Catalyst-free 1,3-dipolar cycloaddition of 3-nitrochromen with sodium azide: a facile method for the synthesis of 4-aryl-1,4-dihydrochromeno[4,3-d][1,2,3]triazole derivatives

Article abstract of DOI:10.1016/j.tet.2009.05.002

1,3-Dipolar cycloaddition of 3-nitrochromen with sodium azide under catalyst-free conditions afforded 4-aryl-1,4-dihydrochromeno[4,3-d][1,2,3]triazole derivatives at 80 °C in DMSO is described. The generality of this reaction was demonstrated by synthesiz

Full text of DOI:10.1016/j.tet.2009.05.002

Tetrahedron 65 (2009) 5799–5804
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Catalyst-free 1,3-dipolar cycloaddition of 3-nitrochromen with sodium azide:
a facile method for the synthesis of 4-aryl-1,4-dihydrochromeno-
[4,3-d][1,2,3]triazole derivatives
*
Pateliya Mujjamil Habib, B. Rama Raju, Veerababurao Kavala, Chun-Wei Kuo, Ching-Fa Yao
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
1,3-Dipolar cycloaddition of 3-nitrochromen with sodium azide under catalyst-free conditions afforded
4-aryl-1,4-dihydrochromeno[4,3-d][1,2,3]triazole derivatives at 80 ꢀC in DMSO is described. The gener-
ality of this reaction was demonstrated by synthesizing an array of 4-aryl-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole derivatives. Clean reaction conditions, easy isolation, and good yields of the triazoles are
the salient features of the methodology.
Received 23 March 2009
Received in revised form 29 April 2009
Accepted 5 May 2009
Available online 8 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
efficient use of copper salts in zeolites,15 charcoal,16 polymer-sup-
ported versions,17 and nanoparticles.18 In spite of the available
Five-membered nitrogen heterocycles play an important role in
biological systems. Among these, the 1,2,3-triazole heterocycles are
reported to posses several biological activities, including anti-HIV,1
anti-allergic,2 anti-fungal,3 anti-viral,4 and anti-microbial.5 1,2,3-
Triazoles are useful building blocks in chemistry, and can be tuned
to exhibit important role in pharmacological applications due to its
stability toward light, moisture, oxygen, and metabolism in the
body.6 In addition, these moieties find wide range of applications in
industry as photosensitizers, dyes,7 agrochemicals,8 and commer-
cially employed as anti-corrosive agents.9 Owing to the importance
of these compounds, Huisgen and co-workers reported the first
synthesis of triazoles by the 1,3-dipolar cycloaddition of azide with
various alkynes.10 However, these cycloadditions were often slow
methods, some other groups also studied the [3þ2] cycloaddtion
reactions of azides with electron poor olefins and subsequent
elimination reactions.19 The synthesis of 1,2,3-triazole by 1,3-di-
polar cycloaddition of electron deficient olefins with sodium azide
in DMSO was first reported by Zefirov and co-workers in 1971.20
Later on, Zard and his co-workers revisited the reaction and studied
the optimized conditions to synthesize the NH triazoles.21 Proline
catalyzed cascade synthesis of triazoles was achieved using nitro-
olefin, aldehyde, and sodium azide.22 Similarly, the [3þ2] cyclo-
addition of TMSN3 with 3-nitrocoumarins under solvent free
conditions catalyzed by TBAF was reported.23 The scarce applica-
tion of these electron deficient substrates is probably due to the
poor reactivity of the reactant.
even at elevated temperatures and produced
a
mixture of
Apart from this, 3-nitro-2-phenyl-2H-chromen derivatives have
gained considerable attention in recent years due to its biological
and synthetic utility. Derivatives of nitrochromens served as
phospholipase C inhibitors,24 intermediates in the synthesis of
aminochromans and spiro-[N-hydroxy]-lactams,25 and 2-compo-
nents in 1,3-dipolar cycloadditions of azomethine ylides.26 Some of
the nitrochromen derivatives have been found to display efficient
optical second harmonic generation.27 Considering the synthetic
utility of 3-nitrochromens and in continuation of our research work
on nitroolefins,28 we have developed a newer route for the syn-
thesis of 4-phenyl-1,4-dihydrochromeno[4,3-d][1,2,3]triazoles by
[3þ2] cycloaddition of 3-nitro-2-phenyl-2H-chromen with sodium
azide, under catalyst-free conditions at 80 ꢀC in DMSO (Scheme 1).
Although, DMSO is an unconventional solvent, it can be employed
as an activator, a Lewis base and also as catalyst for various organic
transformations.29
regioisomers. Further, Sharpless and his co-workers utilized the
concept of click chemistry to achieve the regioselective synthesis of
1,4-disubstituted triazoles catalyzed by copper(I) with the cyclo-
addtions of terminal alkynes only.11
Recently, other reports emerged in the literature for the syn-
thesis of these molecules include the copper(I) systems in the
presence of a base,12 in aqueous PEG13 and the redox couple cop-
per(II)/ascorbic acid14 in organic or organo-aqueous systems. Het-
erogeneous catalysis conditions can also be used as illustrated by
* Corresponding author. Tel.: þ886 2 29309092; fax: þ886 2 29324249.
E-mail address: cheyaocf@ntnu.edu.tw (C.-F. Yao).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.002

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P.M. Habib et al. / Tetrahedron 65 (2009) 5799–5804
R'
nitro-2H-chromen and its derivatives under optimized reaction
conditions (Table 2).
CHO
OH
NO2
DABCO
40 °C
NO2
R
+
R"
R
R"
R'
As can be seen from Table 2, the product formation was con-
trolled by both electronic and steric factors according to the nature
of the substituent at 2-position of the nitrochromen. For example,
2-position of the nitrochromen containing the phenyl ring equip-
ped with electron-withdrawing groups such as chloro, tri-
fluromethyl, and fluoro (entries 3, 4, 5, and 7) reacted efficiently to
produce the corresponding cycloaddition products in good yields.
However, 3-nitrochromen containing the phenyl ring equipped
with electron-donating groups methyl and methoxy (entries 2, 6,
and 8) required relatively longer reaction time to give the tri-
azolochromene derivatives in moderate yields. The 3-nitro-2H-
chromen containing bulky substituents at 2-position such as
naphthyl and anthranyl (entries 10 and 11) proceeded well under
the present reaction conditions. Sterically hindered substrate such
as 2,2-dimethyl-3-nitrochromen (entry 16) required prolonged
reaction time. Whereas starting material was recovered in case of
2,2-diphenyl-3-nitrochromen (entry 17). The 3-nitrochromen
containing different functionalities at 6 and 8 positions (entries 13,
14, and 15) reacted to give the corresponding products. It is im-
portant to note that the acid-sensitive moiety such as thienyl
substituted 3-nitro-2H-chromen derivative (entry 12) survived
under the present reaction conditions. Single crystal X-ray dif-
fraction analysis for the adduct 2l showed the position of the NH
group of the triazole ring is oriented toward the benzene ring of the
3-nitrochromen. This may be due to the steric effect of the sub-
stituent present in the 2-position of the 3-nitrochromen. The X-ray
crystal structure of the cycloaddition adduct (2l) is shown in
Figure 1.
O
1a
R = OMe, Cl, Br
NaN3
80 °C, DMSO
R' = Ph, 2-OMe-Ph, 2-Cl-Ph, 2-CF3-Ph,
3-F-Ph, 4-OMe-Ph, 4-Cl-Ph, 4-Me-Ph,
3,4-methyleneoxy-Ph, 1-napthyl,
9-anthranyl, 2-thienyl, Me
N
N
HN
R" = H, Ph, Me
R
R"
R'
O
2a
58% - 82%
Scheme 1. Synthesis of 4-phenyl-1,4-dihydrochromeno[4,3-d][1,2,3]triazoles.
2. Results and discussion
The 3-nitro-2H-chromens utilized for this study were prepared
by the treatment of
b-nitroalkenes with various substituted 2-
hydroxybenzaldehydes in the presence of DABCO under solvent
free conditions reported earlier by our group.30 Initially, we in-
vestigated the reaction between 3-nitrochromen and sodium azide
at room temperature in DMSO. Unfortunately, we were not able to
isolate any of the corresponding cycloaddition products after 24 h.
At elevated temperature (40 ꢀC), we were pleased to find the
product 4-phenyl-1,4-dihydrochromeno[4,3-d][1,2,3]triazole 2a in
quantitative yield. Further, upon increasing the temperature to
80 ꢀC, the reaction was almost completed in 25 min. With this
encouraging result in hand, we carried out the optimization studies
at 80 ꢀC, varying the amounts of sodium azide.
With 1 equiv of the sodium azide as the reactant afforded the
product 2a in 63% yield after 0.5 h. By means of 2 equiv of sodium
azide, the reaction was completed to give the product in 90% yield
in 25 min. Similarly, various solvents were screened to study their
effects, including acetonitrile, 1,2-dichloroethane, water, N,N-
dimethylformamide, dimethylsulfoxide, ethanol, and 1,4-dioxane.
None of the solvent afforded the desired product, except the polar
solvent such as water, N,N-dimethylformamide, and dimethylsulf-
oxide. According to Table 1, the best yield of the cycloaddition
product was obtained with nitrochromen (1 equiv) and sodium
azide (2 equiv) in DMSO at 80 ꢀC. To further explore the scope and
limitations of this methodology, we tested various 2-substituted-3-
The most important feature of this method is bis-cycloaddi-
tion of 1,4-bis(3-nitro-2H-chromen-2-yl)benzene containing
two nitrochromene moieties. Under the present reaction condi-
tions, 1,4-bis(3-nitro-2H-chromen-2-yl)benzene was reacted
with 4 equiv of sodium azide afforded the 1,4-bis(1,4-dihydro-
chromeno[4,3-d][1,2,3]triazol-4-yl)benzene (3b) shown below
Scheme 2.
3. Conclusion
In conclusion, we have achieved a catalyst-free [3þ2] cycload-
dition of 3-nitro-2-phenyl-2H-chromen with sodium azide in
DMSO at 80 ꢀC. The procedure was compatible with structurally
diverse 3-nitro-2-substituted chromen and its derivatives. Simple
reaction conditions, catalyst-free and easy isolation of the com-
pounds make this method an alternative to the existing methods.
Table 1
4. Experimental
4.1. General
Optimization of reaction conditions
N
N
HN
NO2
solvent
80 °C
+
NaN3
CAUTION: Azides can be explosive compounds and should be
handled with great care. During our study we encountered no prob-
lems.32 Solvents for extraction and chromatography were distilled
before use. All the chemicals used were of commercial grade and
used after distillation. Analytical thin layer chromatography was
performed with E. Merck silica gel 60 F254 aluminum plates. All
purifications were carried out by flash chromatography using 230–
400 mesh silica gel. NaN3 was purchased from the Acros Organics
Co. Melting points were determined with a microscope hot-stage
apparatus and uncorrected. 1H and 13C NMR were recorded with
Varian Gemini-200 or Bruker Avance EX 400 FT NMR. Chemical
O
O
1a
2a
Entry
Solvent
Acetonitrile
1,2-Dicholoroethane
Water
N,N-Dimethylformamide
Dimethylsulfoxide
Dimethylsulfoxide
Ethanol
Yielda,b (%)
1
2
3
4
5
6c
7
8
0
0
12
38
63
90
0
1,4-Dioxane
0
shifts were reported in parts per million (d) using TMS as internal
a
Reactions were performed in 1 mmol scale.
standard, and coupling constants were expressed in hertz. MS or
HRMS were measured using a JEOL JMS-D300 or JEOL JMS-HX
110 spectrometer. All the 3-nitrochromene derivatives were
b
Yields were determined from crude 1H NMR spectra using toluene as internal
standard.
c
Sodium azide (2 equiv) was used.

P.M. Habib et al. / Tetrahedron 65 (2009) 5799–5804
5801
Table 2
Reaction of various 3-nitrochromene derivatives with sodium azide in DMSO at 80 ꢀC
Entry
3-Nitrochromen derivative
Product
Time (min)
25
Yielda,b (%)
N
HN
NO2
N
1
2a
2b
2c
2d
2e
79
O
Ph
O
N
Ph
HN
O
NO2
N
2
3
4
5
70
50
60
40
60
82
60
80
O
2-OMe-Ph
2-OMe-Ph
N
HN
NO2
N
O
2-Cl-Ph
O
2-Cl-Ph
N
HN
NO2
N
O
2-CF3-Ph
O
2-CF3-Ph
N
N
HN
NO2
O
3-F-Ph
O
3-F-Ph
N
N
HN
NO2
6
7
2f
75
35
62
74
O
4-OMe-Ph
O
4-OMe-Ph
N
N
HN
NO2
2g
O
4-Cl-Ph
O
4-Cl-Ph
N
N
HN
NO2
8
9
2h
2i
45
70
63
69
O
4-Me-Ph
O
4-Me-Ph
N
HN
O
NO2
N
3,4-methylenoxy-Ph
O
3,4-methylenoxy-Ph
N
N
HN
O
NO2
10
2j
60
64
60
O
1-napthyl
1-napthyl
N
N
HN
NO2
11
12
2k
2l
90
25
O
9-anthranyl
O
9-anthranyl
N
HN
NO2
N
77
O
2-thienyl
O
2-thienyl
(continued on next page)

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P.M. Habib et al. / Tetrahedron 65 (2009) 5799–5804
Table 2 (continued)
Entry
3-Nitrochromen derivative
Product
Time (min)
75
Yielda,b (%)
N
N
HN
O
NO2
Ph
MeO
MeO
Cl
13
14
2m
2n
61
O
Ph
N
N
HN
NO2
Ph
Cl
Br
45
50
78
70
O
O
Ph
N
N
HN
NO2
Ph
Br
15
2o
O
O
Ph
Br
Br
N
N
HN
NO2
16
17
2p
2q
180
58
O
O
O
N
N
HN
NO2
Ph
180c
Trace
Ph
Ph
Ph
O
a
Isolated yields.
Reactions were performed in 1 mmol scale.
Reaction was prolonged for 24 h.
b
c
synthesized by following known procedures and spectral data was
consistent with the literature reports.30
recrystallized. When no precipitate was observed, the triazole
was isolated after extraction with ethylacetate. Further purification
was done by column chromatography using ethylacetate/hexane as
eluent.
4.2. General procedure for the synthesis of 4-aryl-1,4-
dihydrochromeno[4,3-d][1,2,3]triazole derivatives
4.2.1. 4-Phenyl-1,4-dihydrochromeno[4,3-d][1,2,3]triazole (2a)
Colorless solid (79% yield). Mp 151–153 ꢀC. 1H NMR (CDCl3)
To the solution of the 3-nitro-2-phenyl-2H-chromen (1 mmol)
in DMSO (2 mL) was added sodium azide (2 mmol). The mixture
was then heated at 80 ꢀC until the starting material was totally
consumed as indicated by TLC (25 min to 3 h). After cooling, water
was added and the resulting precipitate was filtered, washed with
excess of water, and dried to give the desired triazole, which was
d
7.76 (d, J¼7.2 Hz, 1H), 7.45 (d, J¼6.2 Hz, 2H), 7.37–7.29 (m, 4H),
7.05–7.02 (t, J¼7.0 Hz, 2H), 6.58 (s, 1H). 13C NMR (CDCl3)
d 153.5,
141.7, 138.9, 138.2, 130.5, 128.9, 128.8, 127.2, 1233, 122.4, 117.8,
116.0, 76.3. MS (EI) m/z (%) 249 (Mþ, 100), 219 (60), 171 (50), 164
(40), 116 (10). HRMS calcd for C15H11N3O (Mþ) 249.0897, found
249.0896.
4.2.2. 4-(2-Methoxyphenyl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2b)
Colorless solid (60% yield). 1H NMR (CDCl3)
d
12.68 (s, 1H), 7.80
(d, J¼7.3 Hz, 1H), 7.33–7.22 (m, 3H), 7.06–7.00 (m, 3H), 6.96–6.89
(m, 2H), 3.85 (s, 3H). 13C NMR (CDCl3)
156.8, 153.9, 141.3, 138.5,
d
130.4, 130.3, 128.5, 127.0, 123.2, 122.2, 120.9, 117.6, 115.7, 111.3, 71.1,
55.8. MS (EI) m/z (%) 280 (Mþ, 18), 278 (100), 263 (80), 247 (15), 220
(15), 220 (15), 189 (10), 172 (10), 152 (5), 89 (10). HRMS calcd for
C16H13N3O2 (Mþ) 279.1002, found 279.1003.
4.2.3. 4-(2-Chlorophenyl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2c)
Colorless solid (82% yield). Mp 158–160 ꢀC. 1H NMR (CDCl3)
d
12.47 (s, 1H), 7.81 (d, J¼7.5 Hz, 1H), 7.47 (d, J¼7.5 Hz, 1H), 7.39 (d,
J¼7.5 Hz, 1H), 7.31–7.22 (m, 3H), 7.10–7.01 (m, 3H). 13C NMR (CDCl3)
d
153.1, 141.6, 140.1, 136.4, 133.1, 131.2, 130.6, 130.5, 130.2, 128.0,
123.1, 122.8, 117.7, 116.1, 73.9. MS (EI) m/z (%) 283 (Mþ, 20), 282
Figure 1. X-ray crystal structure of 2l (ORTEP view).31

P.M. Habib et al. / Tetrahedron 65 (2009) 5799–5804
5803
N
N
HN
NO2
80 °C
DMSO
NaN3
+
O
O
O
O
3a
O2N
N
3b
NH
N
61%
Scheme 2. Synthesis of 1,4-bis(1,4-dihydrochromeno[4,3-d][1,2,3]triazol-4-yl)benzene.
(100), 281 (25), 247 (40), 189 (15), 172 (100), 165 (10), 163 (10), 95
(5), 89 (10). HRMS calcd for C15H10ClN3O (Mþ) 283.0507, found
283.0514.
m/z (%) 264 (Mþ1, 15), 263 (Mþ 100), 248 (80), 234 (20), 220 (20),
189 (10), 172 (20), 165 (10), 130 (15), 114 (10), 8 (10). HRMS calcd for
C16H13N3O (Mþ) 263.1053, found 263.1052.
4.2.4. 4-(2-(Trifluoromethyl)phenyl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2d)
4.2.9. 4-(Benzo[d][1,3]dioxol-4-yl)-1,4-dihydrochromeno [4,3-
d][1,2,3]triazole (2i)
Colorless solid (60% yield): Mp 136–138 ꢀC. 1H NMR (CDCl3)
Colorless solid (69% yield). Mp 148–150 ꢀC. 1H NMR (CDCl3)
d
12.95 (s, 1H), 7.83 (d, J¼8.0 Hz, 1H), 7.74 (d, J¼7.8 Hz, 1H), 7.58–
d 12.2 (s, 1H), 7.78 (m, 1H), 7.29 (m, 1H), 7.29–7.27 (m, 1H), 7.08–7.02
7.50 (m, 2H), 7.47 (t, J¼7.5 Hz,1H), 7.32 (m,1H), 7.11 (t, J¼8.1 Hz,1H),
(m, 2H), 6.92 (m, 2H), 6.80 (d, J¼8.5 Hz, 1H), 5.94 (s, 2H). 13C NMR
7.04 (d, J¼8.1 Hz, 1H), 6.92 (s, 1H). 13C NMR (CDCl3)
d
153.7, 142.1,
(CDCl3) d 153.4, 148.2, 148.0, 141.9, 138.6, 132.3, 130.6, 123.2, 122.4,
139.2, 137.0, 132.6, 130.9, 130.0, 129.2, 128.7 (q, JC–F¼31.0 Hz), 126.2
(q, JC–F¼6.0 Hz), 124.3 (q, JC–F¼272.0 Hz.), 123.5, 122.9, 117.9, 116.7,
72.5 (q, JC–F¼3.0 Hz). MS (EI) m/z (%) 317 (Mþ, 70), 172 (100), 116
(10), 89 (5). HRMS calcd for C16H10 F3N3O (Mþ) 317.0770, found
317.0773.
121.3, 117.7, 115.5, 108.3, 107.8, 101.3, 76.1. MS (EI) m/z (%) 293 (Mþ,
100), 263 (25), 206 (15), 151 (10), 117 (5), 89 (5), 63 (5). HRMS calcd
for C16H11N3O3 (Mþ) 293.0798, found 293.0795.
4.2.10. 4-(Naphthalen-1-yl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2j)
4.2.5. 4-(3-Fluorophenyl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2e)
Colorless solid (64% yield). Mp 206–208 ꢀC. 1H NMR (CDCl3)
d
14.40 (s, 1H), 8.30 (d, J¼8.2 Hz, 1H), 7.89–7.80 (m, 3H), 7.58–7.49
Colorless solid (80% yield). Mp 143–145 ꢀC. 1H NMR (CDCl3)
12.40 (s, 1H), 7.79 (d, J¼7.6 Hz, 1H), 7.36–7.24 (m, 3H), 7.19 (d,
(m, 2H), 7.40–7.32 (m, 3H), 7.22–7.14 (m, 1H), 7.06 (t, J¼7.5 Hz, 1H),
d
6.95 (d, J¼8.1 Hz, 1H). 13C NMR (CDCl3)
d 153.1, 140.6, 134.5, 134.0,
J¼9.5 Hz, 1H), 7.10–6.97 (m, 3H), 6.60 (s, 1H). 13C NMR (CDCl3)
131.1, 129.8, 129.7, 128.6, 128.4, 126.4, 126.2, 125.8, 125.0, 124.2,
122.4, 122.1, 117.5, 116.3, 74.5. MS (EI) m/z (%) 299 (Mþ, 100), 270
(55), 241 (10), 172 (15), 127 (10). HRMS calcd for C19H13 N3O (Mþ)
299.1053, found 299.1061.
d
164.2 (d, JC–F¼246.0 Hz), 153.2, 141.6, 141.0 (d, JC–F¼6.0 Hz), 138.5,
130.7, 130.4 (d, JC–F¼3.0 Hz), 123.3, 122.6, 122.5 (d, JC–F¼3.0 Hz),
117.8, 115.9 (d, JC–F¼21.0 Hz), 115.4, 114.2 (d, JC–F¼23.0 Hz), 75.2. MS
(EI) m/z (%) 268 (Mþ1, 15), 267 (Mþ, 100), 237 (25), 212 (10), 190
(10), 183 (20), 172 (50), 116 (5), 89 (5). HRMS calcd for C15H10FN3O
(Mþ) 267.0802, found 267.0804.
4.2.11. 4-(Anthracen-9-yl)-1,4-dihydrochromeno [4,3-
d][1,2,3]triazole (2k)
Colorless solid (60% yield). Mp 215–217 ꢀC. 1H NMR (CDCl3)
4.2.6. 4-(4-Methoxyphenyl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2f)
d
12.04 (s, 1H), 8.53 (s, 1H), 8.21 (d, J¼8.6 Hz, 2H), 8.02 (d, J¼8.4 Hz,
2H), 7.94 (s, 1H), 7.87 (d, J¼9.5 Hz, 1H), 7.51–7.30 (m, 5H), 7.16 (t,
Colorless solid (62% yield). Mp 131–133 ꢀC. 1H NMR (CDCl3)
J¼7.5 Hz, 1H), 7.05 (d, J¼8.1 Hz, 1H). 13C NMR (CDCl3)
d 154.5, 139.4,
d
12.41 (s, 1H), 7.78 (d, J¼7.2 Hz, 1H), 7.36 (d, J¼8.6 Hz, 2H), 7.25 (m,
134.2, 131.8, 130.7, 130.3, 129.5, 127.3, 126.9, 126.5, 124.9, 124.1,
123.6, 122.7, 118.0, 116.2, 72.2. MS (EI) m/z (%) 349 (Mþ, 100), 319
(50), 304 (20), 264 (10), 178 (20). HRMS calcd for C23H15 N3O (Mþ)
349.1210, found 349.1215.
1H), 7.05 (m, 2H), 6.90 (d, J¼8.7 Hz, 2H), 6.53 (s, 1H), 3.81 (s, 3H). 13C
NMR (CDCl3)
d 160.2, 153.6, 142.1, 138.7, 130.7, 130.6, 128.9, 123.4,
122.5, 117.9, 115.7, 114.3, 76.0, 55.4. MS (EI) m/z (%) 279 (Mþ, 100),
250 (15), 248 (60), 220 (10), 190 (10), 172 (15), 152 (5), 89 (5). HRMS
calcd for C16H13N3O2 (Mþ) 279.1002, found 279.1004.
4.2.12. 4-(Thiophen-2-yl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2l)
4.2.7. 4-(4-Chlorophenyl)-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2g)
Colorless solid (77% yield). Mp 144–146 ꢀC. 1H NMR (CDCl3)
12.5 (s, 1H), 7.79 (m, 1H), 7.31 (m, 1H), 7.27 (m, 1H), 7.08–7.03 (m,
d
Colorless solid (74% yield). Mp183–185 ꢀC. 1H NMR (CDCl3)
3H), 6.96 (m, 1H), 6.84 (s, 1H). 13C NMR (MHz, CDCl3)
d
152.9, 141.8,
d
12.54 (s, 1H), 7.78 (d, J¼7.2 Hz, 1H), 7.40–7.25 (m, 5H), 7.09–7.04
138.9, 130.9, 130.7, 127.2, 127.1, 126.9, 123.4, 122.8, 118.3, 115.8, 71.8.
MS (EI) m/z (%) 255 (Mþ, 100), 225 (30), 200 (10), 171 (15), 154 (5),
127 (5). HRMS calcd for C13H9N3OS (Mþ) 255.0461, found
255.0468.
(m, 2H), 6.58 (s, 1H). 13C NMR (CDCl3)
d
152.5, 140.8, 137.9, 137.3,
133.3, 130.1, 128.8, 128.6, 122.7, 122.4, 117.5, 116.1, 74.6. MS (EI) m/z
(%) 283 (Mþ, 100), 253 (20), 247 (80), 219 (20), 172 (40), 95 (10).
HRMS calcd for C15H10ClN3O (Mþ) 283.0507, found 283.0507.
4.2.13. 8-Methoxy-4-phenyl-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2m)
4.2.8. 4-p-Tolyl-1,4-dihydrochromeno[4,3-d][1,2,3]triazole (2h)
Colorless solid (63% yield). Mp 163–165 ꢀC. 1H NMR (CDCl3)
Colorless solid (61% yield). Mp 191–193 ꢀC. 1H NMR (CDCl3)
d
12.95 (s, 1H), 7.78 (d, J¼7.3 Hz, 1H), 7.33 (d, J¼8.0 Hz, 2H), 7.28–
7.25 (m, 1H), 7.16 (d, J¼8.0 Hz, 2H), 7.06–7.02 (t, J¼8.0 Hz, 2H), 6.55
(s, 1H), 2.32 (s, 3H). 13C NMR (CDCl3)
153.5, 142.2, 138.8, 138.7,
135.7, 130.6, 129.6, 127.3, 123.4, 122.4, 117.9, 115.7, 76.2, 21.4. MS (EI)
d
7.35–7.31 (m, 5H), 7.19 (d, J¼2.9 Hz, 1H), 6.96 (d, J¼7.6 Hz, 1H),
6.81 (d, J¼3.0 Hz, 1H), 6.61 (s, 1H), 3.76 (s, 3H). 13C NMR (DMSO-d6)
d
d 154.6, 146.6, 141.1, 139.3, 130.4, 128.7, 128.1, 127.2, 118.6, 116.8,
116.0, 107.2, 75.4, 55.7. MS (EI) m/z (%) 279 (Mþ, 100), 250 (15), 224

5804
P.M. Habib et al. / Tetrahedron 65 (2009) 5799–5804
(5), 202 (30), 151 (5), 77 (3). HRMS calcd for C16H13N3O2 (Mþ)
279.1002, found 279.1006.
6. Bourne, Y.; Kolb, H. C.; Radic, Z.; Sharpless, K. B.; Taylor, P.; Marchot, P. Proc. Natl.
Acad. Sci. U.S.A. 2004, 101, 1449–1454.
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9. Morgan, N. H. (CHOMERICS) Eur. Pat. Appl. EP 437979A2 19910724, 1991.
10. (a) Huisgen, R.; Szeimies, G.; Moebius, L. Chem. Ber. 1967, 100, 2494–2507; (b)
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Chem., Int. Ed. 2002, 41, 2596–2599.
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P.; Gesson, J.-P. J. Org. Chem. 2007, 72, 3596–3599; (c) Peddibhotla, S.; Dang, Y.;
Liu, J. O.; Romo, D. J. Am. Chem. Soc. 2007, 129, 12222–12231.
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Barral, K.; Moorhouse, A. D.; Moses, J. E. Org. Lett. 2007, 9, 1809–1811.
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Lett. 2006, 8, 1689–1692; (b) Chan, T. R.; Fokin, V. V. QSAR Comb. Sci. 2007, 26,
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(b) Meek, J. S.; Fowler, J. J. Org. Chem. 1968, 33, 985–991; (c) Zefirov, M. S.;
Chapovskaya, N. K.; Kolesnikov, V. V. J. Chem. Soc., Chem. Commun. 1971, 1001–
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Ila, H.; Junjappa, H. Synthesis 1988, 453–455.
4.2.14. 8-Chloro-4-phenyl-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2n)
Colorless solid (78% yield). Mp 184–186 ꢀC. 1H NMR (CDCl3)
d
12.08 (s, 1H), 7.76 (d, J¼2.3 Hz, 1H), 7.24–7.35 (m, 5H), 7.28–7.20
(m, 1H), 7.00 (d, J¼8.8 Hz, 1H), 6.58 (s, 1H). 13C NMR (DMSO-d6)
d
152.5, 135.9, 132.6, 130.7, 130.1, 129.9, 129.6, 127.5, 122.6, 122.3,
117.1, 115.6, 73.4. MS (EI) m/z (%) 283 (Mþ, 100), 254 (70), 227 (30),
205 (30), 189 (30), 164 (10), 77 (10). HRMS calcd for C15H10ClN3O
(Mþ) 283.0507, found 283.0511.
4.2.15. 6,8-Dibromo-4-phenyl-1,4-dihydrochromeno[4,3-
d][1,2,3]triazole (2o)
Colorless solid (70% yield). Mp 203–205 ꢀC. 1H NMR (CDCl3,
DMSO-d6)
d
7.84 (d, J¼2.1 Hz, 1H), 7.60 (d, J¼2.2 Hz, 1H), 7.44 (d,
J¼7.0 Hz, 2H), 7.37–7.29 (m, 3H), 6.76 (s, 1H). 13C NMR (DMSO-d6)
d
147.4, 137.0, 133.4, 127.5, 127.4, 127.3, 126.2, 125.4, 125.3, 123.2,
122.8, 111.1, 75.5. MS (EI) m/z (%) 407 (Mþ2, 100), 378 (30), 351 (20),
296 (10), 190 (30), 162 (30), 95 (10), 77 (10). HRMS calcd for
C15H9Br2N3O (Mþ) 404.9107, found 404.9120, and for HRMS of
C15H9Br81BrN3O (Mþ) 406.9086, found 404.9084; HRMS calcd for
C15H9Br81BrN3O (Mþ) 408.9066, found 408.9075.
4.2.16. 4,4-Dimethyl-1,4-dihydrochromeno[4,3-d]-
[1,2,3]triazole (2p)
Colorless solid (58% yield). Mp 173–175 ꢀC. 1H NMR (CDCl3)
20. Zefirov, N. S.; Chapovskaya, N. K.; Kolesenikov, V. V. J. Chem. Soc., Dalton Trans.
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1493–1496.
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877; Amantini, D.; Francesco, F.; Piermatti, O.; Pizzo, F.; Zunino, E.; Vaccoro, L. J.
Org. Chem. 2005, 70, 6526–6529.
d
12.74 (s, 1H), 7.78 (d, J¼7.5 Hz, 1H,), 7.29–7.24 (m, 1H), 7.06–6.99
(m, 2H), 1.71 (s, 6H). 13C NMR (CDCl3)
d 153.2, 147.3, 130.5, 123.3,
122.1, 118.2, 115.7, 114.8, 76.9, 27.8. MS (EI) m/z (%) 201 (Mþ, 30), 186
(100), 131 (5), 103 (10), 77 (5). HRMS calcd for C11H11N3O (Mþ)
201.0897, found 201.0900.
24. Penella, F. W.; Chen, S.-F.; Behrens, D. L.; Kaltenbach, R. F.; Seitzg, S. P. J. Med.
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26. (a) Nyerges, M.; Viranyi, A.; Marth, G.; Dancso, A.; Blasko, G.; Tokea, L. Synlett
4.2.17. 1,4-Bis(1,4-dihydrochromeno[4,3-d][1,2,3]triazol-4-
yl)benzene (3b)
Colorless solid (61% yield). Mp 203–205 ꢀC. 1H NMR (DMSO-d6)
´
2004, 2761–2765; (b) Viranyi, A.; Marth, G.; Dancso, A.; Blasko, G.; Toke, L.;
d
7.67 (d, J¼6.9 Hz, 2H), 7.39 (s, 4H), 7.28 (t, J¼7.6 Hz, 2H), 7.04 (m,
Nyerges, M. Tetrahedron 2006, 62, 8720–8730.
4H), 6.76 (s, 2H). 13C NMR (DMSO-d6)
d 152.9, 141.3, 139.8, 137.6,
27. Ono, N.; Sugi, K.; Ogawaa, T.; Aramaki, S. J. Chem. Soc., Chem. Commun. 1993,
1781–1782.
130.5, 127.7, 123.0, 122.7, 117.8, 116.5, 75.4. MS (EI) m/z (%) 419 (Mþ,
100), 362 (15), 249 (20), 247 (100), 219 (10), 171 (40), 164 (15), 115
(5). HRMS calcd for C24H16N6O2 (Mþ) 420.1340, found 420.1338.
28. (a) Tu, Z.; Raju, B. R.; Liou, T.-R.; Kavala, V.; Kuo, C.-W.; Jang, Y.; Shih, Y.-H.;
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Acknowledgements
Financial support of this work by National Science Council of the
Republic of China is gratefully acknowledged.
References and notes
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