Efficient one-pot, four-component synthesis of 1,2,3-triazole-linked tetrahydrobenzo[ b[pyrans

Article abstract of DOI:10.1080/00397911.2011.602813

A one-pot procedure has been developed for the synthesis of (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene derivatives by concurrent reaction of aryloxy propargylated aldehydes, various azides, active methylene compounds, and 1,3-cyclohexanediones using catalytic amounts of Cu(OAc) ²/sodium ascorbate and diammonium hydrogen phosphate in aqueous ethanol media. Excellent conversion of starting materials was achieved to the desired (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene products.

Full text of DOI:10.1080/00397911.2011.602813

This article was downloaded by: [University Library Utrecht]
On: 09 November 2012, At: 10:36
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Efficient One-Pot, Four-Component
Synthesis of 1,2,3-Triazole-Linked
Tetrahydrobenzo[b]pyrans
David I. MaGee a , Peyman Salehi b , Minoo Dabiri c & Mahboobeh
Bahramnejad c
a Department of Chemistry, University of New Brunswick,
Fredericton, New Brunswick, Canada
b Department of Phytochemistry, Medicinal Plants and Drugs
Research Institute, Shahid Beheshti University, Tehran, Iran
c Faculty of Science, Department of Chemistry, Shahid Beheshti
University, Tehran, Iran
Accepted author version posted online: 13 Feb 2012.Version of
record first published: 08 Nov 2012.
To cite this article: David I. MaGee, Peyman Salehi, Minoo Dabiri & Mahboobeh Bahramnejad (2013):
Efficient One-Pot, Four-Component Synthesis of 1,2,3-Triazole-Linked Tetrahydrobenzo[b]pyrans,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:4, 486-497
To link to this article: http://dx.doi.org/10.1080/00397911.2011.602813
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,

demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 43: 486–497, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.602813
EFFICIENT ONE-POT, FOUR-COMPONENT
SYNTHESIS OF 1,2,3-TRIAZOLE-LINKED
TETRAHYDROBENZO[b]PYRANS
David I. MaGee,1 Peyman Salehi,2 Minoo Dabiri,3 and
Mahboobeh Bahramnejad3
1Department of Chemistry, University of New Brunswick, Fredericton,
New Brunswick, Canada
2Department of Phytochemistry, Medicinal Plants and Drugs Research
Institute, Shahid Beheshti University, Tehran, Iran
3Faculty of Science, Department of Chemistry, Shahid Beheshti University,
Tehran, Iran
GRAPHICAL ABSTRACT
Abstract A one-pot procedure has been developed for the synthesis of (1,2,3-triazolyl)
methoxyphenyl tetrahydro-5-oxo-4H-chromene derivatives by concurrent reaction of
aryloxy propargylated aldehydes, various azides, active methylene compounds, and
1,3-cyclohexanediones using catalytic amounts of Cu(OAc)2 / sodium ascorbate and dia-
mmonium hydrogen phosphate in aqueous ethanol media. Excellent conversion of starting
materials was achieved to the desired (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4-
H-chromene products.
Keywords 1,3-Dipolar cycloaddition; 4H-benzo[b]pyrans; multicomponent reaction;
1,2,3-triazoles
INTRODUCTION
‘‘Click chemistry,’’ introduced by Sharples et al., has emerged as a fast and
efficient approach for the synthesis of novel heterocyclic compounds.[1,2] Reactions
that qualify as click chemistry are modular, and wide in scope, give very good yields,
generate only innocuous by-products that can be removed by nonchromatographic
methods, are insensitive to oxygen or water, and are stereospecific.[3,4] Huisgen’s
thermal 1,3-dipolar cycloaddition of an alkyne with an azide[5] is one of the most
Received June 27, 2011.
Address correspondence to David I. MaGee, Department of Chemistry, University of New
Brunswick, P.O. Box 4400, Fredericton, NB E3B 5A3, Canada. E-mail: dmagee@unb.ca
486

1,2,3-TRIAZOLE-LINKED TETRAHYDROBENZO[b]PYRANS
487
reliable click reactions, leading to 1,2,3-triazoles, which are potential targets for drug
discovery because of their wide range of biological properties such as antibacterial,
antiviral, antiepileptic, and anti-allergenic activities.[6–8]
4H-Benzo[b]pyrans are important compounds that have received considerable
attention in recent years because of their wide range of biological activities[9] such as
anticancer, anticoagulant, diuretic, and anti-anaphylactic activities.[10] Also, they are
used as cognitive enhancers for the treatment of neurodegenerative disease, such as
Parkinson’s, Alzheimer’s, and Huntington’s diseases and Down’s syndrome as well
as for the treatment of schizophrenia and myoclonus.[11] Because of the importance
of 4H-benzo[b] pyrans, numerous methodologies have been reported for its synthesis
in recent years.[12]
The combination of a multicomponent reaction (MCR) with a classical organic
transformation has been shown to be a powerful strategy for the production of com-
plex structures in a few synthetic steps.[13] The idea of using a MCR followed by a Huis-
gen [3 þ 2] copper-catalyzed reaction was first presented by Barbas and coworkers.[14]
Recently, a number of bioactive heterocycles were synthesized via MCRs where the
click reaction was joined in separate steps, such as sequential Ugi = intermolecular
alkyne-azide cycloaddition (IAAC),[15] sequential VanLeusen = alkyne-azidecycloaddi-
tion reactions,[16] Baylis–Hillman adducts,[17] and synthesis of triazolyl-dihydropyrimi-
done derivatives under microwave irradiation combining a Biginelli reaction with
copper-catalyzed azide-alkyne cycloaddition (CuAAC).[18]
As a part of our continued interest in the development of methods for the
synthesis of heterocyclic compounds of biological importance,[19] and according to
our experience with the combination of MCRs and click chemistry,[20] we report here
a very direct method for the synthesis of tetrahydrobenzo[b]pyran-linked 1,2,3-
triazoles through a one-pot, four-component reaction.
Herein we report a new four-component reaction of oxypropargylated benzal-
dehydes 1, azides 2, active methylene compounds 3, and 1,3-cyclohexanediones 4 in
the presence of catalytic amounts of Cu(OAc)2 (10 mol%), sodium ascorbate
(20 mol%), and (NH4)2HPO4(20 mol%) in H2O = EtOH (1:1) under reflux conditions.
After stirring the mixture for 4 h, the desired products 5a–p were obtained in good
yields (Scheme 1).
Initially we examined this reaction in the presence of catalytic amounts of
Cu(OAc)2 (10 mol%) and sodium ascorbate (20 mol%) under two different conditions,
Scheme 1. Synthesis of 1,2,3-triazole-linked 4H-benzo[b]pyrans 5a–p via a one-pot, four-component
reaction.

488
D. I. MAGEE ET AL.
in the absence and presence of diammonium hydrogen phosphate. It is worth mention-
ing that in the absence of diammonium hydrogen phosphate the target compounds
were not formed at all. We also evaluated the amount of catalyst required for this
transformation. It was found that using 20 mol% of diammonium hydrogen phosphate
in aqueous ethanol was sufficient to push the reaction to completion. Increased
amounts of the catalyst did not increase the yield. Based on this finding, we investigated
the scope of this new four-component reaction and observed that this transformation
readily proceeds with a variety of oxypropargylated benzaldehydes and azides, both
of which were prepared according to known procedures.[21,22] As shown in Table 1, this
procedureworkswithawidevarietyofsubstrates. Sixdifferenttypesofazides, twotypes
of activated methylene compounds, and 1,3-cyclohexanediones were used in this reac-
tion (Scheme 1). Inspection of the results revealed that both electron-rich and
electron-deficient groups on the aromatic propargylated aldehydes can be used with
equal success. The structures of products were confirmed by physical, spectroscopic
1
[infrared (IR) H NMR, 13C NMR and mass spectra] and elemental analysis data.
The 1H NMR spectra of products 5a–p in dimethylsulfoxide (DMSO-d6) consisted of
a characteristic singlet due to the triazole proton in the region of 8.10–9.17 ppm. The
broad singlet at 6.79–6.98 ppm was assigned to the resonance of the NH2 protons. In
addition the only proton of the pyran ring appeared at 4.11–4.53 ppm.
Although the exact mechanism of this transformation is not completely clear, a
possible reaction mechanism is proposed (Scheme 2) based on these results. Initially,
Knoevenagel condensation between the aromatic aldehyde and malonitrile (or ethyl
cyanoacetate) generates intermediate 6, which then undergoes a click reaction with
azide 2 to give intermediate 7. Although we have no data to support this sequence
of reactions, it goes without saying that intermediate 7 could also be formed by revers-
ing the steps. Regardless, subsequent Michael-type addition of the cyclohexanediones
Table 1. One-pot, four-component reaction of aryl oxypropargylated aldehydes 1,
azides 2, active methylene reagents 3, and 1,3-dicarbonyl compounds 4
Activated
Yield
Product Aldehyde 1 Azide 2 methylene 3 1,3-Dicarbonyl 4 Mp (ꢀC) (%)a
5a
5b
5c
5d
5e
5f
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1c
1c
1c
1d
2a
2b
2c
2d
2f
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3a
3a
3b
3a
4a
4a
4a
4a
4a
4a
4b
4b
4a
4a
4a
4b
4a
4a
4a
4a
122–124
177–180
165–167
179–180
170–172
132–134
207–208
160–163
142–143
194–195
177–180
195–197
227–228
149–150
164–167
137–140
78
80
74
71
68
72
65
68
70
78
71
75
72
69
73
75
2a
2b
2d
2d
2a
2b
2a
2c
2e
2f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
2d
aIsolated yield based on oxypropargylated aldehydes 1.

1,2,3-TRIAZOLE-LINKED TETRAHYDROBENZO[b]PYRANS
489
Scheme 2. A plausible mechanism for the synthesis of tetrahydrobenzo[b]pyrans linked 1,2,3-triazoles.
4 to intermediate 7 would generate intermediate 8, which following base-induced
cyclization affords the corresponding products 5 (Scheme 2).
In summary, we report herein a concise method for the construction of a
1,2,3-triazole-linked 4H-benzo[b]pyran skeleton via a one-pot, four-component reac-
tion utilizing click chemistry. This protocol may have interesting implications on the
construction of structurally diverse heterocyclic molecules and will find applications
in combinatorial chemistry, diversity-oriented synthesis, and drug discovery.
EXPERIMENTAL
All starting materials were obtained from commercial sources and were used
without further purification. Oxypropargylated aldehydes 1a–d and azides 2a–f were
prepared according to reported methods.[21,22] Melting points were measured on an
Electrothermal 9100 apparatus and were not corrected. IR spectra were recorded
1
on a Fourier transform (FT)–IR 10MB BOMEM spectrometer. H and 13C NMR
spectra were recorded on a Bruker DRX-300 Avance spectrometer (300.13 and
75.47 MHz, respectively). Mass spectra were determined on a Finnigan-MAT8430
mass spectrometer operating at an ionization potential of 70 eV. Elemental analyses
were performed on an Elementar Analysensysteme GmbH Vario EL in CHNS mode.
Typical Procedure for the Synthesis of 4-(4-((1-(3-Nitrophenyl)-1H-
1,2,3-triazol-4-yl)methoxy)phenyl)-2-amino-5,6,7,8-tetrahydro-7,
7-dimethyl-5-oxo-4H-chromene-3-carbonitrile (5a)
A mixture of aromatic oxypropargylated aldehyde 1a (0.16 g, 1.0 mmol),
4-nitro-phenylazide 2a (0.16 g, 1.0 mmol), malononitrile 3a (0.66 g, 1.0 mmol), and
dimedone 4a (0.14 g, 1.0 mmol), in the presence of Cu(OAc)2 (0.02 g, 10 mol%),
sodium ascorbate (0.04 g, 20% mol), and diammonium hydrogen phosphate

490
D. I. MAGEE ET AL.
(0.026 g, 20% mol) was magnetically stirred in aqueous ethanol (H2O=EtOH, 1=1,
5 mL) under reflux conditions. After reaction completion [monitored by thin-layer
chromatography (TLC), ethyl acetate=n-hexane 1:3], ammonia and water were added
and the mixture was stirred for 30 min. Then the solid was filtered and washed with
hot ethanol to afford the pure product 5a (0.40 g, 78%) as a light yellow solid. Mp
122–124 ꢀC; IR (KBr) (tmax=cmꢁ1): 3444, 3359, 2959, 2189, 1674, 1600, 1518, 1361.
1H NMR (300.13 MHz, DMSO-d6) 0.94 (s, 3H, CH3), 1.03 (s, 3H, CH3), 2.08 (d,
1H, J ¼ 16.1 Hz, CHAHB), 2.24 (d, 1H, J ¼ 16.1 Hz, CHAHB), 2.49 (m, 2H, CH2),
4.13 (s, 1H, CH), 5.23 (s, 2H, CH2), 6.98 (br s, 2H, NH2), 6.99 (d, 2H, J ¼ 9.0 Hz,
ArH), 7.08 (d, 2H, J ¼ 8.4 Hz, ArH), 8.24 (d, 2H, J ¼ 9.0 Hz, ArH), 8.45 (d, 2H,
J ¼ 8.9 Hz, ArH), 9.15 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 27.2,
28.8, 32.2, 35.2, 50.4, 58.9, 61.4, 113.4, 114.9, 121.2, 123.7, 126.0, 128.8, 137.9,
141.3, 145.1, 147.2, 157.1, 158.9, 162.7, 196.1. LRMS, m=z (%): 512 (Mþ, 10), 372
(16), 243 (23), 175 (95), 129 (100), 64 (42). Anal. calcd. for C27H24N6O5: C, 63.27;
H, 4.72; N, 16.40. Found: C, 63.18; H, 4.80; N, 16.31.
4-(4-((1-(3-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-
amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromene-3-
carbonitrile (5b)
White solid; (0.41 g, 80%) mp 177–180 ꢀC; IR (KBr) (tmax=cmꢁ1): 3350, 3184,
2960, 2191, 1681, 1650, 1539, 1362. H NMR (300.13 MHz, DMSO-d6) 0.95 (s, 3H,
1
CH3), 1.03 (s, 3H, CH3), 2.09 (d, 1H, J ¼ 15.9 Hz, CHAHB), 2.24 (d, 1H, J ¼ 15.9 Hz,
Hz, CHAHB), 2.49 (m, 2H, CH2), 4.14 (s, 1H, CH), 5.23 (s, 2H, CH2), 6.94 (br s, 2H,
NH2), 6.99 (d, 2H, J ¼ 8.6 Hz, ArH), 7.08 (d, 2H, J ¼ 8.5 Hz, ArH), 7.90 (t, 1H,
J ¼ 8.2 Hz, ArH), 8.32 (d, 1H, J ¼ 6.0 Hz, ArH), 8.41 (d, 1H, J ¼ 9.0 Hz, ArH), 8.75
(s, 1H, ArH), 9.17 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 27.3, 28.8,
32.2, 35.2, 50.5, 58.9, 61.4, 113.4, 114.9, 115.4, 117.4, 120.2, 123.6, 123.7, 126.7,
128.7, 131.9, 137.6, 137.9, 144.9, 149.0, 153.3, 157.2, 158.9, 162.7, 196.1. LRMS,
m=z (%): 512 (Mþ, 5), 372 (10), 243 (30), 175 (98), 129 (100), 64 (45). Anal. calcd.
for C27H24N6O5: C, 63.27; H, 4.72; N, 16.40. Found: C, 62.87; H, 5.12; N, 16.08.
4-(4-((1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-
amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromene-3-
carbonitrile (5c)
White solid (0.37 g, 74%); mp 165–167 ꢀC; IR (KBr) (tmax=cmꢁ1): 3450, 3316,
2963, 2193, 1667, 1598, 1503, 1365. H NMR (300.13 MHz, DMSO-d6) 0.94 (s, 3H,
1
CH3), 1.03 (3H, s, CH3), 2.09 (d, 1H, J ¼ 15.7 Hz, CHAHB), 2.24 (d, 1H, J ¼ 15.7 Hz,
CHAHB), 2.49 (m, 2H, CH2), 4.14 (s, 1H, CH), 5.19 (s, 2H, CH2), 6.95 (br s, 2H,
NH2), 6.98 (d, 2H, J ¼ 8.4 Hz, ArH), 7.08 (d, 2H, J ¼ 8.1 Hz, ArH), 7.67 (d, 2H,
J ¼ 8.2 Hz, ArH), 7.96 (d, 2H, J ¼ 8.4 Hz, ArH), 8.95 (s, 1H, Htriazole). 13C NMR
(75.47 MHz, DMSO-d6) 27.3, 28.8, 32.2, 35.2, 50.4, 58.9, 61.5, 113.4, 114.9, 120.2,
122.3, 123.3, 128.8, 130.3, 133.5, 135.8, 137.8, 144.6, 153.8, 157.2, 158.9, 162.6,
196.1. LRMS, m=z (%): 501 (Mþ, 2), 366 (8), 273 (11), 243 (15), 164 (100), 111
(33). Anal. calcd. for C27H24ClN5O3: C, 64.60; H, 4.82; N, 13.95. Found: C,
64.51; H, 4.90; N, 13.84.

1,2,3-TRIAZOLE-LINKED TETRAHYDROBENZO[b]PYRANS
491
4-(4-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-amino-5,6,7,
8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromene-3-carbonitrile (5d)
Light yellow solid (0.34 g, 71%); mp 179–180 ꢀC; IR (KBr) (tmax=cmꢁ1): 3438,
2948, 2190, 1672, 1604, 1506, 1367. H NMR (300.13 MHz, DMSO-d6) 0.93 (s, 3H,
1
CH3), 1.01 (s, 3H, CH3), 2.10–2.25 (m, 2H, CH2), 2.49 (m, 2H, CH2), 4.11 (s, 1H,
CH), 5.08 (s, 2H, CH2), 5.59 (s, 2H, CH2), 6.98–7.33 (m, 11H, NH2 and 9ArH),
8.29 (s, 1H, Htriazole).13C NMR (75.47 MHz, DMSO-d6) 27.2, 28.7, 31.3, 32.0,
32.3, 37.1, 50.4, 53.5, 57.4, 61.9, 100.1, 111.9, 112.9, 115.2, 121.3, 128.6, 128.8,
129.3, 132.5, 136.1, 156.0, 159.3, 163.6, 196.6. LRMS, m=z (%): 481 (Mþ, 5), 357
(10), 144 (96), 91 (100), 65 (23). Anal. calcd. for C28H27N5O3: C, 69.84; H, 5.65;
N, 14.54. Found: C, 69.72; H, 5.77; N, 14.66.
4-(4-((1-(3-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-
amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromene-3-
carbonitrile (5e)
Yellow solid (0.34 g, 68%); mp 170–172 ꢀC;, IR (KBr) (tmax=cmꢁ1): 3460, 3320,
2956, 2192, 1671, 1602, 1504, 1366. H NMR (300.13 MHz, DMSO-d6) 0.94 (s, 3H,
1
CH3), 1.02 (s, 3H, CH3), 2.11–2.27 (m, 2H, CH2), 2.49 (m, 2H, CH2), 4.12 (s, 1H,
CH), 5.09 (s, 2H, CH2), 5.64 (s, 2H, CH2), 6.95–7.41 (m, 10H, NH2 and 8ArH),
8.32 (s, 1H, Htriazole).13C NMR (75.47 MHz, DMSO-d6) 27.2, 32.2, 38.4, 50.5, 52.7,
61.5, 114.5, 114.8, 115.2, 115.4, 115.5, 115.6, 124.5, 128.7, 131.3, 131.4, 132.2, 138.9,
160.9, 164.2, 191.8. LRMS, m=z (%): 499 (Mþ, 14), 163 (100), 109 (87). Anal. calcd.
for C28H26FN5O3: C, 67.32; H, 5.25; N, 14.02. Found: C, 67.19; H, 5.40; N, 13.87.
4-(2-((1-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-
amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromene-3-
carbonitrile (5f)
Yellow solid (0.37 g, 72%); mp 132–134 ꢀC; IR (KBr) (tmax=cmꢁ1): 3445, 3378,
2953, 2190, 1673, 1598, 1524, 1362. H NMR (300.13 MHz, DMSO-d6) 0.95 (s, 3H,
1
CH3), 1.00 (s, 3H, CH3), 2.08 (d, 1H, J ¼ 15.8 Hz, CHAHB), 2.22 (d, 1H, J ¼ 15.8 Hz,
CHAHB), 2.34 (m, 2H, CH2), 4.53 (s, 1H, CH), 5.21 (d, 1H, J ¼ 12.5 Hz, CHAHB),
5.33 (d, 1H, J ¼ 12.5 Hz, CHAHB), 6.79 (br s, 2H, NH2), 6.86–7.30 (m, 4H, ArH),
8.23 (d, 2H, J ¼ 8.9 Hz, ArH), 8.47 (d, 2H, J ¼ 8.9 Hz, ArH), 9.04 (s, 1H, Htriazole).
13C NMR (75.47 MHz, DMSO-d6) 27.4, 28.8, 32.2, 50.5, 57.9, 61.9, 112.4, 113.2,
115.5, 120.5, 121.2, 121.4, 123.6, 126.0, 128.3, 129.5, 133.1, 141.3, 145.2, 147.2,
155.9, 159.3, 163.4, 196.2. LRMS, m=z (%): 512 (Mþ, 5), 243 (20), 175 (95), 129
(100), 64 (47). Anal. calcd. for C27H24N6O5: C, 63.27; H, 4.72; N, 16.40. Found:
C, 63.16; H, 4.84; N, 16.27.
4-(2-((1-(3-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-
amino-5,6,7,8-tetrahydro-5-oxo-4H-chromene-3-carbonitrile (5g)
Brown solid (0.31 g, 65%); mp 207–208 ꢀC; IR (KBr) (tmax=cmꢁ1): 3472, 3371,
2889, 2195, 1683, 1657, 1589, 1531, 1356. H NMR (300.13 MHz, DMSO-d6) 1.89
1

492
D. I. MAGEE ET AL.
(m, 2H, CH2), 2.23 (m, 2H, CH2), 2.49 (m, 2H, CH2), 4.52 (s, 1H, CH), 5.22 (d, 1H,
J ¼ 12.0 Hz, CHAHB), 5.32 (d, 1H, J ¼ 12.0 Hz, CHAHB), 6.80 (br s, 2H, NH2),
6.80–7.17 (m, 4H, ArH), 7.90 (s, 1H, ArH), 8.35 (d, 2H, J ¼ 7.4 Hz, ArH), 8.72 (s,
1H, ArH), 9.11 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 20.3, 26.9,
30.9, 36.8, 57.7, 61.7, 113.1, 113.4, 115.3, 121.4, 123.7, 123.8, 126.6, 128.2, 129.4,
132.0, 133.0, 137.6, 145.0, 148.9, 155.9, 159.3, 165.4, 196.4. LRMS, m=z (%): 484
(Mþ, 2), 420 (5), 199 (20), 175 (100), 129 (92), 76 (54). Anal. calcd. for
C25H20N6O5: C, 61.98; H, 4.16; N, 17.35. Found: C, 61.89; H, 4.25; N, 17.44.
4-(2-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-amino-5,6,7,
8-tetrahydro-5-oxo-4H-chromene-3-carbonitrile (5h)
Brown solid (0.31 g, 68%); mp 160–163 ꢀC; IR (KBr) (tmax=cmꢁ1): 3443, 3350,
2933, 2191, 1679, 1657, 1493, 1531, 1212. H NMR (300.13 MHz, DMSO-d6) 1.84
1
(m, 2H, CH2), 2.18 (m, 2H, CH2), 2.38 (m, 2H, CH2), 4.46 (s, 1H, CH), 5.12 (s,
2H, CH2), 5.64 (s, 2H, CH2), 6.88 (br s, 2H, NH2), 6.99–7.35 (m, 9H, ArH), 8.32
(s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 20.2, 26.8, 36.8, 53.5, 57.3,
61.6, 112.8, 113.1, 121.3, 128.2, 128.4, 128.6, 128.7, 129.3, 132.8, 136.2, 155.9,
159.3, 165.5, 196.3. LRMS, m=z (%): 453 (Mþ, 5), 357 (10), 144 (94), 91 (100), 65
(30). Anal. calcd. for C26H23N5O3: C, 68.86; H, 5.11; N, 15.44. Found: C, 68.74;
H, 5.24; N, 15.56.
4-(2-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-amino-5,6,7,
8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromene-3-carbonitrile (5i)
Yellow solid (0.34 g, 70%); mp 142–143 ꢀC; IR (KBr) (tmax=cmꢁ1): 3504, 3365,
2959, 2191, 1682, 1648, 1455, 1369. H NMR (300.13 MHz, DMSO-d6) 0.88 (s, 3H,
1
CH3), 0.95 (s, 3H, CH3), 2.02 (d, 1H, J ¼ 15.4 Hz, CHAHB), 2.15 (d, 1H, J ¼ 15.4 Hz,
CHAHB), 2.33 (d, 1H, J ¼ 17.2 Hz, CH2), 2.49 (m, 1H, CH2), 4.45 (s, 1H, CH), 5.03
(d, 1H, J ¼ 11.6 Hz, CHAHB), 5.18 (d, 1H, J ¼ 11.6 Hz, CHAHB), 5.64 (s, 2H, CH2),
6.88–7.37 (m, 11H, NH2 and 9ArH), 8.28 (s, 1H, Htriazole). 13C NMR (75.47 MHz,
DMSO-d6) 27.2, 28.7, 31.3, 32.0, 32.3, 37.1, 50.4, 53.5, 57.4, 61.9, 100.1, 111.9,
112.9, 115.2, 121.3, 128.6, 128.8, 129.3, 132.5, 136.1, 156.0, 159.3, 163.6, 196.6.
LRMS, m=z (%): 481 (Mþ, 12), 357 (15), 144 (96), 91 (100), 65 (28). Anal. calcd.
for C28H27N5O3: C, 69.84; H, 5.65; N, 14.54. Found: C, 69.73; H, 5.76; N, 14.43.
4-(2-((1-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-
bromophenyl)-2-amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5j)
Yellow solid (0.46 g, 78%); mp 194–195 ꢀC; IR (KBr) (tmax=cmꢁ1): 3487, 3320,
3155, 2956, 2187, 1660, 1592, 1522, 1365. 1H NMR (300.13 MHz, DMSO-d6) 0.94 (s,
3H, CH3), 0.99 (s, 3H, CH3), 2.06 (d, 1H, J ¼ 15.7 Hz, CHAHB), 2.21 (d, 1H,
J ¼ 16.2 Hz, CHAHB), 2.35 (m, 2H, CH2), 4.48 (s, 1H, CH), 5.20 (d, 1H, J ¼ 12.3 Hz,
Hz, CHAHB), 5.31 (d, 1H, J ¼ 12.3 Hz, CHAHB), 6.87 (br s, 2H, NH2), 7.18 (m, 2H,
ArH), 7.36 (d, 1H, J ¼ 8.7 Hz, ArH), 8.22 (d, 2H, J ¼ 8.1 Hz, ArH), 8.46 (d, 2H,
J ¼ 7.4 Hz, ArH), 9.03 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 27.3,

1,2,3-TRIAZOLE-LINKED TETRAHYDROBENZO[b]PYRANS
493
28.8, 32.2, 50.4, 56.9, 62.0, 111.6, 112.9, 115.5, 120.3, 121.2, 123.8, 126.0, 130.9,
141.3, 144.7, 147.2, 155.3, 159.4, 163.7, 196.3. LRMS, m=z (%): 590 (Mþ, 3), 498
(13), 359 (33), 291 (46), 175 (80), 129 (100), 76 (42). Anal. calcd. for C27H23BrN6O5:
C, 54.83; H, 3.92; N, 14.21. Found: C, 54.68; H, 4.06; N, 14.36.
4-(2-((1-(3-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-
bromophenyl)-2-amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5k)
White solid (0.42 g, 71%); mp 177–180 ꢀC; IR (KBr) (tmax=cmꢁ1): 3396, 3327,
2959, 2189, 1686, 1596, 1538, 1358. H NMR (300.13 MHz, DMSO-d6) 0.96 (s, 3H,
1
CH3), 1.01 (s, 3H, CH3), 2.08 (d, 1H, J ¼ 15.9 Hz, CHAHB), 2.21 (d, 1H, J ¼ 15.9 Hz,
CHAHB), 2.38 (m, 2H, CH2), 4.48 (s, 1H, CH), 5.22 (d, 1H, J ¼ 12.4 Hz, CHAHB),
5.32 (d, 1H, J ¼ 12.4 Hz, CHAHB), 6.85 (br s, 2H, NH2), 7.18 (m, 2H, ArH), 7.36
(d, 1H, J ¼ 6.7 Hz, ArH), 7.91 (t, 1H, J ¼ 8.1 Hz, ArH), 8.37 (d, 2H, J ¼ 8.2 Hz,
ArH), 8.73 (s, 1H, ArH), 9.07 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6)
27.3, 28.8, 32.2, 50.4, 57.0, 62.1, 89.5, 111.6, 112.9, 115.4, 115.6, 123.7, 123.8,
126.7, 130.9, 131.9, 132.0, 135.2, 135.5, 137.6, 144.5, 148.9, 155.3, 159.4, 163.7,
196.3. LRMS, m=z (%): 590 (Mþ, 8), 498 (15), 359 (30), 291 (56), 175 (85), 129
(100), 76 (35). Anal. calcd. for C27H23BrN6O5: C, 54.83; H, 3.92; N, 14.21. Found:
C, 54.70; H, 4.02; N, 14.08.
Ethyl 4-(2-((1-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-
bromophenyl)-2-amino-5,6,7,8-tetrahydro-5-oxo-4H-chromene-3-
carboxylate (5l)
Light brown solid (0.46 g, 75%); mp 195–197 ꢀC; IR (KBr) (tmax =cmꢁ1): 3444,
3387, 2942, 1687, 1653, 1527, 1347. 1H NMR (300.13 MHz, DMSO-d6) 1.06 (m, 3H,
CH3), 1.84–2.35 (m, 6H, 3CH2), 3.87 (m, 2H, CH2), 4.42 (s, 1H, CH), 5.13 (s, 2H,
CH2), 7.08–7.37 (m, 3H, ArH), 7.29 (br s, 2H, NH2), 8.23–8.46 (m, 4H, ArH),
9.06 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 14.5, 20.2, 26.7, 32.9,
36.8, 59.1, 61.1, 75.5, 111.7, 113.9, 114.8, 121.2, 123.9, 124.1, 126.1, 129.9, 134.9,
135.2, 141.3, 147.2, 150.5, 156.0, 158.9, 159.9, 165.0, 166.6, 168.6, 196.7. LRMS,
m=z (%): 609 (Mþ, 10), 398 (14), 251 (22), 223 (28), 175 (100), 129 (89), 76 (36). Anal.
calcd. for C27H24BrN5O7: C, 53.13; H, 3.96; N, 11.47. Found: C, 53.00; H, 4.09; N,
11.59.
4-(2-((1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-
bromophenyl)-2-amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carbonitrile (5m)
Cream solid (0.41 g, 72%); mp 227–228 ꢀC; IR (KBr) (tmax=cmꢁ1): 3387, 3304,
3170, 2960, 2190, 1680, 1593, 1495, 1363. 1H NMR (300.13 MHz, DMSO-d6) 0.95 (s,
3H, CH3), 0.99 (s, 3H, CH3), 2.07 (d, 1H, J ¼ 15.8 Hz, CHAHB), 2.20 (d, 1H,
J ¼ 15.8 Hz, CHAHB), 2.37 (m, 2H, CH2), 4.49 (s, 1H, CH), 5.24 (m, 2H, CH2),
6.94 (br s, 2H, NH2), 7.14–7.93 (m, 7H, ArH), 8.89 (s, 1H, ArH). 13C NMR
(75.47 MHz, DMSO-d6) 27.3, 28.7, 32.2, 50.4, 56.8, 61.9, 111.6, 112.9, 115.4,

494
D. I. MAGEE ET AL.
122.4, 123.7, 130.3, 130.9, 131.7, 133.6, 135.7, 155.2, 159.4, 163.8, 196.2. LRMS, m=z
(%): 579 (Mþ, 10), 366 (8), 273 (11), 192 (54), 165 (100), 111 (35). Anal. calcd. for
C27H23BrClN5O3: C, 55.83; H, 3.99; N, 12.06. Found: C, 55.70; H, 4.11; N, 11.93.
2-Amino-4-(5-bromo-2-((1-(2-methylbenzyl)-1H-1,2,3-triazol-4-
yl)methoxy)phenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile (5n)
Dark yellow solid (0.39 g, 69%) Mp 149–150 ꢀC, IR (KBr) (tmax=cmꢁ1): 3444,
1
3331, 2956, 1674, 1483, 1366. H NMR (300.13 MHz, DMSO-d6) dH 0.86 (s, 3H,
CH3), 0.96 (s, 3H, CH3), 1.98–2.32 (m, 7H, 2CH2 and CH3), 4.38 (s, 1H, CH),
5.11 (m, 2H, CH2), 5.64 (s, 2H, CH2), 6.85 (br s, 2H, NH2), 7.14–7.32 (m, 7H,
ArH), 8.10 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 19.2, 27.2, 28.8,
32.1, 50.3, 51.5, 59.7, 62.3, 84.3, 111.4, 112.7, 115.5, 125.3, 126.7, 128.8, 129.0,
129.2, 130.9, 131.9, 134.5, 136.8, 155.5, 159.3, 163.7, 196.2. LRMS, m=z (%): 573
(Mþ, 8), 494 (17), 217 (23), 129 (84), 105 (100), 76 (45). Anal. calcd. for
C29H28BrN5O3: C, 60.63; H, 4.91; N, 12.19. Found: C, 60.47; H, 5.03; N, 12.30.
Ethyl 4-(2-((1-(3-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-
bromophenyl)-2-amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-
chromene-3-carboxylate (5o)
Cream solid (0.45 g, 73%) mp 164–167 ꢀC, IR (KBr) (tmax=cmꢁ1): 3481, 3377,
1
2967, 1688, 1655, 1533, 1368. H NMR (300.13 MHz, DMSO-d6) dH 0.73 (s, 3H,
CH3), 0.89 (s, 3H, CH3), 1.06 (t, 3H, J ¼ 6.8 Hz, CH3), 1.79 (d, 1H, J ¼ 16.8 Hz,
CHAHB), 1.89 (d, 1H, J ¼ 16.8 Hz, CHAHB), 2.15 (m, 2H, CH2), 3.86 (m, 2H,
CH2), 4.40 (s, 1H, CH), 5.13 (s, 2H, CH2), 5.69 (s, 2H, CH2), 7.01–7.44 (m, 9H,
NH2 and 7ArH), 8.17 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 14.5,
26.7, 29.2, 31.9, 32.7, 50.3, 52.6, 59.1, 61.7, 75.4, 111.6, 112.6, 114.6, 115.3, 115.6,
124.7, 124.8, 125.4, 129.9, 131.2, 131.4, 134.9, 139.1, 139.2, 142.9, 156.0, 159.8,
160.9, 163.1, 164.2, 168.6, 196.4. LRMS, m=z (%): 624 (Mþ, 10), 398 (14), 251
(22), 223 (28), 175 (100), 129 (89), 76 (36). Anal. calcd. for C30H30BrFN4O5: C,
57.61; H, 4.83; N, 8.96. Found: C, 57.45; H, 4.98; N, 8.85.
4-(2-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)-5-methylphenyl)-2-
amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4H-chromene-3-
carbonitrile (5p)
Dark yellow solid (0.37 g, 75%); mp 137–140 ꢀC; IR (KBr) (tmax=cmꢁ1): 3454,
3382, 2929, 2189, 1676, 1644, 1499, 1368. 1H NMR (300.13 MHz, DMSO-d6) 0.85 (s,
3H, CH3), 0.94 (s, 3H, CH3), 1.96–2.26 (m, 4H, 2CH2), 2.33 (s, 3H, CH3), 4.36 (s,
1H, CH), 5.02 (m, 2H, CH2), 5.61 (s, 2H, CH2), 6.77–7.48 (m, 10H, NH2 and
8ArH), 8.10 (s, 1H, Htriazole). 13C NMR (75.47 MHz, DMSO-d6) 20.2, 26.8, 36.8,
53.5, 57.3, 61.6, 112.8, 113.1, 121.3, 128.2, 128.4, 128.6, 128.7, 129.3, 132.8, 136.2,
155.8, 159.3, 165.5, 196.3. LRMS, m=z (%): 495 (Mþ, 14), 144 (85), 91 (100), 65
(42). Anal. calcd. for C29H29N5O3: C, 70.28; H, 5.90; N, 14.13. Found: C, 70.15;
H, 6.00; N, 14.24.

1,2,3-TRIAZOLE-LINKED TETRAHYDROBENZO[b]PYRANS
495
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from the Research Council of
Shahid Beheshti University and Catalyst Center of Excellence (CCE), the University
of New Brunswick, and Natural Sciences and Engineering Research Council of
Canada (NSERC).
REFERENCES
1. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click chemistry: Diverse chemical function
from a few good reactions. Angew. Chem., Int. Ed. Engl. 2001, 40, 2004–2021.
2. Kolb, H. C.; Sharpless, K. B. The growing impact of click chemistry on drug discovery.
Drug Discovery Today 2003, 8, 1128–1137.
3. Moses, J. E.; Moorhouse, A. D. The growing applications of click chemistry. Chem. Soc.
Rev. 2007, 36, 1249–1262.
4. Hein, C. D.; Liu, X.-M.; Wang, D. Click chemistry, a powerful tool for pharmaceutical
sciences. Pharm. Res. 2008, 25, 2216–2230.
5. Huisgen, R. Electrocyclic ring-opening reactions of ethylene oxides. Angew. Chem., Int.
Ed. Engl. 1977, 16, 572–585.
6. Vicentini, C. B.; Brandolini, V.; Guarneri, M.; Giori, P. Pyrazolo[3,4-d][1,2,3]triazolo-1-
carboxamides and 5-alkylaminopyrazolo[3,4-d]oxazoles: Synthesis and evaluation of the
in vitro antifungal activity. Farmaco 1992, 47, 1021–1034.
7. Fung-Tomc, J. C.; Huczko, E.; Minassian, B.; Bonner, D. P. In vitro activity of a new oral
triazole, BMS-207147 (ER-30346). Antimicrob. Agents Chemother. 1998, 42, 313–318.
8. Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn, M. R.; Emmert, D. E.; Garmon,
S. A.; Graber, D. R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer,
R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H.
Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylpheny-
l)oxazolidinones with expanded activity against the fastidious Gram-negative organisms
Haemophilus influenzae and Moraxella catarrhalis. J. Med. Chem. 2000, 43, 953–970.
9. Green, G. R.; Evans, J. M.; Vong, A. K. In Comprehensive Heterocyclic Chemistry II,
Vol. 5; A. R. Katritzky; C. W. Rees; E. F. V. Scriven (Eds.); Pergamon Press: Oxford,
1995; p. 469.
10. (a) Foye, W. O. Prinicipi di Chemico Farmaceutica; Piccin: Padova, Italy, 1991, 416; (b)
Lazzeri, A. L.; Lapi, E. On some new esters of coumarin-3-carboxylic acid with balsamic
and bronchodilator action. Bull. Chim. Farm. 1960, 99, 583–586 (c) Bonsignore, L.; Loy,
G.; Secci, D.; Calignano, A. Synthesis and pharmacological activity of 2-oxo-(2H)
1-benzopyran-3-carboxamide derivatives. Eur. J. Med. Chem. 1993, 28, 517–520.
11. Konkoy, C. S.; Fick, D. B.; Cai, S. X.; Lan, N. C.; Keana, J. F. W. PCT Int. Appl. WO.
Patent 0075123, 2000; Chem. Abstr. 2001, 134, 29313a.
12. (a) Fang, D.; Zhang, H. B.; Liu, Z. L. Synthesis of 4H-benzopyrans catalyzed by acyclic
acidic ionic liquids in aqueous media. J. Heterocycl. Chem. 2010, 47, 63–67; (b) Pore, D.
M.; Undale, K. A.; Dongare, B. B.; Desai, U. V. Potassium phosphate catalyzed a rapid
three-component synthesis of tetrahydrobenzo[b]pyran at ambient temperature. Catal.
Lett. 2009, 132, 104–108; (c) Yu, L. Q.; Liu, F.; You, Q. D. One-pot synthesis of tetrahy-
drobenzo[b]pyran derivatives catalyzed by amines in aqueous media. Org. Prep. Proced.
Int. 2009, 41, 77–82; (d) Sabitha, G.; Arundhathi, K.; Sudhakar, K.; Sastry, B. S.; Yadav,
J. S. Cerium(III) chloride–catalyzed one-pot synthesis of tetrahydrobenzo[b] pyrans.
Synth. Commun. 2009, 39, 433–442; (e) Hekmatshoar, R.; Mojedi, S.; Bakhtiari, Kh.
Sodium selenate–catalyzed simple and efficient synthesis of tetrahydrobenzo[b]pyran

496
D. I. MAGEE ET AL.
derivatives. Catal. Commun. 2008, 9, 307–310; (f) Lian, X. Z.; Huang, Y.; Li, Y. Q.;
Zheng, W. J. A green synthesis of tetrahydrobenzo[b]pyran derivatives through three-
component condensation using N-methylimidazole as organocatalyst. Monatsh. Chem.
2008, 139, 129–131; (g) Balalaie, S.; Bararjanian, M.; Sheikh-Ahmadi, M.; Hekmat, S.;
Salehi, P. Diammonium hydrogen phosphate: An efficient and versatile catalyst for the
one-pot synthesis of tetrahydrobenzo[b]pyran derivatives in aqueous media. Synth. Com-
mun. 2007, 37, 1097–1108; (h) Balalaie, S.; Bararjanian, M.; Amani, A. M.; Movassagh, B.
(S)-Proline as a neutral and efficient catalyst for the one-pot synthesis of tetrahydroben-
zo[b]pyran derivatives in aqueous media. Synlett 2006, 263–266; (i) Li, J. T.; Xu, W. Z.;
Yang, L. C.; Li, T. S. One-pot synthesis of 2-amino-4-aryl-3-carbalkoxy-7,7-dimethyl-5,
6,7,8-tetrahydrobenzo[b]pyran derivatives catalyzed by KF=basic Al2O3 under ultrasound
irradiation. Synth. Commun. 2004, 34, 4565–4571; (j) Wang, X. S.; Shi, D. Q.; Tu, S. T.;
Yao, C. S. A convenient synthesis of 5-oxo-5,6,7,8-tetrahydro-4H-benzo-[b]-pyran deriva-
tives catalyzed by KF-alumina. Synth. Commun. 2003, 33, 119–126.
13. Zhu, J.; Bienaymeh, H. Multicomponent Reaction; Wiley-VCH Verlag: Weinheim, 2005;
pp. 438–447.
14. Ramachary, D. B.; Barbas III, C. F. Towards organo-click chemistry: Development
of organocatalytic multicomponent reactions through combinations of aldol, Wittig,
Knoevenagel, Michael, Diels–Alder, and Huisgen cycloaddition reactions. Chem. Eur.
J. 2004, 10, 5323–5331.
15. Akritopoulou-Zanze, I.; Gracias, V.; Djuric, S. W. A versatile synthesis of fused triazolo
derivatives by sequential Ugi=alkyne-azide cycloaddition reactions. Tetrahedron Lett.
2004, 45, 8439–8441.
16. Gracias, V.; Darczak, D.; Gasiecki, A. F.; Djuric, S. W. Synthesis of fused triazolo-
imidazole derivatives by sequential van Leusen=alkyne-azide cycloaddition reactions.
Tetrahedron Lett. 2005, 46, 9053–9056.
17. (a) Sreedhar, B.; Reddy, P. S.; Kumar, N. S. Cu(I)-catalyzed one-pot synthesis of 1,4-
disubstituted 1,2,3-triazoles via nucleophilic displacement and 1,3-dipolar cycloaddition.
Tetrahedron Lett. 2006, 47, 3055–3058; (b) Chandrasekhar, S.; Basu, D.; Rambabu, Ch.
Three-component coupling of alkynes, Baylis–Hillman adducts, and sodium azide: A
new synthesis of substituted triazoles. Tetrahedron Lett. 2006, 47, 3059–3063.
18. Khanetskyy, B.; Dallinger, D.; Kappe, C. O. Combining Biginelli multicomponent and
click chemistry: Generation of 6-(1,2,3-triazol-1-yl)-dihydropyrimidone libraries. J. Comb.
Chem. 2004, 6, 884–892.
19. (a) Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Bodaghi Fard, M. A. Silica sulfuric acid: An
efficient and reusable catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1-
H)-ones. Tetrahedron Lett. 2003, 44, 2889–2891; (b) Dabiri, M.; Delbari, A. S.; Bazgir,
A.
A novel three-component, one-pot synthesis of 1,2-dihydro-1-aryl-naphtho[1,
2-e][1,3]oxazine-3-one derivatives under microwave-assisted and thermal solvent-free
conditions. Synlett 2007, 821–823; (c) Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Otokesh,
S.; Baghbanzadeh, M. Selective synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles
in water at ambient temperature. Tetrahedron Lett. 2006, 47, 2557–2560; (d) Dabiri,
M.; Baghbanzadeh, M.; Arzroomchilar, E. 1-Methylimidazolium triflouroacetate
([Hmim]TFA): An efficient reusable acidic ionic liquid for the synthesis of 1,8-dioxo-
octahydroxanthenes and 1,8-dioxo-decahydroacridines. Catal. Commun. 2008, 9, 939–
942; (e) Dabiri, M.; Bahramnejad, M.; Baghbanzadeh, M. Ammonium salt–catalyzed
multicomponent transformation: Simple route to functionalized spirochromenes and
spiroacridines. Tetrahedron 2009, 65, 9443–9447; (c) Dabiri, M.; Bahramnejad, M.;
Bashiribod, S. TFA-catalyzed multicomponent reaction: Direct, mild, and efficient
procedure for the synthesis of 1,2-dihydroquinazoline derivatives. Mol. Divers. 2010, 14,
507–512.

1,2,3-TRIAZOLE-LINKED TETRAHYDROBENZO[b]PYRANS
497
20. Dabiri, M.; Salehi, P.; Bahramnejad, M.; Sherafat, F. Synthesis of diheterocyclic
a
compounds based on triazolyl methoxy phenylquinazolines via
four-component, click reaction. J. Comb. Chem. 2010, 12, 638–642.
one-pot,
21. Frixa, C.; Mahon, M. F.; Thompson, A. S.; Threadgill, M. D. Synthesis of meso-
substituted porphyrins carrying carboranes and oligo(ethylene glycol) units for potential
applications in boron neutron capture therapy. Org. Biomol. Chem. 2003, 1, 306–317.
22. (a) Bra¨se, S.; Gil, C.; Knepper, K.; Zimmermann, V. Organic azides: An exploding diver-
sity of a unique class of compounds. Angew. Chem., Int. Ed. Engl. 2005, 44, 5188–5240; (b)
Scriven, E. F. V.; Turnbull, K. Azides: Their preparation and synthetic uses. Chem. Rev.
1988, 88, 297–368.