Metal-free cycloaddition to synthesize naphtho[2,3-d][1,2,3]triazole-4,9-diones

Article abstract of DOI:10.1039/c5ob01322d

A metal-free domino [3 + 2] cycloaddition is reported to construct naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives and provide an alternative approach to the azide-alkyne cycloadditions. The key features are easily available starting materials, mild reaction conditions, a good atom economy, eco-friendly characteristics and a broad substrate scope with high yields.

Full text of DOI:10.1039/c5ob01322d

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: B. Chen, K. Kuo, J.
K. Vandavasi, S. S. K. Boominathan, C. Chen and J. Wang, Org. Biomol. Chem., 2015, DOI:
10.1039/C5OB01322D.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 6
View Article Online
DOI: 10.1039/C5OB01322D
Journal Name
ARTICLE
Metal Free Cycloaddition to Synthesize Naphtho[2,3-
d][1,2,3]triazole-4,9-diones
`Received 00th January 20xx,
Accepted 00th January 20xx
Bing-Fan Chen,a Kung-Kai Kuo,b Jaya Kishore Vandavasi, a Siva Senthil Kumar Boominathan, a
Chung-Yu Chen a and Jeh-Jeng Wang a*
DOI: 10.1039/x0xx00000x
A metal free domino [3+2] cycloaddition is reported to construct naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives and
an alternative approach to the azide-alkyne cycloadditions. The key features are easily available starting materials, mild
conditions, atom economy, eco-friendly and with broad substrate scope in high yields.
www.rsc.org/
several other applications.7-8 Recently, they are also
extensively utilized as ligands for catalysis,10 directing groups
for metal-catalyzed C−H activation,11 and as building blocks in
Introduction-
Lewis acid-promoted cycloadditions are widely utilized
approaches to construct useful heterocycles from simple
starting materials.1-2 Of particular importance, the [4+2], [4+1],
and [3+2] cycloadditions via intramolecular or intermolecular
type leads to build the biologically potent molecules.
In particular, [3+2] azide-alkyne cycloaddition reactions are
well explored with metal salts such as Cu(CuAAC), Ru(RuAAC)
and Ir(IrAAC).3-6 Among them, the copper (I) catalyzed cyclo
additions are well studied and the acetylide complexes are
formed by using copper with terminal alkynes, it accelerates
the cycloaddition reaction. Therefore, the CuAAC is limited to
terminal alkynes, whereas the internal alkynes are challenging
to react with azides to afford fully substituted triazoles due to
their weak reactivity and difficulty in regioselectivity. This turn
into a major problem of prevailing click reactions.
organic synthesis.12 The most common methods available in
the literature for synthesis of these scaffolds are less
explored.5c By considering these facts, there is a need for the
construction of fused triazoles by a simple method.9,13 As part
of our continuing research in the metal free reactions,14 we
herein envisioned a new metal free approach via oxidation
followed by the alcohol azide cycloaddition to afford
naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives (Fig 1, Eq
1b).
To overcome these drawbacks, recently some groups have
developed alternative methods for [3+2] alkyne-azide
cycloaddition reactions. In these reactions, the alkyne was
replaced by the ketones, enals, -ketoesters, and enones to
Figure 1 Substituted triazole synthesis.
give the respective 1,2,3-triazoles in high yields.7-9 In this
instance, recently Ramachary et. al., reported an efficient
method to prepare substituted triazoles by using aldehydes
and azides (Fig 1, Eq 1a).3a There is a demand in organic
synthesis of simple methods by a sequential process to lead
heterocyclic compounds. Inspired by this new concept, we
want to explore this area and synthesized substituted fused
triazoles from easily available staring materials as phenols or
napthols was initiated.
Results and Discussions
The optimization studies were initiated with the alcohol 1a in
the presence of CuI/m-CPBA/K2CO3 in DMF at room
temperature for 12h and then the azide 2a was added. The
desired compound 3a was obtained in 60% yield (Table 1,
entry 1). The reaction was screened with various copper salts
as CuBr, CuCl, CuSO4, Cu(OAc)2, Cu(OTf)2 and the yields are not
satisfactory (entries 2-6). Without an additive K2CO3 the
reaction yield was not varied (entry 7) and also without the
catalyst CuI (entries 8), the reaction yields were not varied
much from the entry 1. These results revealed that the catalyst
and additive were not essential for this transformation. We
next envisaged the feasibility of the reaction in the absence of
metal salt and additive. Different solvents as DMSO, THF, H2O,
Meanwhile, the fused triazoles have several biological
applications like antibacterial, antimycotic, anticancer and
a Department of Medicinal and Applied Chemistry, Kaohsiung Medical University,
Kaohsiung, Taiwan.
b Department of Surgery, School of Medicine, Kaohsiung Medical University,
Kaohsiung, Taiwan.
† Electronic Supplementary Information (ESI) available: [Experimental procedures,
characterization, and Crystal data]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 6
ARTICLE
Journal Name
improve the substrate scope, the substituted napthols were
MeOH, EtOH, PhMe, C6H6, MeCN were scrutinized (entries 9-
16) and among them DMF (entry 8) as shown the best result.
The temperature was elevated to 80 C and also increased to
100 oC, the reaction was good at 80 oC (entry 17-18). The yield
was not increased even though the reaction was carried out
for a longer time (entry 19). Finally, the entry 17 was chosen as
the optimum condition and by using this condition the
substrate scope is studied in Table 2 & 3.
View Article Online
tested. The electron donating group asD–OOI:M10e.103p9r/oCd5uOcBe0d132th2De
desired compound with moderate yield (3s). With electron
withdrawing group as –NO2 the product (3t) was observed in
low yield with inseparable isomers. The reaction with hydroxyl
substituted naphthol (3u) was failed.
o
Table 2 Scope of the reaction to synthesize naphtha [2,3-d][1,2,3]triazole-4,9-dione
derivatives. a, b
Table 1 Optimization of reaction conditions to synthesize compound 3a a
Entry
1
2
3
4
5
6
7
8
Oxidant
CuI/ m-CPBA
CuBr/ m-CPBA
CuCl/ m-CPBA
CuSO4/ m-CPBA
Cu(OAc)2/ m-CPBA
Cu(OTf)2/ m-CPBA
CuI/ m-CPBA
m-CPBA
Solvent Temp
Additive
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
none
none
none
none
none
none
none
none
none
none
none
none
none
3ab
60
21
13
8
20
16
55
57
35
42
15
8
11
20
17
19
76
73
70
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
THF
rt
rt
rt
rt
rt
rt
rt
rt
rt
9
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
m-CPBA
10
11
12
13
14
15
16
17
18
19c
rt
H2O
rt
MeOH
EtOH
PhMe
C6H6
rt
rt
rt
rt
MeCN
DMF
DMF
DMF
rt
m-CPBA
m-CPBA
m-CPBA
80
100
80
a With 1 (1.0 mmol), m-CPBA (1.0 mmol) and DMF (2 mL) at 80 oC for 12 h then 2
(1.1 mmol) was added and stirred for 12 h. b Isolated yield. c 48 h.
With the optimized condition in hand, various
functionalized azides were studied to give the desired naphtha
[2,3-d][1,2,3]triazole-4,9-dione derivatives (Table 2). The aryl
azides with electron donating groups as -OMe and -Me has
given good yields 3a-3e. The simple phenyl azide also tolerated
well with the optimized conditions to give compound 3f. With
an electron withdrawing groups as F, Cl, Br and I groups the
reaction proceeded smoothly to give the compounds 3g-3l.
Whereas, with nitro aryl azide the reaction was not successful
to give the desired compound 3m. It may be due to the strong
electron withdrawing ability of -NO2, which could decrease the
nucleophilicity of azide. Next, we investigated the feasibility of
reaction with alkyl azides, the desired products were observed
in moderate yields (entries 3n and 3o). The study was
continued with benzyl azide and it was succeeded with yield
60% by giving the compound 3p. Surprisingly, the reactions
with di-azide aryl compounds the reaction was succeeded to
give the compounds 3q and 3r with moderate yields. To
a With 1 (1.0 mmol), m-CPBA (1.0 mmol) and DMF (2 mL) at 80 oC for 12 h then 2
(1.1 mmol) was added and stirred for 12 h. b Isolated yield.
Instead of napthols, the reaction scope was extended by
using phenol. Interestingly, the bis-triazole moieties were
observed with satisfactory yields (Table 3) by giving the
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 3 of 6
Journal Name
compounds 5a
ARTICLE
-
5c. The structures of compound 3f and 5b were reactions proceeded with moderate yields. Further
View Article Online
confirmed by X-ray analysis (Figure 2).15
optimization is required to increase the yields and they are
under investigation.
DOI: 10.1039/C5OB01322D
Table 3 Scope of the reaction to synthesize bistriazoles. a,b
3f
a With 1 (1.0 mmol), m-CPBA (1.0 mmol), and DMF (2 mL) at 80 oC for 12 h then 2
(2.0 mmol) added and stirred for 12 h. b Isolated yield.
5b
Figure 2. ORTEP diagram of 3f and 5b.
Table 4 One pot synthesis.
Scheme 1 Control experiments to confirm the mechanistic intermediates.
To understand the reaction mechanism, the control
experiments are studied in Scheme 1. To confirm the reaction
as it is following a radical pathway or cycloaddition, one pot
synthesis was carried in the presence of TEMPO a radical
scavenger. Surprisingly, the reaction was yielded with 57% of
desired compound 3a and the oxidized alcohol product 1a’
with yield 37% (Scheme 1A). This result shows that the one pot
reaction feasibility as well as the reaction intermediate is
quinone 1a’. Next, the reaction was conducted without the
TEMPO (Scheme 1B) and the reaction yield was not increased.
By these results it was clear that the reaction was not inhibited
by the TEMPO and the reaction is not proceeding via a radical
mechanism. The experiment with quinone 1a’ was carried
without an oxidant as m-CPBA and found that the reaction was
smoothly undergoing to deserve the required compound 3a
(Scheme 1C).
The above results encouraged us to perform one pot
method to synthesis naphtho[2,3-d][1,2,3]triazole-4,9-dione
derivatives and the results were shown in Table 4. The
a Reactions were performed with 1 (1.0 mmol), 2 (1.0 mmol) and m-CPBA (1.0
mmol), DMF (2 mL)at 80 oC for 24-40 h. b Isolated yield.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 6
ARTICLE
Journal Name
Based on these results, a plausible reaction mechanism 61.1, 56.4. HRMS (ESI-ion trap, m/s) calcd for CV1i9eHw1A5rNtic3leOO5nNlinae,
DOI: 10.1039/C5OB01322D
was proposed in Scheme 2. The starting material 1a was calcd 388.0909, found 388.0903.
oxidized in the presence of m-CPBA to give benzoquinone 1a’
The benzoquinone 1a’ undergoes a Michael type reaction to dione (3b):Yellow solid (74%). mp = 195-197 oC. 1H NMR
give an intermediate . It undergoes a concerted [3+2] (CDCl3, 400 MHz): δ 8.38 (dd, J = 7.2, 1.6 Hz, 1H), 8.21 (dd, J =
cycloaddition (Path A, intermediate ) or stepwise amination- 7.2, 1.2 Hz, 1H), 7.88-7.79 (m, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.11
cyclization reaction (Path B, intermediate
) to give the (d, J = 8.8 Hz, 2H), 3.92 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ
intermediate . Intermediate
give the final compound 3f
.
1-(4-methoxyphenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
A
A
B
C
C
undergoes dehydrogenation to 176.9, 174.3, 161.2, 145.7, 135.0, 134.4, 133.1, 133.0, 127.6,
127.5, 126.3, 114.3, 55.6. HRMS (ESI-ion trap, m/s) calcd for
C17H11N3O3Na, calcd 328.0698, found 328.0690.
.
1-(3-methoxyphenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
Scheme 2 A plausible mechanism for the synthesis of Naphtho[2,3-d][1,2,3]triazole-4,9-
dione (3c) : Yellow solid (72%). mp = 210-212 oC. 1H NMR
(CDCl3, 400 MHz): δ 8.39 (dd, J = 7.2, 1.6 Hz, 1H), 8.23 (dd,
J=7.6, 1.2 Hz, 1H), 7.89-7.80 (m, 2H), 7.53 (t, J = 8.0 Hz, 1H),
7.33 (dd, J = 8.0, 2.0Hz, 1H) ,7.286 (t, J = 2.4 Hz 1H) , 7.17 (dd, J
= 8.4, 2.4Hz, 1H), 3.91 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ
176.9, 174.1, 160.0, 145.8, 136.1, 135.1, 134.5, 133.1, 130.0,
127.7, 127.6, 117.1, 116.7, 110.7, 55.7. HRMS (ESI-ion trap,
m/s) calcd for C17H11N3O3Na, calcd 328.0698, found 328.0691
1-(2-methoxyphenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
dione (3d): Yellow solid (67%). mp = 222-226 oC. 1H NMR
(CDCl3, 400 MHz): δ 8.39 (dd, J = 7.6, 1.6 Hz, 1H), 8.17 (dd, J =
8.0, 1.6 Hz, 1H), 7.87-7.77 (m, 2H), 7.63 (td, J = 7.6, 1.6Hz 1H),
7.53 (dd, J = 7.6, 1.6Hz, 1H) ,7.19 (m, 2H) , 3.78 (s, 3H). 13C
NMR (CDCl3, 100 MHz): δ 177.0, 174.0, 153.8, 145.0, 134.9,
134.2, 133.3, 133.0, 132.4, 127.7, 127.3, 124.5, 120.7, 112.1,
55.8. HRMS (ESI-ion trap, m/s) calcd for C17H11N3O3Na, calcd
328.0698, found 328.0692.
dione derivatives.
Conclusions
In conclusion, we have developed a metal free synthesis via an
oxidation followed by [3+2] cycloaddition to produce
naptho[2,3-d][1,2,3]triazole-4,9-dione derivatives. For the first
time, we have developed
a
metal-free alcohol-azide
1-(p-tolyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
(3e):
cycloaddition to synthesize the substituted fused triazoles. The
notable features of the work include simple precursors,
environmentally benign conditions, and with broad substrate
scope.
Yellow solid (71%). mp = 126-128 oC. 1H NMR (CDCl3, 400
MHz): δ 8.35 (dd, J = 7.6, 1.6 Hz, 1H), 8.20 (dd, J = 7.6, 1.6 Hz,
1H), 7.88-7.79 (m, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.0
Hz, 1H), 2.50 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 176.9, 174.1,
145.7, 141.2, 135.0, 134.4, 133.1, 133.0, 132.9, 132.7, 129.7,
127.6, 127.5, 124.7, 21.3. HRMS (ESI-ion trap, m/s) calcd for
C17H11N3O2Na, calcd 312.0749, found 312.0741.
Experimental
General procedure for the synthesis of Compound 2:
phenyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione (3f): Beige
solid (68%). mp = 232-236 oC. 1H NMR (CDCl3, 400 MHz): δ 8.38
(dd, J = 7.2, 1.2 Hz, 1H), 8.22 (dd, J = 7.6, 1.2 Hz, 1H), 7.89-7.80
(m, 2H), 7.75-7.73 (m, 2H), 7.65-7.61 (m, 3H). 13C NMR (CDCl3,
100 MHz): δ 176.9, 174.2, 145.8, 135.2, 135.1, 134.5, 133.1,
133.0, 132.9, 130.8, 129.2, 127.7, 127.6, 125.0. HRMS (ESI-ion
trap, m/s) calcd for C16H9N3O2Na, calcd 298.0592, found
298.0585.
1-(4-fluorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
dione (3g): Beige solid (63%). mp = 252-254 oC. 1H NMR (CDCl3,
400 MHz): δ 8.39 (dd, J = 7.2, 1.6 Hz, 1H), 8.22 (dd, J = 7.6, 1.2
Hz, 1H), 7.90-7.81 (m, 2H), 7.78-7.73 (m, 2H), 7.34-7.28 (m,
2H). 13C NMR (CDCl3, 100 MHz): δ 176.8, 174.3, 164.9, 162.4,
145.8, 135.2, 134.5, 133.0, 127.7, 127.6, 127.1, 116.5, 116.3.
HRMS (ESI-ion trap, m/s) calcd for C16H8N3O2FNa, calcd
316.0498, found 316.0495.
Corresponding compound
DMF (2 mL) and the oxidant m-CPBA was (1.0 mmol) was
1 (100 mg, 1.0 mmol) was taken in
added and the reaction was monitored by TLC after stirring at
o
12h at 80 C. Then the compound
2 (1.0 mmol) was added to
the reaction mixture. The reaction was monitored by TLC after
stirring the reaction at 80 oC for 12h. The reaction mixture was
cooled to room temperature and then water was added.
Extracted with ethyl acetate (3 X 50 ml) followed by washing
with water and brine. The combined extracts were dried over
Na2SO4 and concentrated to give a crude residue. This was
purified by flash column chromatography by using a gradient
system of hexane/ethyl acetate and obtained the desired pure
product
2.
1-(3,4,5-trimethoxyphenyl)-1H-naphtho[2,3-d][1,2,3]triazole-
o
1
4,9-dione (3a): Yellow solid (76%). mp = 232-234 C. H NMR
(CDCl3, 400 MHz): δ 8.39 (dd, J = 7.2, 1.2 Hz, 1H), 8.25 (dd, J =
7.2, 1.2 Hz, 1H), 7.88-7.83 (m, 2H), 7.02 (s, 2H), 3.96 (s, 3H)
3.95 (s, 6H). 13C NMR (CDCl3, 100 MHz): δ 176.9, 174.2, 153.3,
145.8, 139.8, 135.1, 134.5, 133.1, 132.9, 130.6, 127.7, 102.7,
1-(4-chlorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
dione (3h): Yellow solid (75%). mp = 220-222 oC. 1H NMR
(CDCl3, 400 MHz): δ 8.38 (dd, J = 7.6, 1.6 Hz, 1H), 8.22 (dd, J =
7.6, 1.6 Hz, 1H), 7.90-7.81 (m, 2H), 7.73 (d, J = 9.2 Hz, 2H), 7.61
(d, J = 9.2 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 176.7, 174.2,
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 5 of 6
Journal Name
ARTICLE
145.9, 136.9, 135.2, 134.5, 133.6, 132.9, 129.5, 127.7, 127.6, 128.6, 128.9, 127.8, 127.3, 123.5, 53.7. HRMS (ESI-ion trap,
View Article Online
DOI: 10.1039/C5OB01322D
126.2. HRMS (ESI-ion trap, m/s) calcd for C16H8N3O2ClNa, calcd m/s) calcd for C16H8N3O2ClNa, calcd 312.0749, found 312.0743.
332.0203, found 332.0199.
1-(3-chlorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
1-(4-azidophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
1
(3q): Yellow solid (59%). mp = 172-176 oC. H NMR (CDCl3, 400
dione (3i) : Yellow solid (74%). mp = 212-214 oC. 1H NMR MHz): δ 8.37 (dd, J = 7.6, 1.6 Hz, 1H), 8.22 (dd, J = 7.6, 1.6 Hz,
(CDCl3, 400 MHz): δ 8.38 (dd, J = 7.2, 1.6 Hz, 1H), 8.23 (dd, J = 1H), 7.89-7.80 (m, 2H), 7.77 (d, J = 9.2 Hz, 2H), 7.26 (d, J = 9.2
7.2, 1.6 Hz, 1H), 7.90-7.81 (m, 2H), 7.80 (t, J = 2.0 Hz, 1H), 7.73 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 176.8, 174.2, 145.8,
(dt, J = 7.6, 1.2 Hz, 1H), 7.63-7.55 (m, 2H). 13C NMR (CDCl3, 100 142.7, 135.2, 134.5, 133.0, 132.9, 127.7, 127.6, 126.5, 119.6.
MHz): δ 176.7, 174.1, 145.9, 136.0, 135.3, 135.0, 134.5, 133.0, HRMS (ESI-ion trap, m/s) calcd for C16H8N6O2, calcd 316.0709,
130.9, 130.2, 127.7, 125.3, 123.2. HRMS (ESI-ion trap, m/s) found 316.0711.
calcd for C16H8N3O2ClNa, calcd 332.0203, found 332.0197.
1-(2-chlorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
1-(3-azidophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
(3r): Beige solid (57%). mp = 135-138 C. H NMR (CDCl3, 400
o
1
dione (3j): Beige solid (61%). mp = 238-242 oC. 1H NMR (CDCl3, MHz): δ 8.38 (dd, J = 7.2, 1.2 Hz, 1H), 8.23 (dd, J = 7.6, 1.6 Hz,
400 MHz): δ 8.40 (dd, J= 7.6, 1.2 Hz, 1H), 8.18 (dd, J = 7.6, 1.2 1H), 7.90-7.81 (m, 2H), 7.63 (t, J = 8.0 Hz, 1H), 7.55-7.522 (m,
Hz, 1H), 7.90-7.79 (m, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 1H), 7.44 (t, J = 2.4 Hz, 1H), 7.31-7.28 (m, 1H). 13C NMR (CDCl3,
9.2 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 176.7, 174.1, 145.0, 100 MHz): δ 176.7, 174.1, 145.9, 141.5, 136.4, 135.2, 134.5,
135.2, 134.9, 134.4, 133.2, 132.7, 132.3, 131.1, 130.5, 128.3, 133.0, 132.9, 130.5, 127.7, 121.3, 121.1, 115.9. HRMS (ESI-ion
127.8, 127.4. HRMS (ESI-ion trap, m/s) calcd for trap, m/s) calcd for C16H8N6O2, calcd 316.0709, found
C16H8N3O2ClNa, calcd 332.0203, found 332.0196.
316.0711.
1-(4-bromophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-
6-methoxy-1-(3-methoxyphenyl)-1H-naphtho[2,3-
dione (3k): Yellow solid (62%). mp = 250-252 oC. 1H NMR d][1,2,3]triazole-4,9-dione (3s): Yellow solid. mp = 148-151 oC.
(CDCl3, 400 MHz): δ 8.39 (dd, J = 7.6, 1.6 Hz, 1H), 8.23 (dd, J = 1H NMR (CDCl3, 400 MHz): δ 8.22 (d, J = 8.8 Hz, 1H), 7.55 (d, J =
7.6, 1.6 Hz, 1H), 7.91-7.82 (m, 2H), 7.69-7.52 (m, 4H). 13C NMR 2.8 Hz, 1H), 7.42 (t, J = 8.4 Hz, 1H), 7.23-7.18 (m, 3H), 7.06 (dd,
(CDCl3, 100 MHz): δ 176.7, 174.2, 145.9, 135.3, 134.5, 134.2, J = 8.8, 2.8 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H). 13C NMR (CDCl3,
132.9, 132.5, 127.8, 127.6, 126.4, 125.0. HRMS (ESI-ion trap, 100 MHz): δ 176.2, 174.1, 164.5, 160.0, 146.1, 136.1, 135.3,
m/s) calcd for C16H8N3O2ClNa, calcd 375.9698, found 375.9696. 133.3, 130.1, 129.9, 126.2, 120.7, 117.1, 116.7, 111.7, 110.7,
1-(4-iodophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
(3l): Beige solid (46%). mp = 251-254 C. H NMR (CDCl3, 400 5-nitro-1-(3,4,5-trimethoxyphenyl)-1H-naphtho[2,3-
MHz): δ 8.39 (dd, J = 7.6, 1.6 Hz, 1H), 8.23 (dd, J = 7.6, 1.6 Hz, d][1,2,3]triazole-4,9-dione (3t): Yellow sticky mass. The
56.0, 55.7.
o
1
1
1H), 7.98 (d, J = 8.4Hz, 2H), 7.90-7.81 (m, 2H), 7.52(d, J = 8.4 isomers are inseparable. HNMR was attached in supporting
Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 177.0, 174.4, 146.2, information for reference. 1H NMR (CDCl3, 400 MHz): δ 8.37 (d,
138.7, 135.5, 134.8, 133.4, 133.2, 128.0, 127.9, 126.7, 97.0. J = 8.0 Hz, 1H), 8.16 (t, J = 14.4 Hz, 1H), 7.96-7.85 (m, 2H), 7.75-
HRMS (ESI-ion trap, m/s) calcd for C16H8N3O2ClNa, calcd 7.71 (m, 1H), 6.94 (s, 1H), 6.41 (s, 1H), 3.89-3.77 (m, 11H).
375.9698, found 375.9696.
1,7-bis(3,4,5-trimethoxyphenyl)benzo[1,2-d:4,5-
1-pentyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
(3n): d']bis([1,2,3]triazole)-4,8(1H,7H)-dione (5a): Beige solid (62%).
Yellow solid (49%). mp = 88-90 oC. 1H NMR (CDCl3, 400 MHz): δ mp = 256-258 C. H NMR (CDCl3, 400 MHz): δ 6.90 (s, 2H),
8.33 (dd, J = 6.8, 1.6 Hz, 1H), 8.24 (dd, J = 7.2, 1.6 Hz, 1H), 7.86- 3.93 (s, 3H), 3.89 (s, 6H). 13C NMR (CDCl3, 100 MHz): δ 170.0,
7.82 (m, 2H), 4.87 (t, J = 7.2 Hz, 2H), 2.06-1.99 (q, J = 7.2 Hz 163.5, 153.4, 146.1, 140.1, 134.0, 130.0, 102.9, 61.0, 56.51.
2H), 1.43-1.36 (m, 4H), 0.93 (t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, HRMS (ESI-ion trap, m/s) calcd for C16H8N6O2, calcd 545.1397,
100 MHz): δ 176.7, 175.3, 145.4, 135.0, 134.2, 133.2, 132.7, found 545.1393.
o
1
127.7, 127.2, 50.5, 29.6, 28.3, 21.9, 13.7. HRMS (ESI-ion trap, 1,7-bis(4-methoxyphenyl)benzo[1,2-d:4,5-
m/s) calcd for C16H8N3O2ClNa, calcd 292.1062, found 292.1054. d']bis([1,2,3]triazole)-4,8(1H,7H)-dione (5b): Yellow solid
1-decyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
(3o): (57%). mp = 230-232 oC. 1H NMR (CDCl3, 400 MHz): δ 7.56 (d, J
Beige solid (53%). mp = 88-90 C. H NMR (CDCl3, 400 MHz): δ = 9.2 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 3.88 (t, 3H). 13C NMR
8.31 (dd, J = 6.8, 1.6 Hz, 1H), 8.22 (dd, J = 7.2, 1.6 Hz, 1H), 7.88- (CDCl3, 100 MHz): δ 170.0, 163.8, 161.4, 146.1, 133.8, 127.5,
7.80 (m, 2H), 4.87 (t, J = 7.2 Hz, 3H), 2.06-1.99 (m, 2H), 1.43- 126.4, 114.4, 55.6. HRMS (ESI-ion trap, m/s) calcd for
1.25 (m, 14H), 0.88 (t, J = 6.4 Hz, 3H). 13C NMR (CDCl3, 100 C16H8N6O2, calcd 425.0974, found 425.0969.
o
1
MHz): δ 176.6, 175.2, 145.3, 135.0, 134.1, 133.1, 127.5, 127.1, 1,7-bis(2,4-dimethylphenyl)benzo[1,2-d:4,5-
50.5, 31.6, 29.8, 29.2, 29.0, 28.7, 26.1, 22.4, 13.9. HRMS (ESI- d']bis([1,2,3]triazole)-4,8(1H,7H)-dione (5c): Beige solid (60%).
o
1
ion trap, m/s) calcd for C20H25N3O2Na, calcd 362.1844, found mp = 157-159 C. H NMR (CDCl3, 400 MHz): δ 7.18(m, 3H),
362.1839.
2.39 (s, 3H), 2.04 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 170.0,
benzyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione (3p): Beige 163.6, 145.9, 141.7, 134.8, 133.9, 131.9, 131.5, 127.6, 126.2,
solid (60%). mp = 119-123 oC. 1H NMR (CDCl3, 400 MHz): δ 8.33 21.2, 17.2.
(dd, J = 7.2, 2.0 Hz, 1H), 8.23(dd, J = 7.2, 1.2 Hz, 1H), 7.89-7.75
(m, 2H), 7.52 (dd, J = 8.0, 2.0 Hz, 2H), 7.38-7.308 (m, 3H). 13C
NMR (CDCl3, 100 MHz): δ 176.7, 175.3, 145.6, 135.1, 134.2,
Acknowledgements
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 6
ARTICLE
Journal Name
Chem., 2014, 2014, 6219; (b) S. S. K. Boominathan, W.-P. Hu,
We thank the MOST of Taiwan for financial support. We thank
the Center for Research Resources and Development of
Kaohsiung Medical University for providing the service of NMR
400MHz-JEOL.
G. C. Senadi, J. K. Vandavasi and J.-J. Wang, CheVmiew. CAortimclemOunlnin.e,
DOI: 10.1039/C5OB01322D
2014, 51, 6726; (c) C. Y. Chen, W.-P. Hu, P. C. Yan, G. C.
Senadi and J.-J. Wang, Org. Lett., 2013, 15, 6116; (d) C. Y.
Chen, W.-P. Hu, M. C. Liu, P. C. Yan, J.-J. Wang and M. I.
Chung, Tetrahedron, 2013, 69, 9735; (e) J. K. Vandavasi, W.-
P. Hu, H. Y. Chen, G. C. Senadi, C. Y. Chen and J.-J. Wang, Org.
Lett., 2012, 14, 3134; (f) W. C. Lee, H. C. Shen, W.-P. Hu, W.
S. Lo, C. Murali, J. K. Vandavasi and J.-J. Wang, Adv. Synth.
Catal., 2012, 354, 2218.
Notes and References
1
(a) A. J. Kochanowska-Karamyan and M. T. Hamann, Chem.
Rev., 2010, 110, 4489; (b) C. L. Sun, H. Li, D.-G. Yu, M. Yu, X.
Zhou, X.-Y. Lu, K. Huang, Z.-B. Zheng and J. Shi, Nat. Chem.,
15 CCDC numbers for the compounds 3f and 5b are 1409273-
1409274.
2010, 2, 1044; (c) S. L. Schreiber, Science 2000, 287, 1964; (d)
H. Wamhoff, In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984;
Vol. 5, pp 669; (e) M. Lautens, W. Klute and W. Tam, Chem.
Rev., 1996, 96, 49.
2
3
(a) J. P. Lin, F. H. Zhang and Y. Q. Long, Org. Lett., 2014, 16,
2822; (b) R. S. Lewis, M. F. Wisthoff, J. Grissmerson and W. J.
Chain, Org. Lett., 2014, 16, 3832; (c) K. B. Manjappa, W. F.
Jhang, S. Y. Huang and D. Y. Yang, Org. Lett., 2014, 16, 5690;
(d) C. Allais, J. M. Grassot, J. Rodriguez and T. Constantieux,
Chem. Rev., 2014, 114, 10829.
(a) D. B. Ramachary, A. B. Shashank and S. Karthik Angew.
Chem., Int. Ed., 2014, 53, 10420; (b) A. B. Shashank, S.
Karthik, D. B. Ramachary and R. Madhavachary, Chem. -Eur.
J., 2014, 20, 16877; (c) D. B. Ramachary and A. B. Shashank,
Chem. -Eur. J. 2013, 19, 13175; (d) G. C. Senadi, W.-P. Hu, S.
S. K. Boominathan and J.-J.Wang, Adv. Syn. Catal., 2013, 355
3679.
,
4
5
(a) M. Belkheira, D. E. Abed, J.-M. Pons and C. Bressy, Chem.
-Eur. J., 2011, 17, 12917; (b) D. K. J. Yeung, T. Gao, J.
Huang, S.
Sun, H.
Guo
and J.
Wang, Green
Chem., 2013, 15, 2384; (c) W. Li, Z. Du, J. Huang, Q. Jia, K.
Zhang and J. Wang, Green Chem., 2014, 16, 3003.
(a) L. J. T. Danence, Y. Gao, M. Li, Y. Huang and J.
Wang, Chem. -Eur. J., 2011, 17, 3584; (b) W. Li, Q. Jia, Z. Du
and J. Wang, Chem. Commun., 2013, 49, 10187; (c) Q. Zhang,
J. P. Shrestha and C. W. T. Chang, Tetrahedron Lett., 2014,
55, 1839 (cited therein).
6
7
A. C. Bꢀdard and S. K. Collins, Org. Lett., 2014, 16, 5286.
(a) J. P. Shrestha and C. W. T. Chang, Bioorg. Med. Chem.
Lett., 2013, 23, 5909; (b) K. S. Babu, X.-C. Li, M. R. Jacob, Q.
Zhang, S. I. Khan, D. Ferreira and A. M. Clark, J. Med. Chem.
2006, 49, 7877.
8
9
(a) M. S. Wrighton, Science, 1986, 231, 32; (e) M. K. Dhaon, S.
R. Lehrman, D. H. Rich, J. A. Engelke and J. W. Suttie, J. Med.
Chem., 1984, 27, 1196; (b) D. R. Buckle, H. Smith, B. A. Spicer
and J. M. Tedder, J. Med. Chem., 1983, 26, 714. (c) S.
Inayama, K. Mamoto, T. Shibata and T. Hirose, J. Med.
Chem., 1976, 19, 433.
(a) B. H. Rotstein, S. Zaretsky, V. Rai and A. K. Yudin, Chem.
Rev., 2014, 114, 8323; (b) E. D. Anderson, A. S. Duerfeldt, K.
Zhu, C. M. Glinkerman and D. L. Boger, Org. Lett., 2014, 16
5084.
,
10 H. Duan, S. Sengupta, J. L. Petersen, N. G. Akhmedov and X.
Shi, J. Am. Chem. Soc., 2009, 131, 12100.
11 X. Ye, Z. He, T. Ahmed, K. Weise, N. G. Akhmedov, J. L.
Petersen and X. Shi, Chem. Sci., 2013, 4, 3712.
12 A. V. Gulevich and V. Gevorgyan, Angew. Chem., Int. Ed.,
2013, 52, 1371.
13 (a) K. Mantelingu, Y. Lin and D. Seidel, Org. Lett., 2014, 16
,
5910; (b) H. Haneda, S. Eda, M. Aratani and T. Hamura, Org.
Lett., 2014, 16, 286; (c) L. C. Fang and R. P. Hsung, Org. Lett.,
2014, 16, 1826.
14 (a) J. K. Vandavasi, W.-P. Hu, G. C. Senadi, S. S. K.
Boominathan, H. Y. Chen and J.-J. Wang, Eur. J. Org.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins