439, 1321, 1223, 1152, 997, 843 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 8.8 Hz, 2 H, Ar-H),
7.39 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 7.20–7.27 (m, 3 H, Ar-H), 7.00 (t,
J ≈ 7.6 Hz, 1 H, Ar-H), 6.77 (d, J = 7.6 Hz, 1 H, Ar-H), 4.32 (br.,
2 H, OCH2), 3.08 (br. s, 2 H, CH2), 1.93–1.95 (m, 2 H, CH2) ppm.
13C NMR (100 MHz, CDCl3): δ = 157.4, 146.5, 135.8, 132.5, 131.4,
130.4, 130.1, 126.6, 124.2, 123.6, 122.9, 121.5, 76.9, 25.3, 25.2 ppm.
LC–MS: m/z = 356, 358 [M]+. C17H14BrN3O (356.22): calcd. C
57.32, H 3.96, N 11.80; found C 57.48, H 3.85, N 11.69. This com-
pound was crystallized from a dichloromethane/hexane (2:1) mix-
ture at 25 °C and its X-ray structure was determined.
Compound 32: Yield 0.110 g (80%); m.p. 169–171 °C. IR (KBr): ν
˜
= 2926, 2857, 1717, 1516, 1453, 1238, 1115, 1088, 995, 922, 766
cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.28–7.34 (m, 6 H, Ar-H),
7.11 (t, J = 7.6 Hz, 1 H, Ar-H), 6.93 (d, J = 8.0 Hz, 1 H, Ar-H),
4.71 and 5.26 (2s, 4 H, 2 OCH2), 2.45 (s, 3 H, CH3) ppm. 13C
NMR (100 MHz, CDCl3): δ = 144.8, 140.0, 139.2, 134.8, 131.7,
130.3, 129.5, 128.7, 128.2, 128.0, 125.8, 125.6, 71.5, 67.8, 21.4 ppm.
LC–MS: m/z = 278 [M + 1]+. C17H15N3O (277.32): calcd. C 73.63,
H 5.45, N 15.15; found C 73.55, H 5.41, N 15.27.
Compound 38: Yield 0.101 g (61%); m.p. 172–175 °C. IR (KBr): ν
˜
= 3057, 2920, 1597, 1493, 1429, 1223, 993, 770 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.96 (d, J = 8.8 Hz, 1 H, Ar-H), 7.90 (d,
J = 8.0 Hz, 1 H, Ar-H), 7.42–7.53 (m, 5 H, Ar-H), 7.19–7.23. (m,
1 H, Ar-H), 7.12–7.14 (m, 1 H, Ar-H), 6.67–6.71 (m, 1 H, Ar-H),
6.60 (dd, J = 8.0, 1.6 Hz, 1 H, Ar-H), 4.35 (br., 2 H, OCH2), 3.19
(br., 2 H, CH2), 1.98–2.03 (m, 2 H, CH2) ppm. 13C NMR
(100 MHz, CDCl3): δ = 157.1, 145.6, 134.1, 133.3, 132.5, 131.1,
130.3, 129.8, 129.0, 128.2, 127.8, 126.9, 125.5, 125.0, 123.9, 123.2,
122.7, 122.0, 77.3, 25.6, 25.2 ppm. LC–MS: m/z = 328 [M + 1]+.
C21H17N3O (327.38): calcd. C 77.04, H 5.23, N 12.83; found C
77.22, H 5.18, N 12.75.
Compound 33: Yield 0.113 g (64%); m.p. 178–180 °C. IR (KBr): ν
˜
= 2957, 2859, 1599, 1485, 1447, 1233, 1092, 1030, 916, 768 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J ≈ 8.2 Hz, 1 H, Ar-H),
7.30–7.38 (m, 3 H, Ar-H), 7.17 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 7.02 (dd,
J = 7.6 Hz, J ≈ 2.2 Hz, 1 H, Ar-H), 6.94 (d, J ≈ 8.2 Hz, 1 H, Ar-
H), 5.26 (s, 2 H, OCH2), 4.72 (s, 2 H, OCH2), 2.46 (s, 3 H, CH3)
ppm. 13C NMR (100 MHz, CDCl3): δ = 145.0, 140.1, 139.3, 136.4,
133.5, 131.7, 129.7, 128.9, 128.2, 128.1, 127.9, 126.2, 125.3, 124.6,
71.5, 67.8, 23.1 ppm. LC–MS: m/z = 356, 358 [M]+. C17H14BrN3O
(356.22): calcd. C 57.32, H 3.96, N 11.80; found C 57.25, H 3.88,
N 11.91.
Compound 39: Yield 0.075 g (46%); gummy solid. IR (neat): ν =
˜
3059, 2932, 1516, 1445, 1254, 1113, 1030, 993, 835 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.37 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 7.19–7.27
(m, 3 H, Ar-H), 6.94 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 6.82–6.86 (m, 3
H, Ar-H), 4.26 (t, J = 5.2 Hz, 2 H, OCH2), 3.79 (s, 3 H, OCH3),
2.70–2.73 (m, 2 H, CH2), 1.93–1.96 (m, 2 H, CH2), 1.80–1.84 (m,
2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.7, 157.4,
147.2, 131.7, 130.9, 130.8, 130.0, 126.0, 122.8, 121.3, 118.8, 114.2,
72.7, 55.5, 30.2, 26.7, 26.0 ppm. LC–MS: m/z = 322 [M + 1]+.
C19H19N3O2 (321.38): calcd. C 71.01, H 5.96, N 13.07; found C
71.15, H 5.88, N 13.12.
Compound 34: Yield 0.106 g (66%); m.p. 201–204 °C. IR (KBr): ν
˜
= 2978, 2868, 1595, 1512, 1458, 1285, 1252, 1086, 1063, 895, 762
cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.25–7.33 (m, 2 H, Ar-H),
7.15 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 6.93–7.01 (m, 3 H, Ar-H), 6.80 (d,
J = 8.8 Hz, 1 H, Ar-H), 5.24 (s, 2 H, OCH2), 4.69 (s, 2 H, OCH2),
4.31 (m, 4 H, OCH2CH2O) ppm. 13C NMR (100 MHz, CDCl3): δ
= 144.8, 144.6, 144.1, 139.2, 131.7, 130.5, 129.4, 128.7, 128.1, 128.0,
125.6, 119.2, 118.0, 115.4, 71.5, 67.8, 64.4, 64.3 ppm. LC–MS: m/z
Compound 40: Yield 0.065 g (43%); m.p. 100–102 °C. IR (KBr): ν
˜
= 3052, 2924, 1580, 1489, 1443, 1285, 1225, 1101, 993 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.36–7.40 (m, 1 H, Ar-H), 7.21–7.23
(m, 3 H, Ar-H), 7.13–7.15 (m, 2 H, Ar-H), 6.95 (t, J = 7.6 Hz, 1
= 322 [M + 1]+. C18H15N3O3 (321.33): calcd. C 67.28, H 4.71, N H, Ar-H), 6.83 (d, J = 7.6 Hz, 1 H, Ar-H), 4.27 (t, J ≈ 5.2 Hz, 2
13.08; found C 67.21, H 4.75, N 13.18.
H, OCH2), 2.71–2.74 (m, 2 H, CH2), 2.34 (s, 3 H, CH3), 1.94–1.95
Eur. J. Org. Chem. 2012, 2013–2022
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2019

M. Nagarjuna Reddy, K. C. Kumara Swamy
FULL PAPER
(m, 2 H, CH2), 1.82–1.84 (m, 2 H, CH2) ppm. 13C NMR 120.9, 112.9, 86.8, 63.6 ppm. LC–MS: m/z = 456, 458 [M]+.
(100 MHz, CDCl3): δ = 157.3, 147.4, 138.7, 134.3, 131.6, 130.9, C15H11BrIN3O (456.08): calcd. C 39.50, H 2.43, N 9.21; found C
130.8, 129.7, 124.4, 122.8, 121.3, 118.8, 72.6, 30.2, 26.7, 26.0, 21.2 39.41, H 2.48, N 9.32.
ppm. LC–MS: m/z = 306 [M + 1]+. C19H19N3O (305.38): calcd. C
74.73, H 6.27, N 13.76; found C 74.86, H 6.17, N 13.65.
Compound 43: This compound was synthesized following the pro-
cedure for 23. Yield 0.22 g (86%); gummy solid. IR (neat): ν =
˜
3069, 2944, 1582, 1485, 1246, 1163, 1121, 1019, 750 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.78 (s, 1 H, triazole-H), 7.74–7.77 (m, 1
H, Ar-H), 7.63–7.66 (m, 2 H, Ar-H), 7.22 (dd, J ≈ 8.4, 2.6 Hz, 1
H, Ar-H), 7.26–7.28 (m, 1 H, Ar-H), 6.78–6.80 (m, 1 H, Ar-H),
6.68–6.71 (m, 1 H, Ar-H), 4.06 (t, J ≈ 5.8 Hz, 2 H, OCH2), 2.90–
2.94 (m, 2 H, CH2), 2.48 (s, 3 H, CH3), 1.94–2.05 (m, 4 H, 2 CH2)
ppm. 13C NMR (100 MHz, CDCl3): δ = 157.4, 148.9, 139.8, 139.4,
136.3, 133.4, 129.5, 124.5, 122.5, 122.4, 119.0, 112.1, 86.7, 68.6,
28.6, 25.8, 25.3, 23.1 ppm. LC–MS: m/z = 512, 514 [M]+.
C19H19BrIN3O (512.19): calcd. C 44.56, H 3.74, N 8.20; found C
44.65, H 3.71, N 8.32.
Compound 41: Yield 0.069 g (37%); m.p. 125–127 °C. IR (KBr): ν
˜
= 3069, 2922, 1570, 1493, 1443, 1221, 992, 770 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.50 (d, J = 8.8 Hz, 2 H, Ar-H), 7.40–7.45
(m, 1 H, Ar-H), 7.28 (m, 1 H, Ar-H), 7.24 (d, J = 8.8 Hz, 2 H, Ar-
H), 6.98–7.02 (m, 1 H, Ar-H), 6.85 (dd, J = 7.6, 1.6 Hz, 1 H, Ar-
H), 4.28 (t, J = 5.2 Hz, 2 H, OCH2), 2.72–2.75 (m, 2 H, CH2),
1.81–1.99 (m, 4 H, 2 CH2) ppm. 13C NMR (100 MHz, CDCl3): δ
= 157.3, 147.8, 135.8, 132.4, 131.6, 131.2, 130.7, 125.9, 123.0, 122.6,
120.9, 119.0, 72.7, 30.2, 26.6, 26.0 ppm. LC–MS: m/z = 370, 372
[M]+. C18H16BrN3O (370.25): calcd. C 58.39, H 4.36, N 11.35;
found C 58.29, H 4.31, N 11.48.
Compound 42: Yield 0.080 g (41%); m.p. 120–122 °C. IR (KBr): ν
˜
(C) General Procedure for the Palladium-Catalyzed Coupling of 6,
11, and 17–18 Leading to 44–47: Compounds 44–47 were synthe-
sized essentially following a procedure reported by Fagnou and co-
workers.[19] Crushed K2CO3 (0.6 mmol, 2 equiv.), substrate 6, 11,
17, or 18 (0.3 mmol, 1 equiv.), Pd(OAc)2 (5 mol-% with respect to
substrate), and tricyclohexylphosphane (10 mol-%) were placed in
a 5 mL round-bottomed flask equipped with a magnetic stirrer bar.
The flask was filled with nitrogen and dimethylacetamide (1.5 mL)
was added. The reaction mixture was heated at 130 °C overnight.
After the reaction was judged complete by TLC, the mixture was
allowed to cool. The crude mixture was loaded directly onto a silica
gel column and the product was purified using an ethyl acetate/
hexanes (1:2) mixture as eluent.
= 3059, 2920, 1578, 1489, 1441, 1221, 1109, 1032, 939, 766 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.46 (d, J ≈ 8.0 Hz, 1 H, Ar-H),
7.38–7.42 (m, 1 H, Ar-H), 7.33 (m, 1 H, Ar-H), 7.22 (d, J = 8.0 Hz,
1 H, Ar-H), 6.98 (t, J = 7.6 Hz, 1 H, Ar-H), 6.92 (dd, J ≈ 8.0,
2.4 Hz, 1 H, Ar-H), 6.83–6.85 (m, 1 H, Ar-H), 4.27 (t, J = 5.2 Hz,
2 H, OCH2), 2.71–2.73 (m, 2 H, CH2), 2.36 (s, 3 H, CH3), 1.94–
1.95 (m, 2 H, CH2), 1.79–1.83 (m, 2 H, CH2) ppm. 13C NMR
(100 MHz, CDCl3): δ = 157.4, 147.7, 139.4, 135.9, 132.9, 131.6,
131.2, 130.7, 126.6, 125.0, 123.1, 123.0, 121.1, 119.0, 72.7, 30.2,
26.6, 26.0, 23.0 ppm. LC–MS: m/z = 384, 386 [M]+. C19H18BrN3O
(384.27): calcd. C 59.39, H 4.72, N 10.93; found C 59.61, H 4.64,
N 10.81. This compound was crystallized from an ethyl acetate/
hexane (2:1) mixture at 4 °C and its X-ray structure was deter-
mined.
Compound 44: Yield 0.062 g (82%); m.p. 180–182 °C. IR (KBr): ν
˜
= 2926, 2855, 1725, 1632, 1562, 1449, 1343, 1227, 1128, 1017, 764
(B) Synthesis of 23–24 and 43: Representative Procedure for 23: An
oven-dried Schlenk tube with a magnetic stirrer bar was charged
with CuI (10 mol-%), TMEDA (20 mol-%), and DMF (1 mL) un-
der a nitrogen atmosphere. (1-Iodo-2-prop-2-ynyloxy)benzene (1a,
0.5 mmol) and benzyl azide 2a (0.5 mmol) were added by syringe.
The mixture was stirred for 1 h at room temperature, diluted with
water (15 mL), and the product was extracted into ethyl acetate
(2ϫ20 mL). The organic layer was washed with brine (10 mL),
dried with sodium sulfate, and the solvent evaporated. The residue
was purified by column chromatography on silica gel by using hex-
ane/ethyl acetate (70:30) as eluent to afford 23. Yield 0.172 g (88%);
1
cm–1. H NMR (400 MHz, CDCl3): δ = 7.67 (d, J ≈ 7.6 Hz, 1 H,
Ar-H), 7.40–7.53 (m, 5 H, Ar-H), 7.09 (d, J = 7.6 Hz, 1 H, Ar-H),
5.49 (s, 2 H, NCH2), 5.47 (s, 2 H, OCH2) ppm. 13C NMR
(100 MHz, CDCl3): δ = 153.3, 138.6, 138.1, 135.3, 132.0, 131.9,
131.1, 130.8, 129.6, 129.2, 129.1, 122.3, 116.4, 112.9, 64.8, 53.6
ppm. LC–MS: m/z = 262 [M + 1]+. C16H11N3O (261.28): calcd. C
73.55, H 4.24, N 16.08; found C 73.41, H 4.19, N 16.23. This com-
pound was crystallized from an ethyl acetate/hexane (2:1) mixture
at 25 °C and its X-ray structure was determined.
Compound 45: Yield 0.068 g (79%); m.p. 220–222 °C. IR (KBr): ν
˜
= 2920, 2857, 1647, 1429, 1341, 1032, 972, 758 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.88–7.89 (m, 1 H, Ar-H), 7.55–7.57 (m, 1
H, Ar-H), 7.47–7.51 (m, 3 H, Ar-H), 7.03 (d, J = 8.8 Hz, 1 H, Ar-
H), 5.71 (d, J = 14.0 Hz, 1 H, CHAHB), 5.62 (d, J = 12.8 Hz, 1 H,
CHAHB), 5.35 (d, J = 12.8 Hz, 1 H, CHAHB), 5.17 (d, J = 14.0 Hz,
1 H, CHAHB) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.7, 137.8,
135.5, 133.8, 133.1, 133.02, 132.97, 130.4, 129.5, 128.8, 128.5, 125.8,
117.3, 115.7, 65.0, 53.3 ppm. LC–MS: m/z = 296, 298 [M]+.
C16H10ClN3O (295.73): calcd. C 64.98, H 3.41, N 14.21; found C
64.88, H 3.46, N 14.12.
m.p. 92–94 °C. IR (KBr): ν = 2917, 2361, 1564, 1474, 1454, 1437,
˜
1273, 1248, 1015, 802, 706 cm–1. 1H NMR (400 MHz, CDCl3): δ
= 7.75 (dd, J = 7.6 Hz, J = 1.2 Hz, 1 H, Ar-H), 7.64 (s, 1 H, N-
CH=C), 7.25–7.37 (m, 6 H, Ar-H), 6.97 (d, J = 8.0 Hz, 1 H, Ar-
H), 6.72 (ddǞt, J = 7.6 Hz, 1 H, Ar-H), 5.53 (s, 2 H, NCH2), 5.25
(s, 2 H, OCH2) ppm (the assignment of NCH2 /OCH2 protons is
tentative in these compounds; NCH2 protons appear to be those
upfield, on the basis of comparison to related compounds reported
here). 13C NMR (100 MHz, CDCl3): δ = 156.8, 144.5, 139.5, 134.6,
129.6, 129.2, 128.8, 128.0, 123.2, 122.9, 113.1, 86.8, 63.7, 54.3 ppm.
LC–MS: m/z = 392 [M + 1]+. C16H14IN3O (391.21): calcd. C 49.12,
H 3.61, N 10.74; found C 49.22, H 3.65, N 10.65.
Compound 46: Yield 0.06 g (80%); m.p. 241–243 °C. IR (KBr): ν =
˜
1
2922, 2865, 1616, 1516, 1439, 1213, 1152, 1003, 982, 758 cm–1. H
Compound 24: This compound was synthesized following the pro-
NMR (400 MHz, CDCl3): δ = 7.69–7.88 (m, 4 H, Ar-H), 7.46–7.50
(m, 2 H, Ar-H), 7.10–7.17 (m, 4 H, Ar-H), 6.66–6.79 (m, 4 H, Ar-
H), 6.08–6.10 (m, 2 H, Ar-H), 5.17 and 5.21 (2s, 2 H, 2 OCHAHB),
4.18 and 4.21 (2s, 2 H, 2 OCHAHB) ppm. 13C NMR (100 MHz,
CDCl3): δ = 153.4, 138.7, 135.3, 134.4, 133.9, 130.8, 130.4, 129.2,
128.0, 126.2, 122.8, 121.4, 117.5, 112.6, 64.1 ppm. LC–MS: m/z =
497 [M + 1]+. C30H20N6O2 (496.53): calcd. C 72.57, H 4.06, N
16.93; found C 72.41, H 4.12, N 17.08.
cedure for 23. Yield 0.201 g (87%); m.p. 113–115 °C. IR (KBr): ν
˜
= 3057, 2920, 2855, 1736, 1616, 1497, 1435, 1231, 1044, 822 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.15 (s, 1 H, triazole-H), 7.80
(dd, J ≈ 8.0, 1.4 Hz, 1 H, Ar-H), 7.66 (br., 4 H, Ar-H), 7.31–7.33
(m, 1 H, Ar-H), 7.02 (d, J = 8.0 Hz, 1 H, Ar-H), 6.77–6.79 (m, 1
H, Ar-H), 5.37 (s, 2 H, OCH2) ppm. 13C NMR (100 MHz, CDCl3):
δ = 156.8, 145.3, 139.7, 136.0, 133.0, 129.8, 123.5, 122.6, 122.1,
2020
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2013–2022

Facile Construction of Fused Triazoles
Compound 47: Yield 0.065 g (77%); m.p. 254–256 °C. IR (KBr): ν
˜
Acknowledgments
= 2924, 2880, 1647, 1518, 1435, 1208, 1096, 1024, 997, 824, 768
cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.70–7.92 (m, 4 H, Ar-H),
7.44–7.52 (m, 2 H, Ar-H), 6.93–7.13 (m, 4 H, Ar-H), 6.65–6.66 (m,
2 H, Ar-H), 5.87 (m, 2 H, Ar-H), 5.33 and 5.36 (2s, 2 H, 2 OCH-
AHB), 4.80 and 4.83 (2s, 2 H, 2 OCHAHB) ppm. 13C NMR
(100 MHz, CDCl3): δ = 151.8, 138.6, 134.8, 133.6, 130.5, 130.4,
129.5, 127.1, 126.7, 126.3, 121.7, 119.1, 118.7, 113.7, 64.5 ppm.
LC–MS: m/z = 565, 563 [M]+. C30H18Cl2N6O2 (565.42): calcd. C
63.73, H 3.21, N 14.86; found C 63.88, H 3.17, N 14.75. This com-
pound was crystallized from a dichloromethane/hexane (2:1) mix-
ture at 25 °C and its X-ray structure was determined.
We thank the Department of Science and Technology (DST), New
Delhi for financial support and use of the single-crystal X-ray dif-
fractometer facility and the University Grants Commission (UGC),
New Delhi for equipment under UPE and CAS programs. M. N. R.
thanks the Council of Scientific and Industrial Researc (CSIR),
New Delhi for a fellowship. K. C. K. thanks DST for a J. C. Bose
fellowship.
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Crystal Data for 8: C16H13N3O2, M = 279.29, monoclinic, space
group P21/c, a = 11.0061(11), b = 7.9658(8), c = 16.2080(16) Å, β
= 107.149(2)°, V = 1340.8(2) Å3, Z = 4, μ = 0.094 mm–1, data/
restraints/parameters: 2362/0/191,
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0.0672, wR2 (all data) = 0.0849.
Crystal Data for 31: C17H15N3O2, M = 293.32, monoclinic, space
group P21/c, a = 8.3038(17), b = 15.312(3), c = 11.271(2) Å, β =
94.644(3)°, V = 1428.4(5) Å3, Z = 4, μ = 0.092 mm–1, data/re-
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wR2 (all data) = 0.1186.
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Crystal Data for 37: C17H14BrN3O, M = 356.22, monoclinic, space
group P21/c, a = 7.6977(8), b = 13.1470(11), c = 16.0173(17) Å, β
= 97.433(9)°, V = 1607.4(3) Å3, Z = 4, μ = 2.562 mm–1, data/re-
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wR2 (all data) = 0.0959.
Crystal Data for 42: C19H18BrN3O, M = 384.27, monoclinic, space
group P21/n, a = 11.3442(10), b = 9.4867(8), c = 31.3130(3) Å, β =
90.3130(10)°, V = 3376.1(5) Å3, Z = 8, μ = 2.446 mm–1, data/re-
straints/parameters: 5902/ 0/453, R indices [IϾ2σ(I)]: R1 = 0.0371,
wR2 (all data) = 0.0946.
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¯
P1, a = 8.1536(9), b = 8.2282(8), c = 10.5769(11) Å, α =
111.598(9)°, β = 94.123(9)°, γ = 109.797(9)°, V = 604.91(11) Å3, Z
= 2, μ = 0.093 mm–1, data/restraints/parameters: 2140/ 0/181, R
indices [IϾ2σ(I)]: R1 = 0.0407, wR2 (all data) = 0.1057.
Crystal Data for 47: C30H18Cl2N6O2, M = 565.4, monoclinic, space
group C2/c, a = 9.1135(6), b = 17.2974(12), c = 16.1671(11) Å, β =
103.865(7)°, V = 2474.3(3) Å3, Z = 4, μ = 0.306 mm–1, data/re-
straints/parameters: 2186/ 0/182, R indices [IϾ2σ(I)]: R1 = 0.0397,
wR2 (all data) = 0.0979.
CCDC-832913 (for 8), -832914 (for 31), -832915 (for 37), -832916
(for 42), -832917 (for 44), and -832918 (for 47) contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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1
cle): H and 13C NMR spectra; details of the synthesis of precur-
sors 1a–e and 2a–m; ORTEP drawings.
Eur. J. Org. Chem. 2012, 2013–2022
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2021

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Received: December 17, 2011
Published Online: February 10, 2012
2022
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2013–2022