Multicomponent cascade reaction: Dual role of copper in the synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline and their photophysical studies

Article abstract of DOI:10.1039/c5ra24048d

One-pot synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinolines through a multi-component reaction is demonstrated. The domino/cascade reaction proceeds via click reaction, in which 1,2,3-triazole motif augment methylene group reactivity/N-C bond formation/Knoevenagel condensation in sequence. Overall one C-C bond and three C-N bonds are formed in a single step. In addition, photophysical properties of these new compounds were studied and compound 5u emerged as good fluorogenic substrate with quantum yield ～0.21.

Full text of DOI:10.1039/c5ra24048d

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: N. N. Hunsur, S.
Amaroju, M. Nagarjuna Reddy, S. Narva, S. Jayanty and K. Chandrasekhar, RSC Adv., 2016, DOI:
10.1039/C5RA24048D.
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. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this 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/advances

Please do not adjust margins
Page 1 of 12
RSC Advances
View Article Online
DOI: 10.1039/C5RA24048D
Journal Name
ARTICLE
Multicomponent cascade reaction: Dual role of copper in the
synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline
and their photophysical studies
Received 00th January 20xx,
Accepted 00th January 20xx
Hunsur Nagendra Nagesh,a Amaroju Suresh,a Muthyala Nagarjuna Reddy,b Narva Suresh,a
Jayanty Subbalakshmi,a and Kondapalli Venkata Gowri Chandra Sekhara*
DOI: 10.1039/x0xx00000x
www.rsc.org/
One-pot synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinolines through multi-component reaction is
demonstrated. The domino/cascade reaction proceeds via click reaction, in which 1,2,3-triazole motif augment methylene
group reactivity/N–C bond formation/Knoevenagel condensation in sequence. Overall one C-C bond and three C–N bonds
are formed in a single step. In addition, photophysical properties of these new compounds were studied and compound 5u
emerged as good fluorogenic substrate with quantum yield ~ 0.21.
tethered molecules with pharmaceutical and fluorescence
application are depicted in Figure 1.7,8 Hranjec et al. explored the
expediency of benzimidazo[1,2-a]quinoline analogues in various
Introduction
Multi-component reactions (MCRs) surfaced out to be potentially
more efficient synthetic strategy, which attribute renaissance in the
organic synthesis to afford sustainable and diversity-oriented
functionalized molecules.1 In particular; metal catalysed MCRs are
the choice of interest in recent times2 owing to the instinctive
drawbacks involved in the multistep synthesis.
In this context, we focused our attention on MCR catalysed by
inexpensive and abundant copper salts to perform more than one
distinct catalytic process in one-pot. Various research groups have
revealed dual catalytic behaviour of copper3 viz., Swamy et al.
executed [3+2] cycloaddition between azide and alkyne to afford
1,2,3-triazole followed by intramolecular C5-H arylation and O-C
bond formation with haloarenes in sequence.3e,4 Sun et al.
synthesized benzo[f]indole-4,9-diones in which copper was lewis
acid and oxidative catalyst.5 Pawar et al. illustrated the role of
copper both in the generation of cyanide unit from N,N-
dimethylformamide–ammonia and in the cyanation of aryl halides.6
Hence we combined MCR and dual role of copper catalyst to
synthesize versatile molecules.
domain.9 Copious synthetic strategies are available to accomplish
this aza-fused heterocycle.10,11 In many instances the bottleneck to
facilitate the key step Knoevenagel condensation is pre-
functionalization of the methylene bridge with electron
withdrawing group (-CN, -CO2R, -COR, -SO2R) which restrict
synthetic modification of molecules. As a result, MCR emphasizing
dual role of copper to synthesize 1,2,3-triazole tethered
benzimidazo[1,2-a]quinolines
and
exploration
of
their
photophysical properties in the current study was undertaken.
We herein wish to demonstrate the synthesis of such molecules
starting from the non-activated readily prepared precursor like
1,2,3-triazole which was formed insitu and study its influence in
activating the methylene link to undergo Knoevenagel
condensation. Hitherto only couple of published examples exist
based on click and activate approach to synthesize 1,2,3-triazole
tethered 2-quinolinone and iminochromene.12 Furthermore,
advancement of this unique arena is not explored much, this
ingenuity opens the window for chemist to develop 1,2,3-triazole
anchored fused heterocycles. Thus; in one synthetic operation we
envisioned a three component domino process via click reaction/N–
C bond formation/Knoevenagel condensation (Figure 2).
To implement the above strategy, we earmarked to synthesize
1,2,3-triazole tethered benzimidazo[1,2-a]quinoline as these two
heterocyclic moieties are widely applicable in biological systems,
material chemistry, and especially as fluorescent sensors, dye-
sensitized solar cell etc.7-9 Some of the prominent 1,2,3-triazole
Results and Discussion
At the outset, we instigated to assemble the 1,2,3-triazole tethered
benzimidazo[1,2-a]quinolines in two step process as depicted in
Scheme 1. The reactants 2-(azidomethyl)-1H-benzo[d]imidazole (1a)
and phenylacetylene (3a) were subjected to [3+2] cycloaddition in
the presence of CuSO4.5H2O, sodium ascorbate in t-BuOH:H2O (1:1)
at rt for 30 min. After completion of reaction, diluted with water
and filtered the resultant solid to yield 2-((4-phenyl-1H-1,2,3-triazol-
1-yl)methyl)-1H-benzo[d]imidazole (4a) in 94%. The structure of
a.Department of Chemistry, Birla Institute of Technology and Science-Pilani,
Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R.R. Dist. Hyderabad,
500078, Telangana, India. E-mail: kvgc@hyderabad.bits-pilani.ac.in,
kvgcs@yahoo.com.
b.School of Chemistry, University of Hyderabad, Hyderabad, 500046, Telangana,
India.
†Electronic Supplementary Information (ESI) available: photophysical data, copies
of NMR spectra for products. 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
RSC Advances
Page 2 of 12
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5RA24048D
Figure 1 1,2,3-triazole tethered molecules of pharmaceutical
and fluorescence application.7,8
Scheme 1 Synthesis of target molecule over two step
procedure
Figure
2
Design strategy of 1,2,3-triazole appended
Scheme 2 Synthesis of target molecule in one-pot
benzimidazo[1,2-a]quinoline
even with longer reaction time didn’t influence the yield much
(entry 2 and 3). Picolinic acid was found to be the ideal ligand which
promulgated the reaction to afford tandem product in 52% yield
(entry 4). Later effect of various bases was scrutinized (entry 5-8).
KOt-Bu and DBU equally suppressed the reaction yielding a complex
reaction mixture and K3PO4 took a longer reaction time (10 h) with
significant increase in the yield (entry 7, 72%). Gratifyingly, K2CO3
emerged to be the best possible base to afford the product in 89%
yield (entry-8). Further the effectiveness of various copper catalysts
was examined (entry 9-11). CuBr and CuCl were found to give
diminished yields while, Cu2O was found to be detrimental and
resulted in a complex reaction mass. Subsequently, the effect of
altering polar protic and aprotic solvent was assessed (entry 12-19).
Polar aprotic solvent in general did not fetch amenable yield, while
acetonitrile and water afforded solely triazole 4a. Nevertheless,
polyethylene glycol (PEG-400) at 100 ºC for 18 h yielded 86% of
product (entry 15). Decrease in the yield was observed when lower
loadings of CuI (0.05 mmol), picolinic acid (0.1 mmol) (entry 16) and
K2CO3 (2.5 mmol) (entry 17) were used. Taking advantage of PEG-
400 which is less toxic and environmentally benign solvent, we
attempted the tandem reaction at 120 ºC. Strikingly, the condition
revealed to be superior to all other solvent choices affording the
product in 93% yield (entry 18). Thus the catalytic system employing
CuI (0.1 mmol), picolinic acid (0.2 mmol) and K2CO3 (3 mmol) in
PEG-400 at 120 ºC for 8 h revealed to be optimal in realizing this
synthetic strategy.
1
product 4a was confirmed from its analytical data. In the H NMR
spectrum, methylene (–CH2–) bridged protons resonated at δ 5.89
ppm and a singlet at 8.05 ppm resonated due to the C5-H of 1,2,3-
triazole. Later, we treated 4a with 2-bromobenzaldehyde (2a) in the
presence of CuI (0.1 mmol)/TMEDA (0.2 mmol)/Cs2CO3 (3 mmol) in
DMSO at 100 ºC for 18 h under N2 atmosphere. To our delight, we
isolated the desired product 5a in 44% yield. The structure of 5a
was characterised by spectral data. In the 1H NMR spectrum,
disappearance of a singlet at δ 5.89 ppm due to methylene (–CH2–)
bridged protons and a broad peak at δ 12.2 ppm due to
benzimidazole N-H were noticed. Also a singlet appeared at δ 9.84
ppm for highly deshielded C5-H along with other protons at their
respective positions amply warranted the product formation. With
this appealing and heartening result handy, we focussed to alleviate
this sequential transformation.
As a next step, we steered our attempts to carry out MCR by
employing
2-(azidomethyl)-1H-benzo[d]imidazole
(1a),
2-
bromobenzaldehyde (2a) and phenylacetylene (3a) as condensation
partners. These three components were mixed with CuI (0.1
mmol)/TMEDA (0.2 mmol/Cs2CO3 (3 mmol) in DMSO and were
heated at 100 °C for 18 h under N2 atmosphere. After purification,
we isolated the desired product in 36% yield and in this process
overall four new bonds (1C-C and 3C-N) were formed in a single
step (Scheme 2). With this encouraging result, we then focused our
attention towards optimizing the reaction condition by screening
various parameters like catalysts, ligands, bases, solvents and
temperature to obtain a satisfactory yield for this MCR and the
results are summarized in Table 1.
With this fine-tuned MCR, further efforts were stream-lined to
expand the generality and scope of this methodology by varying
different alkynes (Table 2). Hyperconjugated systems 4-
ethynyltoluene and 4-tert-butylphenylacetylene reacted smoothly
to afford the desired products in 88 and 72% yield respectively (5b
and 5c, Table 2). Electron-withdrawing phenylacetylenes bearing
An augment in the yield (43%) along with accelerating reaction time
(8 h) was noticed when utility of L-proline was tested (Table 1, entry
1). Among others, 1,10-phenanthroline and 8-hydroxyquinoline
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 12
RSC Advances
Please do not adjust margins
Journal Name
ARTICLE
-Cl, -F and -CF3 groups enhanced the yield of desired product 5e To our surprise, the reaction was clean and the desirVeidewpArroticdleuOctnli5nke
(75%), 5f (87%) and 5g (80%) when compared to electron-rich was obtained in 67% yield. Furthermore, DtOoI:s1t0u.d10y39th/Ce5RreAa24c0ti4v8itDy
phenylacetylene 5d (-OMe, 72% yield). To make this protocol profile with alkyne, 2-ethynylpyridine was subjected to this MCR.
virtually more efficient, we sketched towards dealing with low As evident the alkyne smoothly participated in this cascade reaction
boiling aliphatic alkynes.
to afford the tandem product 5l in 76% yield.
Primarily, cyclopropylacetylene was subjected to MCR following our We then proceeded to evaluate the scope of substituted 2-
optimized condition. Unexpectedly lower yield of desired product bromobenzaldehydes (Table 3). 2-bromobenzaldehyde with one
(5h, 43%) was noticed. As the boling point of the alkyne is low, electron-rich group (-OMe) at C5 position furnished tandem product
heating at higher temperature might have resulted in lower yield. In in good yield (5m, 64%), compared to 2-bromobenzaldehyde
order to circumvent the diminished yield, we slightly modified the comprising two methoxy groups at C4 and C5 position (5n, 52%).
procedure by mixing all the components of the reaction and stirred While, 2-bromo-5-chlorobenzaldehyde furnished the tandem
the resultant mixture at 50 °C for 1 h to predominantly favour the product 5o in good yield (67%). However, 2-bromobenzaldehyde
click reaction before elevating the operating temperature to 120 °C with electron-withdrawing group (-F) at C5 position was found to
for 8 h. Encouragingly, the reaction proceeded at ease resulting in favour the tandem reaction to provide 5p in 89% yield. As an
an improved yield of product (5h, 77%). This modified condition extension, we tested our optimized condition on ortho-halo
was conveniently employed to yield compound 5i in 71%. (hetero)aryl carboxaldehyde moieties to generate benzimidazo[1,2-
Subsequently, we used ethynyltrimethylsilane as alkyne partner. As a][1,8]naphthyridine derivatives. Such compounds have ample
expected, product 5j was isolated in 88% yield after removal of application in photophysical and biological properties such as
trimethylsilyl group due to the basic reaction medium along with
Table 2 Screening of diverse acetylenes for the MCRa
higher temperature. Continuing with the aliphatic acetylenes, we
decided to explore alkynes bearing unprotected alcohol functional
group; hence we carried the MCR with propargyl alcohol, 1a and 2a.
Table 1 Optimization of cascade reaction conditionsa
T(°C)/
Time
Entry Catalyst
Ligand
Base Solvent
Yieldb%
43
1
2
CuI
CuI
(L)-Proline Cs2CO3 DMSO 100/8 h
1,10-Phen-
Cs2CO3 DMSO 100/12 h
anthroline
42
8-Hydroxy-
quinoline
3
CuI
Cs2CO3 DMSO 100/12 h
46
4
5
CuI
CuI
CuI
CuI
CuI
Picolinic acid Cs2CO3 DMSO 100/8 h
52
CRc
CRc
72
Picolinic acid KOt-Bu DMSO 100/8 h
6
Picolinic acid DBU
DMSO 100/8 h
7
Picolinic acid K3PO4 DMSO 100/10 h
Picolinic acid K2CO3 DMSO 100/8 h
8
89
9
CuBr Picolinic acid K2CO3 DMSO 100/8 h
CuCl Picolinic acid K2CO3 DMSO 100/8 h
Cu2O Picolinic acid K2CO3 DMSO 100/8 h
79
10
11
12
13
14
15
16e
17f
18
19
47
CRc
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
Picolinic acid K2CO3
Picolinic acid K2CO3
Picolinic acid K2CO3
Picolinic acid K2CO3
Picolinic acid K2CO3
Picolinic acid K2CO3
Picolinic acid K2CO3
DMF
DMA
ACN
PEG
PEG
PEG
PEG
100/8 h
100/8 h
80/24 h
100/18 h
120/18 h
120/14 h
120/8 h
45
52
NRd
86
74
84
93
NRd
Picolinic acid K2CO3 Water 100/24 h
aQuantities used: 2-(azidomethyl)-1H-benzo[d]imidazole (1 mmol),
2-bromobenzaldehyde (1 mmol) and phenylacetylene (1 mmol),
catalyst (0.1 mmol), ligand (0.2 mmol), base (3 mmol), solvent (2
c
mL). byields are for isolated products. complex reaction mixture.
aQuantities used: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), CuI (0.1
mmol), picolinic acid (0.2 mmol), K2CO3 (3 mmol), PEG-400 (2 mL);
byields are for isolated products.
dno reaction, triazole 4a remained unconsumed (entry 14 - 81%;
entry 19 - 79%). eCuI (0.05 mmol), ligand (0.1 mmol). K2CO3 (2.5
f
mmol).
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
RSC Advances
Page 4 of 12
ARTICLE
Journal Name
fluorescent chemodosimeter for detection of anionic species, comparison to ligand free reaction with shorter reacVtiieownAtrtiimcleeOonlfin8e
OLEDs, cannabinoid Typically,
receptors.13
2-bromo-3- h. Hence, we implemented picolinic acid asDliOgaI:n1d0.t1o03a9c/cCe5lReAr2a4te04t8hDe
pyridinecarboxaldehyde reacted smoothly to deliver desired reaction for the synthesis of 1,2,3-triazole tethered
product in 81% yield (5q). Conversely, when 2-chloro-8-methyl benzimidazo[1,2-a]quinoline analogues.
quinoline-3-carboxaldehyde was employed, decrease in the yield To inquest the reaction sequence for the formation of tandem
was noticed (5r, 60%). It is also worth to mention that 5q and 5r product, we carried out two parallel reactions (Scheme 4). In first
took shorter reaction time (6 h) primarily attributing to the instance we performed N-arylation of 4a with bromobenzene and in
reactivity of heteroaryl halides by
substitution (SNAr) reaction via an addition-elimination with benzaldehyde employing the optimised reaction condition.
mechanism.14
Despite prolonged heating for 24 h, we did not notice N-arylated
a nucleophilic aromatic the second instance we carried out Knoevenagel condensation of 4a
Eventually, we turned our attention to explore the reactivity profile product in the former reaction and Knoevenagel condensed
of substituted 2-(azidomethyl)-1H-benzo[d]imidazole. Substituents product in the latter reaction, intermediate 4a remained
like -CH3, -Cl and -F reacted smoothly to furnish the desired product unconsumed. The failure of N-arylation could be attributed to the
in good yield (Table 4: 84%, 5s; 77%, 5t; 66%, 5u). This indicated steric effects rising from the methylene triazole in destabilizing the
that electronic effect on benzimidazole core doesn’t impede the copper complex or the absence of suitable coordinating group at
reactivity profile. By virtue of its reactivity, products were found to ortho position of bromobenzene. In the latter case, the methylene
exist as mixture of regioisomers in 1:1 ratio with substituents at C9 group sandwiched between 1,2,3-triazole and benzimidazole
and C10 position (position numbering on structures).
heterocycles was not active enough to take part in Knoevenagel
Furthermore, Verma et al. accounted for the utilization of condensation apparently due to the less acidic nature. Facts from
benzotriazole based ligands in copper catalysis to synthesize various the control experiment warranted us that the bottleneck for this
nitrogen heterocycles.15 Inspired by the remarkable ligand tandem process would be carbonyl group assisted N-arylation14b,16
properties of 1,2,3-triazole framework, we thus attempted the MCR followed by Knoevenagel condensation.
employing ligand free condition (Scheme 3). Accordingly, 1a and 3a
Table
4
Screening of diverse 2-(azidomethyl)-1H-
was coupled with 2-bromobenzaldehyde and 2-bromo-5-
fluorobenzaldehyde. The former reaction took 20 h to provide 5a in
58% yield and the latter took 22 h to provide 5p in 53% yield.
Nevertheless, ligand promoted reaction fetched desired product in
an appreciable yield (Table 2, 5a, 93% and Table 3, 5p, 89%) in
benzo[d]imidazoles for the MCRa
Table 3 Screening of diverse 2-bromo/chloro(hetero)aryl
aldehyde for the MCRa
aQuantities used: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), CuI (0.1
mmol), picolinic acid (0.2 mmol), K2CO3 (3 mmol), PEG-400 (2 mL);
byields are for isolated products.
aQuantities used: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), CuI (0.1
mmol), picolinic acid (0.2 mmol), K2CO3 (3 mmol), PEG-400 (2 mL);
byields are for isolated products.
Scheme 3 MCR employing ligand free condition
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 12
RSC Advances
Please do not adjust margins
Journal Name
ARTICLE
Table 5 Spectral properties of fluorophores 5a-ua
View Article Online
DOI: 10.1039/C5RA24048D
Stokes
Shift
(nm)
max
(nm)
em
 x 103
b
Compd
Øfluo
(nm) (dm3 mol-1 cm-1)
5a
5b
5c
5d
5e
5f
370, 266, 242 427 29.4, 100.8, 134.7 0.08
185
201
161
160
164
186
186
368, 264, 228 429 16.3, 72.4, 83.9
370, 266, 250 427 16.0, 86.6, 75.0
0.07
0.10
370, 268, 242 428 26.1, 110.4, 103.3 0.09
370, 264,246 428 22.1, 79.0, 75.9
368, 266, 241 427 20.6, 82.7, 87.1
370, 268, 242 428 16.4, 56.4, 60.1
0.09
0.08
0.09
Scheme 4 Control experiments
5g
5h
5i
228
428 79.3
0.02
0.11
0.08
0.08
0.10
0.03
200
155
158
154
187
200
366, 268, 242 423 23.3, 89.1, 72.5
366, 266, 242 424 4.4, 17.3, 16.0
368, 272, 242 426 14.1, 47.0, 43.3
370, 266, 242 429 19.1, 65.9, 68.8
5j
5k
5l
5m
240
440 140.8
421
5n
5o
5p
5q
384, 274, 242
50.0, 120.1, 163.9 0.13
202
192
169
189
444
376, 270, 242 434 12.7, 50.4, 59.3
376, 264, 246 433 8.6, 36.0, 34.6
0.05
0.07
0.15
378, 250
439 22.9, 71.1
432
Scheme 5 Plausible mechanistic pathway for the formation of
tandem product
5r
5s
5t
376, 274, 242
32.2, 98.0, 98.4
0.15
216
192
177
157
458
The plausible mechanistic pathway for this MCR based on the
outcome of control experiments and literature precedents is
deduced (Scheme 5). Primarily, click reaction between 1 and 3
resulted in the formation of compound 4 with augment in
methylene group reactivity. On the other hand, ortho-halo
(hetero)aryl carbonyl compound forms complex with copper
catalyst through oxidative addition to furnish intermediate I.
Compound 4 upon deprotonation in the presence of base and
metallation with the intermediate I would provide the intermediate
II. Ultimately, reductive elimination of II furnishes desired tandem
product 5 through domino process of N-arylation-Knoevenagel
condensation to complete the catalytic cycle.
From the literature, plethora of benzimidazo[1,2-a]quinoline core
has been established as good fluorophore.9c,9d Additionally, tailoring
1,2,3-triazole moiety on to the existing fluorophores have endowed
remarkable photophysical properties.8d,17 We therefore opted to
examine the UV and fluorescence properties of diversely oriented
1,2,3-triazole tethered benzimidazo[1,2-a]quinoline backbone and
the spectral properties are summarised in Table 5 (For details see
372, 268, 242 434 19.8, 88.6, 111.0 0.12
368, 268, 248 425 21.7, 73.9, 78.9
368, 266, 248 423 11.4, 25.5, 25.0
0.06
0.21
5u
aMeasured in CHCl3 at 25 °C. bMeasured with quinine sulphate in
0.1M H2SO4 as standard.
supporting information S5-S6). The quantum yield was determined
in CHCl3 solution (within a maximum absorbance close to 0.1) and
was calculated relative to the quantum yield of standard compound
quinine sulphate in 0.1M H2SO4 (Øfluo = 0.54) at 25 ºC.18 Newly
synthesized fluorophores could function as versatile feedstock for
biological applications owing to the high extinction coefficients
(>150 nm).
Considering the electronic effects on 1,2,3-triazole moiety (5a-g and
5l) introduced by the substitution on the phenyl group, both
electron-donating and withdrawing substituents resulted in modest
quantum yield. Among the aliphatic system (5h-k), cyclopropyl
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
RSC Advances
Page 6 of 12
ARTICLE
Journal Name
group leading to compound 5h resulted in prejudicial quantum Figure 3 Absorption and emission spectra of 5q, 5r and 5u in CHCl3
View Article Online
DOI: 10.1039/C5RA24048D
yield, whereas employing acyclic n-butyl group affording compound at 25 °C.
5i resulted in cumulative quantum yield. Electron donating
substituent with dimethoxy group on the quinoline fragment
resulted in improved quantum yield in comparison to electron
withdrawing substituents (5o and 5p). Enhanced quantum yield was
observed on hopping to heterocyclic moieties (5q and 5r).
Eventually, though electron withdrawing (-F) substituent (5u) is
present on the benzimidazole core, this molecule possessed high
quantum yield of 0.21, probably due to the contribution from lone
pair of electrons on -F substituent and presence of rich -electron
system. Absorption and emission spectra of 5q, 5r and 5u in CHCl3 eter and fluorescence spectra were recorded using Jasco FP-6300
at 25 °C is shown in Figure 3.
spectrofluorometer.
1. Experimental procedure for synthesis of substituted 2-
(azidomethyl)-1H-benzo[d]imidazole:
Conclusions
Step 1: Substituted 2-(chloromethyl)-1H-benzo[d]imidazole was
prepared according to the literature procedure.19 Substituted o-
phenylenediamine (0.05 mol), chloroacetic acid (0.075 mol) and 4N
hydrochloric acid (50 mL) was heated under reflux for 45 minutes.
The mixture was allowed to stand overnight, diluted with 100 mL of
water, cooled and neutralized with sodium bicarbonate. The
resultant solid was filtered, washed with cold water and dried over
vacuum. The crude product was taken as such for the step 2
without further purification.
Step 2: Substituted 2-(azidomethyl)-1H-benzo[d]imidazole was
prepared according to the literature procedure.19 Substituted 2-
(chloromethyl)-1H-benzo[d]imidazole (0.05 mol) and NaN3 (0.055
mol) in DMSO (40 mL) was stirred at room temperature. The
reaction was monitored by TLC. After completion, diluted with 100
mL of water and extracted with diethyl ether (10 mL x 3). The
combined organic extracts were washed with brine, and dried over
anhydrous Na2SO4. After the organic solvent was removed under
reduced pressure, the residue was purified by column
chromatography to provide the title compound.
In conclusion, the present MCR deals with a facile and direct avenue
to synthesize versatile 1,2,3-triazole anchored benzimidazo[1,2-
a]quinolines. An ease of operation employing dual catalytic system
with low catalyst loading and PEG-400 as an environmentally benign
solvent crafts this protocol to be more appealing and synthetically
efficient. The domino process revealed good tolerance to various
substrates affording desired products in moderate to good yield. It
is apparent that click and activate approach could serve as a novel
platform to engineer immensely decorated 1,2,3-triazole anchored
nitrogenous fused heterocyclic framework. 1,2,3-triazole motif
revealed to be moderately electron withdrawing in activating the
adjacent methylene linker to undergo Knoevenagel condensation.
Owing to the high extinction coefficients (>150 nm), these
molecules could function as versatile feedstock for biological and
fluorescent applications. As the current investigation rendered
promising fluorophore properties, customization with appropriate
substituents and chromophores to generate essential fluorogenic
substrates is under exploration in our laboratory.
2-(azidomethyl)-1H-benzo[d]imidazole (1a):
Experimental
General :
Off-white solid, 6.5 g 75%, m.p. 120-121 °C; IR νmax (KBr) 2103,
1433, 1309, 1271, 1031, 997, 747 cm-1; Characterization details (1H
and 13C NMR) correlate with the literature reports.19
Chemicals and solvents were procured from commercial sources
and are analytically pure. Thin-layer chromatography (TLC) was
carried out on aluminium-supported silica gel plates (Merck 60
F254) with visualization of components by UV light (254 nm).
Column chromatography was carried out on silica gel (Merck 230-
400 mesh). 1H and 13C NMR spectra were recorded at 400 MHz
using a Bruker AV 400 spectrometer (Bruker CO., Switzerland) in
CDCl3 or DMSO-d6 solution with tetramethylsilane as the internal
standard, and chemical shift values (δ) are given in ppm. Some of
the compound’s 1H and 13C NMR spectra were recorded by addition
of 10 µL of formic acid or trifluoroacetic acid to the CDCl3 solution
due to the solubility issues. IR spectra were recorded on a FT-IR
spectrometer (Shimadzu) and peaks are reported in cm-1. Melting
points were determined on an electro thermal melting point
apparatus (Stuart-SMP30) in open capillary tubes and are
uncorrected. High resolution mass spectra (HRMS) were recorded
on a QSTAR XL Hybrid MS/MS mass spectrometer. UV-Visible
absorption spectra were recorded using Jasco V-650 spectrophotom
2-(azidomethyl)-5-methyl-1H-benzo[d]imidazole (1b):
Beige solid, 7.6 g 82%, m.p. 102-103 °C; IR νmax (KBr) 2173, 2103,
1450, 1326, 1280, 1254, 1188, 1140, 1027, 801 cm-1; H NMR (400
1
MHz, CDCl3) δ 7.50 (d, J = 8.2 Hz, 1H), 7.38 (s, 1H), 7.11 (dd, J = 8.4,
1.3 Hz, 1H), 4.73 (s, 2H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
148.64, 138.19, 137.02, 133.14, 124.67, 115.33, 114.66, 48.45,
21.81.
2-(azidomethyl)-5-chloro-1H-benzo[d]imidazole (1c):
Light brown solid, 7.4 g 72%, m.p. 112-113 °C; IR νmax (KBr) 2178,
2105, 1424, 1318, 1276, 1061, 1023, 800 cm-1; H NMR (400 MHz,
1
CDCl3) δ 7.61 (s, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.30 – 7.26 (m, 1H),
4.79 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 149.57, 132.46, 132.28,
130.44, 127.04, 115.43, 114.39, 45.65.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 12
RSC Advances
Please do not adjust margins
Journal Name
2-(azidomethyl)-5-fluoro-1H-benzo[d]imidazole (1d):
ARTICLE
6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5a)
View Article Online
DOI: 10.1039/C5RA24048D
Light brown solid, 6.3 g 68%, m.p. 81-82 °C; IR νmax (KBr) 2186, 2101, Colorless solid, 335 mg 93%, m.p. 216-217 °C; IR νmax (KBr) 3033,
1
1
1445, 1328, 1256, 1139, 1027, 860, 809 cm-1; H NMR (400 MHz, 1538, 1453, 1397, 1245, 1202, 1016, 898, 756 cm-1; H NMR (400
CDCl3) δ 7.46 (m, 1H), 7.21 (m, 1H), 6.98 (m, 1H), 4.69 (s, 2H); 13C MHz, CDCl3) δ 9.84 (s, 1H), 8.70 (d, J = 8 Hz, 1H), 8.68 (s, 1H), 8.51
1
NMR (100 MHz, CDCl3) δ 158.62 (d, JCF = 240.38 Hz), 150.00, (d, J = 8.5 Hz, 1H), 8.14 (d, J = 6.9 Hz, 1H), 8.06 (t, J = 8.5 Hz, 3H),
138.31, 134.99, 116.04 (d, 3JCF = 10.1 Hz), 111.59 (d, 2JCF = 25.25 Hz), 7.90 – 7.83 (m, 1H), 7.69 – 7.56 (m, 3H), 7.52 (t, J = 7.6 Hz, 2H), 7.41
101.21 (d, 2JCF = 27.27 Hz), 48.39.
(t, J = 7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 147.10, 138.23,
137.24, 132.76, 131.71, 130.33, 128.91, 128.16, 128.04, 127.41,
2. Experimental procedure for synthesis of 6-(4-phenyl-1H-1,2,3- 126.41, 125.93, 125.26, 124.94, 124.70, 121.19, 120.88, 120.40,
triazol-1-yl)benzimidazo[1,2-a]quinoline (4a):
117.53, 114.92, 114.07; HRMS (ESI, m/z): Calcd for C23H16N5 [M+H]+
2-(azidomethyl)-1H-benzo[d]imidazole 1a mmol), 362.1406, found 362.1410.
phenylacetylene 3a (3 mmol), CuSO4.5H2O (0.1 mmol), sodium
(3
ascorbate (0.2 mmol) and t-BuOH:H2O (1:1, 5mL) were added into a 6-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline
10 mL round bottom flask. The reaction mixture was stirred at room (5b)
temperature for 30 min. Reaction progress was monitored by TLC. Beige solid, 342 mg 88%, m.p. 252-253 °C; IR νmax (KBr) 3154, 1541,
1
After completion, the reaction mass was diluted with water (10 mL). 1467, 1398, 1246, 1078, 1018, 813, 754 cm-1; H NMR (400 MHz,
Resultant precipitate was filtered and dried to obtain analytical CDCl3) δ 9.74 (s, 1H), 8.61 (d, J = 9.6 Hz, 2H), 8.44 (d, J = 7.7 Hz, 1H),
1
pure product 4a. colorless solid, 775 mg 94%, m.p. 209-210 °C; H 8.10 (dd, J = 7.4, 1.4 Hz, 1H), 7.98 (dd, J = 7.9, 1.4 Hz, 1H), 7.94 (d, J
NMR (400 MHz, DMSO-d6) δ 12.20 (s, 1H), 8.05 (s, 1H), 7.79-7.77 (d, = 8.1 Hz, 2H), 7.83 – 7.79 (ddd, J = 8.5, 7.3, 1.5 Hz, 1H), 7.63 – 7.53
J = 7.8 Hz, 3H), 7.42-7.38 (t, J = 7.5 Hz, 2H), 7.36-7.29 (m, 2H), 7.27- (m, 3H), 7.34 – 7.29 (m, 2H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3)
7.25 (dd, J = 5.8, 2.8 Hz, 2H), 5.89 (s, 2H); 13C NMR (100 MHz, δ 147.82, 144.24, 141.58, 138.11, 134.60, 131.24, 130.46, 130.31,
DMSO-d6) δ 147.96, 130.24, 128.70, 128.10, 125.52, 120.44, 48.03; 129.54, 127.71, 125.97, 125.12, 124.97, 124.93, 123.74, 122.20,
HRMS (ESI, m/z): Calcd for C16H14N5 [M+H]+ 276.1249, found 121.49, 121.13, 121.02, 115.06, 114.15, 21.38; HRMS (ESI, m/z):
276.1251.
Calcd for C24H18N5 [M+H]+ 376.1562, found 376.1569.
3. Experimental procedure for synthesis of 6-(4-phenyl-1H-1,2,3- 6-(4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
triazol-1-yl)benzimidazo[1,2-a]quinoline (5a): a]quinoline (5c)
An oven dried 10 mL round bottom flask was charged with 2- Beige solid, 249 mg 72%, m.p. 216-217 °C; IR νmax (KBr) 3055, 1541,
1
(azidomethyl)-1H-benzo[d]imidazole
1a
(1
mmol),
2- 1467, 1395, 1245, 1199, 1075, 1015, 821, 754 cm-1; H NMR (400
bromobenzaldehyde 2a (1 mmol), phenylacetylene 3a (1 mmol), MHz, CDCl3) δ 9.77 (s, 1H), 8.63 (d, J = 7.6 Hz, 2H), 8.45 (d, J = 7.6
K2CO3 (3 mmol), CuI (0.1 mmol), picolinic acid (0.2 mmol) and PEG- Hz, 1H), 8.11 (m, 1H), 7.99 (dd, J = 7.4, 2.9 Hz, 3H), 7.84 – 7.78 (m,
400 (2 mL). The resulting mixture was stirred at 120 °C under N2 1H), 7.63 – 7.53 (m, 5H), 1.40 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
atmosphere. Reaction progress was monitored by TLC. After 151.35, 147.66, 144.12, 141.37, 134.41, 131.07, 130.30, 130.18,
completion, the reaction mass was allowed to cool to ambient 127.73, 125.81, 125.78, 125.03, 124.85, 124.75, 123.66, 122.06,
temperature, diluted with water (5 mL) and extracted with DCM (3 121.57, 121.02, 120.72, 114.90, 114.04, 34.74, 31.37; HRMS (ESI,
× 5 mL). The combined organic layer was dried with anhydrous m/z): Calcd for C27H24N5 [M+H]+ 418.2032, found 418.2028.
Na2SO4 and evaporated to dryness. The crude material was purified
by column chromatography using eluent (CHCl3/EtOAc = 50/1) to 6-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
obtain desired tandem product 5a in 93% yield (335 mg). The a]quinoline (5d)
compounds 5b-g and 5k-u were prepared following the same Beige solid, 281 mg 72%, m.p. 215-216 °C; IR νmax (KBr) 3051, 1563,
protocol.
1498, 1465, 1247, 1022, 818, 754 cm-1; 1H NMR (400 MHz, CDCl3) δ
9.71 (s, 1H), 8.64 (d, J = 8.5 Hz, 1H), 8.61 (s, 1H), 8.47 (d, J = 7.6 Hz,
1H), 8.11 (d, J = 7.1 Hz, 1H), 8.02 - 7.97 (m, 3H), 7.85 – 7.81 (t, J =
4. Experimental procedure for synthesis of 5h-j:
An oven dried 10 mL round bottom flask was charged with 2- 7.9 Hz, 1H), 7.65 – 7.55 (m, 3H), 7.05 (d, J = 9.6 Hz, 2H), 3.89 (s, 3H);
(azidomethyl)-1H-benzo[d]imidazole 1a (1 mmol), 2-bromo 13C NMR (100 MHz, CDCl3) δ 159.78, 147.60, 144.26, 141.52, 134.69,
benzaldehyde 2a (1 mmol), low boiling substituted acetylene 3h-j 131.21, 130.43, 130.24, 127.36, 125.11, 124.95, 124.91, 123.73,
(1 mmol), K2CO3 (3 mmol), CuI (0.1 mmol), picolinic acid (0.2 mmol) 123.25, 122.18, 121.09, 121.00, 120.97, 115.04, 114.26, 114.15,
and PEG-400 (2 mL). The resulting mixture was stirred under N2 55.37; HRMS (ESI, m/z): Calcd for C24H18N5O [M+H]+ 392.1511,
atmosphere at 50 ºC for 1 h before elevating the operating found 392.1516.
temperature to 120 ºC for 8 h. Reaction progress was monitored by
TLC. After completion, the reaction mass was allowed to cool to 6-(4-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
ambient temperature, diluted with water (5 mL) and extracted with a]quinoline (5e)
DCM (3 × 5 mL). The combined organic layer was dried with Colorless solid, 296 mg 81%, m.p. 278-279 °C; IR νmax (KBr) 3046,
1
anhydrous Na2SO4 and evaporated to dryness. The crude material 1542, 1468, 1247, 1198, 1017, 821, 754 cm-1; H NMR (400 MHz,
was purified by column chromatography using eluent (CHCl3/EtOAc CDCl3) δ 9.84 (s, 1H), 8.76 – 8.64 (m, 2H), 8.51 (d, J = 6.8 Hz, 1H),
= 50/1) to obtain desired tandem product 5h-j.
8.14 (d, J = 7.2 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 8.01 (d, J = 8.4 Hz,
2H), 7.89 – 7.85 (t, J = 6.7 Hz, 1H), 7.65 – 7.59 (dd, J = 14.5, 7.0 Hz,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 8 of 12
ARTICLE
Journal Name
3H), 7.48 (d, J = 8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 146.68, 6-(1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5j)
View Article Online
136.22, 134.42, 133.31, 132.37, 132.10, 130.91, 128.37, 128.32, Pale yellow solid, 242 mg 88%, m.p. 212-21D3O°IC: ;10IR.10ν3m9a/xC(5KRBAr2)43004589D,
1
128.10, 127.53, 127.37, 126.27, 125.47, 121.69, 119.64, 118.91, 1544, 1466, 1395, 1252, 1216, 1078, 1010, 737 cm-1; H NMR (400
115.76, 115.64, 115.03; HRMS (ESI, m/z): Calcd for C23H15ClN5 MHz, CDCl3) δ 9.59 (s, 1H), 8.68 (d, J = 8.5 Hz, 1H), 8.62 (s, 1H), 8.51
[M+H]+ 396.1016, found 396.1021.
– 8.48 (dd, J = 7.1, 1.8 Hz, 1H), 8.11 – 8.08 (dd, J = 7.0, 2.2 Hz, 1H),
8.04 – 8.01 (dd, J = 7.9, 1.2 Hz, 1H), 7.98 (d, J = 1.1 Hz, 1H), 7.88 –
7.83 (m, 1H), 7.64 – 7.58 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
144.19, 141.58, 134.57, 133.81, 131.17, 130.42, 130.38, 125.98,
6-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]
quinoline (5f)
Beige solid, 330 mg 87%, m.p. 292-293 °C; IR νmax (KBr) 3052, 1562, 125.12, 124.96, 123.75, 122.08, 121.34, 121.07, 115.02, 114.11;
1495, 1400, 1226, 1019, 827, 754 cm-1; 1H NMR (400 MHz, CDCl3) δ HRMS (ESI, m/z): Calcd for C17H12N5 [M+H]+ 286.1093, found
9.81 (s, 1H), 8.70 (d, J = 8.6 Hz, 1H), 8.67 (s, 1H), 8.52 (d, J = 7.5 Hz, 286.1097.
1H), 8.14 (d, J = 8.9 Hz, 1H), 8.08 – 8.02 (m, 3H), 7.87 (t, J = 7.9 Hz,
1H), 7.68 – 7.58 (m, 3H), 7.23 – 7.18 (t, J = 8.7 Hz, 2H); 13C NMR (100 (1-(benzimidazo[1,2-a]quinolin-6-yl)-1H-1,2,3-triazol-4-yl)
1
MHz, CDCl3) δ 162.06 (d, JCF = 250.48 Hz), 147.70, 138.29, 135.62, methanol (5k)
3
133.64, 133.46, 131.69, 129.50, 128.50, 127.98 (d, JCF = 9.09 Hz), Beige solid, 210 mg 67%, m.p. 236-237 °C; IR νmax (KBr) 3302, 3074,
127.85, 127.77, 126.60, 124.44, 122.50, 120.85, 117.45, 116.39, 1540, 1401, 1202, 1039, 848, 756 cm-1; 1H NMR (400 MHz, CDCl3) δ
2
116.17 (d, JCF = 25.25 Hz), 115.61; HRMS (ESI, m/z): Calcd for 9.55 (s, 1H), 8.69 (d, J = 8.5 Hz, 1H), 8.60 (s, 1H), 8.50 (d, J = 8.5 Hz,
C23H15FN5 [M+H]+ 380.1311, found 380.1315.
1H), 8.10 (d, J = 7.6 Hz, 1H), 8.03 (d, J = 7.7 Hz, 1H), 7.89 - 7.85 (t, J =
7.9 Hz, 1H), 7.69 – 7.55 (m, 3H), 5.01 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 161.32, 147.32, 139.98, 134.10, 132.70, 131.31, 130.14,
127.25, 127.07, 126.78, 126.26, 125.56, 124.64, 122.12, 118.79,
6-(4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-
yl)benzimidazo[1,2-a]quinoline (5g)
Colorless solid, 344 mg 80%, m.p. 283-284 °C; IR νmax (KBr) 3054, 115.94, 114.94, 55.00; HRMS (ESI, m/z): Calcd for C18H14N5O [M+H]+
1620, 1541, 1397, 1254, 1114, 1015, 826, 754 cm-1; H NMR (400 316.1198, found 316.1195.
1
MHz, CDCl3) δ 9.89 (s, 1H), 8.65 (d, J = 8.8 Hz, 2H), 8.46 (d, J = 7.7
Hz, 1H), 8.13 (d, J = 7.8 Hz, 2H), 8.09 (d, J = 5.9 Hz, 1H), 8.01 (d, J = 6-(4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl)benzoimidazo[1,2-
1.2 Hz, 1H), 7.84 – 7.80 (m, 1H), 7.70 (d, J = 8.2 Hz, 2H), 7.59 – 7.54 a]quinoline (5l)
(m, 3H); 13C NMR (100 MHz, CDCl3) δ 188.9, 163.9, 132.3, 131.0, Beige solid, 239 mg 66%, m.p. 248-249 °C; IR νmax (KBr) 3048, 1599,
129.7, 128.9, 127.2, 126.5, 125.4, 123.8, 122.5, 121.1, 114.0, 55.6; 1545, 1470, 1399, 1213, 1020, 789, 757, 733 cm-1; 1H NMR (400
HRMS (ESI, m/z): Calcd for C24H15F3N5 [M+H]+ 430.1280, found MHz, CDCl3) δ 10.12 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (d, J = 8.6
430.1278.
Hz, 1H), 8.63 (s, 1H), 8.47 (d, J = 7.6 Hz, 1H), 8.32 (d, J = 7.9 Hz, 1H),
8.13 (d, J = 7.5 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.90 – 7.81 (m, 2H),
6-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline 7.64 – 7.57 (m, 3H), 7.34 – 7.31 (m, 1H); 13C NMR (100 MHz, CDCl3)
(5h)
δ 145.49, 143.82, 143.48, 134.22, 133.39, 131.74, 130.04, 128.60,
Pale green solid, 249 mg 77%, m.p. 194-195 °C; IR νmax (KBr) 3081, 127.80, 127.24, 126.69, 126.02, 125.88, 124.32, 122.21, 121.58,
1540, 1397, 1243, 1027, 893, 813, 754 cm-1; 1H NMR (400 MHz, 118.38, 116.21, 115.22; HRMS (ESI, m/z): Calcd for C22H15N6 [M+H]+
CDCl3) δ 9.20 (s, 1H), 8.62 (d, J = 8.5 Hz, 1H), 8.52 (s, 1H), 8.45 (dd, J 363.1358, found 363.1362.
= 7.4, 1.4 Hz, 1H), 8.09 (dd, J = 7.2, 1.6 Hz, 1H), 8.00-7.95 (m, 1H),
7.84 – 7.77 (m, 1H), 7.63 – 7.54 (m, 3H), 2.20 – 2.11 (m, 1H), 1.08 – 3-methoxy-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
1.04 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 149.08, 143.12, 140.58, a]quinoline (5m)
133.38, 130.08, 129.22, 129.07, 123.97, 123.80, 122.59, 121.11, Pale green solid, 250 mg 64%, m.p. 254-255 °C; IR νmax (KBr) 3061,
119.97, 119.84, 113.89, 113.02, 6.75, 5.89; HRMS (ESI, m/z): Calcd 1539, 1482, 1454, 1404, 1236, 1019, 806, 768, 739, 694 cm-1; 1H
for C20H16N5 [M+H]+ 326.1406, found 326.1402.
NMR (400 MHz, CDCl3) δ 9.84 (s, 1H), 8.57 (s, 1H), 8.53 (d, J = 8.9 Hz,
1H), 8.40 (d, J = 8.1 Hz, 1H), 8.13 – 8.05 (m, 3H), 7.64 – 7.51 (m, 4H),
7.45 – 7.36 (m, 3H), 3.98 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
6-(4-butyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5i)
Colorless solid, 242 mg 71%, m.p. 130-131 °C; IR νmax (KBr) 3052, 157.98, 148.26, 137.29, 136.14, 129.32, 129.20, 129.07, 128.10,
1539, 1453, 1399, 1224, 1035, 889, 814, 756, cm-1; 1H NMR (400 128.00, 127.73, 126.28, 126.02, 125.87, 123.88, 122.63, 121.23,
MHz, CDCl3) δ 9.25 (s, 1H), 8.62 (d, J = 8.5 Hz, 1H), 8.54 (s, 1H), 8.45 120.78, 117.57, 117.41, 115.13, 111.66, 55.99; HRMS (ESI, m/z):
(d, J = 8.2 Hz, 1H), 8.11 – 8.06 (m, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.84 – Calcd for C24H18N5O [M+H]+ 392.1511, found 392.1509.
7.78 (m, 1H), 7.63 – 7.53 (m, 3H), 2.95 – 2.89 (m, 2H), 1.88 – 1.80
(dt, J = 13.0, 7.6 Hz, 2H), 1.55 – 1.45 (m, 2H), 1.03 – 0.99 (t, J = 7.4 2,3-dimethoxy-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.43, 144.19, 141.70, a]quinoline (5n)
134.45, 131.16, 130.30, 130.14, 125.09, 125.03, 124.89, 123.65, Beige solid, 321 mg 76%, m.p. 280-281 °C; IR νmax (KBr) 3064, 1536,
122.97, 122.21, 121.03, 120.95, 114.97, 114.11, 31.59, 25.58, 22.50, 1468, 1389, 1270, 1017, 759 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.74
13.93; HRMS (ESI, m/z): Calcd for C21H20N5 [M+H]+ 342.1719, found (s, 1H), 8.46 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08 – 8.04 (td, J = 7.9,
342.1721.
0.9 Hz, 3H), 7.93 (s, 1H), 7.63 – 7.57 (m, 1H), 7.54 – 7.49 (td, J = 8.1,
4.8 Hz, 3H), 7.43 – 7.37 (m, 1H), 7.21 (s, 1H), 4.14 (s, 3H), 4.00 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 153.91, 148.38, 147.43, 136.16,
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 12
RSC Advances
Please do not adjust margins
Journal Name
ARTICLE
133.72, 128.43, 128.30, 128.15, 127.73, 127.11, 126.36, 125.05, 9-methyl-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidaVzioew[1A,r2ti-cle Online
DOI: 10.1039/C5RA24048D
10-methyl-6-(4-phenyl-1H-1,2,3-triazol-1-
124.97, 119.62, 117.08, 116.27, 115.91, 114.23, 109.25, 97.23, a]quinoline
and
55.95, 55.55; HRMS (ESI, m/z): Calcd for C25H20N5O2 [M+H]+ yl)benzimidazo[1,2-a]quinoline (5s)
422.1617, found 422.1620.
(for regioisomeric mixture = 1:1) Beige solid, 315 mg 84%, m.p. 242-
243 °C; IR νmax (KBr) 3055, 1539, 1469, 1396, 1199, 1014, 766, 692
1
3-chloro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
a]quinoline (5o)
cm-1; H NMR (400 MHz, CDCl3) δ 9.83 (s, 0.5H), 9.81 (s, 0.5H), 8.66
– 8.58 (m, 2H), 8.32 (d, J = 8.6 Hz, 0.5H), 8.25 (s, 0.5H), 8.11 – 8.06
Beige solid, 237 mg 60%, m.p. 271-272 °C; IR νmax (KBr) 3058, 1535, (m, 2H), 8.04 – 7.97 (m, 1.5H), 7.90 (s, 0.5H), 7.83 (m, 1H), 7.61 –
1448, 1402, 1205, 1015, 796, 738, 688 cm-1; 1H NMR (400 MHz, 7.50 (m, 3H), 7.47 – 7.38 (m, 2H), 2.71 (s, 1.5H), 2.63 (s, 1.5H); 13C
CDCl3) δ 9.83 (s, 1H), 8.57 (d, J = 7.7 Hz, 2H), 8.39 (m, 1H), 8.12 (m, NMR (100 MHz, CDCl3) δ 148.13, 148.04, 138.22, 136.11, 133.84,
1H), 8.06 (dd, J = 5.2, 3.2 Hz, 2H), 7.97 (d, J = 2.4 Hz, 1H), 7.78 – 7.75 133.55, 132.60, 132.30, 131.18, 131.10, 130.27, 129.19, 129.14,
(dd, J = 9.1, 2.4 Hz, 1H), 7.66 – 7.57 (m, 2H), 7.55 – 7.49 (m, 2H), 129.09, 128.78, 128.55, 128.45, 127.92, 127.34, 126.81, 126.58,
7.44 – 7.38 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 148.05, 140.58, 125.99, 125.87, 125.38, 122.09, 121.80, 121.46, 121.28, 118.14,
139.88, 132.41, 131.87, 131.80, 130.22, 129.83, 129.17, 129.11, 117.81, 115.84, 114.62, 114.51, 22.27, 21.60; HRMS (ESI, m/z):
128.60, 126.82, 126.06, 125.37, 123.89, 123.52, 123.29, 121.84, Calcd for C24H18N5 [M+H]+ 376.1562, found 376.1565.
119.69, 116.96, 114.46; HRMS (ESI, m/z): Calcd for C23H15ClN5
[M+H]+ 396.1016, found 396.1014.
9-chloro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
a]quinoline and 10-chloro-6-(4-phenyl-1H-1,2,3-triazol-1-
3-fluoro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
a]quinoline (5p)
yl)benzimidazo[1,2-a]quinoline (5t)
(for regioisomeric mixture = 1:1) Off white solid, 304 mg 77%, m.p.
Pale green solid, 337 mg 89%, m.p. 312-313 °C; IR νmax (KBr) 3032, 278-279 °C; IR νmax (KBr) 3057, 1539, 1395, 1201, 1017, 765 cm-1; 1H
1
1539, 1451, 1402, 1203, 1013, 916, 760 cm-1; H NMR (400 MHz, NMR (400 MHz, CDCl3) δ 9.75 (s, 0.5H), 9.74 (s, 0.5H), 8.67 (s, 0.5H),
CDCl3) δ 8.99 (s, 1H), 8.91 (s, 1H), 8.89 (d, J = 3.9 Hz, 1H), 8.65 (d, J = 8.65 (s, 0.5H), 8.54 (dd, J = 16.8, 8.5 Hz, 1H), 8.45 (d, J = 1.7 Hz,
8.4 Hz, 1H), 8.13 (d, J = 7.7 Hz, 1H), 7.94 – 7.81 (m, 4H), 7.73 – 7.65 0.5H), 8.37 (d, J = 8.9 Hz, 0.5H), 8.09 – 8.00 (m, 4H), 7.85 (dd, J =
(m, 2H), 7.39 – 7.30 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 158.38 (d, 14.0, 6.6 Hz, 1H), 7.64 – 7.57 (m, 1.5H), 7.56 – 7.48 (m, 2.5H), 7.41
1JCF = 252.5 Hz), 147.87, 136.17, 132.97, 128.85, 128.79, 128.31, (t, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 148.55, 148.52,
3
128.18, 126.86, 126.40, 126.07, 125.13, 123.48 (d, JCF = 9.09 Hz), 138.97, 138.93, 134.51, 134.46, 134.43, 133.96, 133.85, 133.13,
121.30 (d, 2JCF = 26.26 Hz), 120.36, 119.74, 118.09 (d, 3JCF = 9.09 Hz), 133.10, 132.34, 131.75, 129.82, 129.63, 129.22, 129.09, 128.14,
2
116.05, 115.49 (d, JCF = 24.24 Hz), 114.74; HRMS (ESI, m/z): Calcd 128.07, 127.85, 127.04, 126.02, 122.48, 122.44, 121.02, 120.93,
for C23H15FN5 [M+H]+ 380.1311, found 380.1314.
120.80, 120.61, 118.35, 118.33, 116.99, 116.63, 116.31, 116.27,
115.60; HRMS (ESI, m/z): Calcd for C23H15ClN5 [M+H]+ 396.1016,
found 396.1019.
6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5q)
Colorless solid, 293 mg 81%, m.p. 315-316 °C; IR νmax (KBr) 3050,
1530, 1449, 1200, 1014, 903, 766 cm-1; 1H NMR (400 MHz, CDCl3) δ 9-fluoro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-
9.55 (d, J = 8.0 Hz, 1H), 9.22 (d, J = 3.2 Hz, 1H), 9.14 (s, 1H), 9.11 (s, a]quinoline
and
10-fluoro-6-(4-phenyl-1H-1,2,3-triazol-1-
1H), 8.77 (d, J = 7.2 Hz, 1H), 8.13 (d, J = 7.8 Hz, 1H), 7.99 – 7.86 (m, yl)benzimidazo[1,2-a]quinoline (5u)
3H), 7.66 – 7.54 (m, 2H), 7.19 (d, J = 3.8 Hz, 3H); 13C NMR (100 MHz, (for regioisomeric mixture = 1:1) Colorless solid, 250 mg 66%, m.p.
CDCl3) δ 152.24, 147.85, 142.97, 138.87, 136.46, 132.54, 128.72, 266-267 °C; IR νmax (KBr) 3035, 1541, 1476, 1398, 1203, 1016, 762,
1
128.56, 128.21, 127.85, 126.80, 126.49, 125.25, 125.06, 123.21, 692 cm-1; H NMR (400 MHz, CDCl3) δ 9.77 (s, 0.5H), 9.76 (s, 0.5H),
120.12, 119.54, 118.24, 116.67, 114.92; HRMS (ESI, m/z): Calcd for 8.68 (s, 0.5H), 8.63 (s, 0.5H), 8.60 (d, J = 8.5 Hz, 0.5H), 8.49 (d, J =
C22H15N6 [M+H]+ 363.1358, found 363.1355.
8.5 Hz, 0.5H), 8.42 (dd, J = 9.2, 4.4 Hz, 0.5H), 8.17 (dd, J = 9.6, 2.3
Hz, 0.5H), 8.08 – 8.01 (m, 3.5H), 7.88 – 7.83 (m, 1H), 7.76 (dd, J =
9.0, 2.5 Hz, 0.5H), 7.61 (t, J = 7.6 Hz, 1H), 7.51 (td, J = 7.6, 1.5 Hz,
1
12-methyl-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzo[g]benzimidazo
[1,2-a][1,8]naphthyridine (5r)
2H), 7.43 – 7.31 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 160 (d, JCF
=
1
253.51 Hz), 158.98 (d, JCF = 245.43 Hz), 147.54, 140.85, 140.67,
Green solid, 255 mg 60%, m.p. 316-317 °C; IR νmax (KBr) 3045, 1610, 135.95, 133.68, 133.62, 132.81, 132.54, 131.34, 131.29, 129.96,
1534, 1476, 1402, 1208, 1015, 765 cm-1; 1H NMR (400 MHz, CDCl3) δ 129.84, 129.34, 129.31, 129.16, 128.34, 128.29, 126.96, 126.87,
9.74 (d, J = 7.2 Hz, 1H), 9.26 (s, 1H), 9.19 (s, 1H), 9.14 (s, 1H), 8.15 126.78, 126.33, 126.04, 122.42, 122.08, 122.03, 121.68, 121.61,
(d, J = 6.8 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.98 – 7.94 (m, 3H), 7.79 – 120.03, 119.93, 116.18, 116.07, 115.92, 115.66, 115.58, 115.50,
7.72 (m, 3H), 7.50-7.44 (m, 3H), 3.06 (s, 3H); 13C NMR (100 MHz, 114.21, 113.96, 104.84, 104.56, 102.19, 101.89; HRMS (ESI, m/z):
CDCl3) δ 148.58, 147.27, 141.43, 140.95, 138.17, 136.61, 134.17, Calcd for C23H15FN5 [M+H]+ 380.1311, found 380.1315.
134.06, 129.64, 129.17, 129.00, 128.75, 128.09, 127.69, 127.55,
126.91, 126.86, 125.94, 120.46, 120.21, 118.20, 116.36, 115.22,
18.66; HRMS (ESI, m/z): Calcd for C27H19N6 [M+H]+ 427.1671, found
427.1676.
Spectral properties
The absorption and fluorescence spectra of all compounds in liquid
solutions of CHCl3 (spectroscopic grade) at room temperature were
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 10 of 12
ARTICLE
Journal Name
recorded with the aid of a Jasco V-650 spectrophotometer and
Jasco FP-6300 spectrofluorometer, respectively. Fluorescence
quantum yield (Øfluo) was determined using quinine sulphate in
0.1M H2SO4 as a standard (Øfluo = 0.54).
8
9
(a) C.-Y. Wang, J.-F. Zou, Z.-J. Zheng, W.-S. Huang,VLi.ewLiA,rLti.c-lWe O.nXlinue,
RSC Adv., 2014, 4, 54256; (b) S. Ast, TD. OFiIs:c1h0e.1r0,3H9/.CM5RuAl2le4r0,4W8D.
Mickler, M. Schwichtenberg, K. Rurack, H.-J. Holdt, Chem. Eur. J.
2013, 19, 2990; (c) G. Agalave, S. R. Maujan, V. S. Pore, Chem.
Asian J., 2011, 6, 2696; (d) K. Sivakumar, F. Xie, B. M. Cash, S.
Long, H. N. Barnhill, W. Qian, Org. Lett., 2004, 6, 4603.
(a) N. Perin, R. Nhili, K. Ester, W. Laine, G. Karminski-Zamola, M.
Kralj, M.-H. D. Cordonnier,; M. Hranjec, Eur. J. Med. Chem.,
2014, 80, 218; (b) N. Perin, L. Uzelac, I. Piantanida, G. Karminski-
Zamola, M. Kralj, M. Hranjec, Biorg. Med. Chem., 2011, 19,
6329; (c) M. Hranjec, E. Horak, M. Tireli, G. Pavlovic, G.
Karminski-Zamola, Dyes Pigm. 2012, 95, 644; (d) N. Perin, M.
Hranjec, G. Pavlovic, G. Karminski-Zamola, Dyes Pigm. 2011, 91,
79; (e) M. Hranjec, G. Pavlovic, M. Marjanovic, M. Kralj, G.
Karminski-Zamola, Eur. J. Med. Chem., 2010, 45, 2405; (f) M.
Hranjec, B. Lucic, I. Ratkaj, S. K. Pavelic, I. Piantanida, K. Pavelic,
G. Karminski-Zamola, Eur. J. Med. Chem., 2011, 46, 2748; (g) M.
Hranjec, M. Kralj, I. Piantanida, M. Sedic, L. Suman, K. Pavelic, G.
Karminski-Zamola, J. Med. Chem., 2007, 50, 5696.
Acknowledgements
KVGCS thanks DBT, New Delhi [No. BT/PR4801/MED/29/370/2012]
for providing financial support. HNN is grateful to BITS-Pilani,
Hyderabad Campus for providing institute fellowship. AS thanks
DBT for junior research fellowship. NS thanks UGC for senior
research fellowship.
Notes and references
1
2
D. B. Ramachary, S. Jain, Org. Biomol. Chem., 2011, 9, 1277.
(a) F. Lorenzini, J. Tjutrins, J. S. Quesnel, B. A. Arndtsen, in
Metal-Catalyzed Multicomponent Synthesis of Heterocycles,
eds J. Zhu, Q. Wang and M.-X. Wang, Wiley-VCH Verlag GmbH &
Co. KGaA, Weinheim, Germany, 2014, ch. 08, pp. 207; (b) G.
Balme, D. Bouyssi, N. Monteiro, in Multicomponent Reactions,
eds J. Zhu and H. Bienaymé, Wiley-VCH Verlag GmbH & Co.
KGaA, Weinheim, FRG, 2005, ch. 08, pp. 224.
10 (a) Q. Cai, Z. Li, J. Wei, L. Fu, C. Ha, D. Pei, K. Ding, Org. Lett.,
2010, 12, 1500; (b) J.-Y. Kato, H. Aoyama, T. Yokomatsu, Org.
Biomol. Chem., 2013, 11, 1171; (c) J.-Y. Kato, Y. Ito, R. Ijuin, H.
Aoyama, T. Yokomatsu, Org. Lett., 2013, 15, 3794; (d) J.-Y. Kato,
R. Ijuin, H. Aoyama, T. Yokomatsu, Tetrahedron, 2014, 70, 2766.
11 (a) O. V. Khilya, T. A. Volovnenko, A. V. Turov, Y. M. Volovenko,
Chem. Heterocycl. Compd., 2004, 40, 1063; (b) M. Hranjec, G.
Karminski-Zamola, Molecules, 2007, 12, 1817; (c) C. Venkatesh,
G. S. M. Sundaram, H. Ila, H. Junjappa, J. Org. Chem., 2006, 71,
1280; (d) H. Wang, Y. Wang, C. Peng, J. Zhang, Q. Zhu, J. Am.
Chem. Soc., 2010, 132, 13217; (e) K. S. Masters, T. R. M. Rauws,
A. K. Yadav, W. A. Herrebout, B. Vander Veken, B. U. W. Maes,
Chem. Eur. J., 2011, 17, 6315; (f) B.-W. Zhou, J. R. Gao, D. Jiang,
J. H. Jia, Z. P. Yang, H. W. Jin, Synthesis, 2010, 2794.
12 (a) W. Qian, A. Amegadzie, D. Winternheimer, J. Allen, Org.
Lett., 2013, 15, 2986; (b) W. Qian, H. Wang, J. Allen, Angew.
Chem. Int. Ed., 2013, 52, 10992.
13 (a) M. M. Yu, Z. X. Li, L. H. Wei, D. H. Wei, M. S. Tang, Org.
Lett., 2008, 10, 5115; (b) F. M. Antonio, M. Q. José, P. Carlos,
New J. Chem., 2012, 36, 1634; (c) V. Lucchesi, P. H. Dow, D. M.
Shore, S. Bertini, B. M. Ehrmann, M. Allarà, L. Lawrence, A.
Ligresti, F. Minutolo, G. Saccomanni, H. Sharir, M. Macchia, V. D.
Marzo, M. E. Abood, P. H. Reggio, C. Manera, J. Med.
Chem., 2014, 57, 8777.
14 (a) M. P. Drapeau, T. Ollevier, M. Taillefer, Chem. Eur. J., 2014,
20, 5231; (b) O. Obulesu, N. Jagadeesh Babu, S. Suresh, Org.
Biomol. Chem., 2015, 13, 8232.
15 (a) A. K. Verma, J. Singh, V. K. Sankar, R. Chaudhary, R. Chandra,
Tetrahedron Lett., 2007, 48, 4207; (b) A. K. Verma, J. Singh, R.
Chaudhary, Tetrahedron Lett., 2007, 48, 7199; (c) A. K. Verma, J.
Singh, R. C. Larock, Tetrahedron, 2009, 65, 8434; (d) A. K.
Verma, R. R. Jha, R. Chaudhary, R. K. Tiwari, K. S. K. Reddy, A.
Danodia, J. Org. Chem., 2012, 77, 8191.
16 (a) C. Wang, S. Li, H. Liu, Y. Jiang, H. Fu, J. Org. Chem., 2010, 75,
7936; (b) H. Chai, J. Li, L. Yang, H. Lu, Z. Qi, D. Shi, RSC Adv.,
2014, 4, 44811.
17 J.-J. Shie, Y.-C. Liu, Y.-M. Lee, C. Lim, J.-M. Fang, C.-H. Wong, J.
Am. Chem. Soc., 2014, 28, 9953.
3
Click followed by inter/intramolecular arylation of 1,2,3-triazole
C5-H or N-C bond formation: (a) K. Pericherla, A. Jha, B.
Khungar, A. Kumar, Org. Lett., 2013, 15, 4304; (b) D. K. Barange,
Y.-C. Tu, V. Kavala, C.-W. Kuo, C.-F. Yaoa, Adv. Synth. Catal.,
2011, 353, 41; (c) L. Ackermann, H. K. Potukuchi, D. Landsberg,
R. Vicente, Org. Lett., 2008, 10, 3081; (d) Q. Cai, J. Yan, K. Ding,
Org. Lett., 2012, 14, 3332; (e) A. S. Reddy, M. N. Reddy, K. C. K.
Swamy, RSC Adv., 2014, 4, 28359; (f) M. N. Reddy, K. C. K.
Swamy, Eur. J. Org. Chem., 2012, 2012, 2013; (g) J. Yan, F. Zhou,
D. Qin, T. Cai, K. Ding, Q. Cai, Org. Lett., 2012, 14, 1262; (h) Y.-Y.
Hu, J. Hu, X.-C. Wang, L.-N. Guo, X.-Z. Shu, Y.-N. Niu, Y.-M. Liang,
Tetrahedron, 2010, 66, 80; (i) K. Brahma, B. Achari, C.
Chowdhury, Synthesis, 2013, 45, 545; (j) W. Chen, H. Li, X. Gu, Y.
Zhu, Synlett, 2015, 26, 785.
4
M. N. Reddy, K. C. K. Swamy, Org. Biomol. Chem., 2013, 11,
7350.
5
6
7
J.-W. Sun, X.-S. Wang, Y. Liu, J. Org. Chem., 2013, 78, 10560.
A. B. Pawar, S. Chang, Chem. Commun., 2014, 50, 448.
(a) C. Testa, M. Scrima, M. Grimaldi, A. M. D’Ursi, M. L. Dirain,
N. Lubin-Germain, A. Singh, C. Haskell-Luevano, M. Chorev, P.
Rovero, A. M. Papini, J. Med. Chem., 2014, 57, 9424; (b) T. S.
Dexheimer, A. S. Rosenthal, D. K. Luci, Q. Liang, M. A. Villamil, J.
Chen, H. Sun, E. H. Kerns, A. Simeonov, A. Jadhav, Z. Zhuang, D.
J. Maloney, J. Med. Chem., 2014, 57, 8099; (c) S. Zhou, H. Liao,
M. Liu, G. Feng, B. Fu, R. Li, M. Cheng, Y. Zhao, P. Gong, Biorg.
Med. Chem., 2014, 22, 6438; (d) M. F. Mady, G. E. A. Awad, K. B.
Jørgensen, Eur. J. Med. Chem., 2014, 84, 433; (e) B. D. Bala, S.
Muthusaravanan, T. S. Choon, M. A. Ali, S. Perumal, Eur. J. Med.
Chem., 2014, 85, 737; (f) S. Sinn, B. Schulze, C. Friebe, D.
G. Brown, M. Jäger, E.Altuntaş, J. Kübel, O. Guntner, C.
P. Berlinguette, B. Dietzek, U. S. Schubert, Inorg. Chem., 2014,
53, 2083.
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 11 of 12
RSC Advances
Please do not adjust margins
Journal Name
ARTICLE
18 N. A. Danilkina, P. S. Vlasov, S. M. Vodianik, A. A. Kruchinin, Y. G.
Vlasov, I. A. Balova, Beilstein J. Org. Chem., 2015, 11, 373.
19 J. Hou, Z. Li, Q. Fang, C. Feng, H. Zhang, W. Guo, H. Wang, G. Gu,
Y. Tian, P. Liu, R. Liu, J. Lin, Y.–K. Shi, Z. Yin, J. Shen, P. G. Wang,
J. Med. Chem., 2012, 55, 3066.
View Article Online
DOI: 10.1039/C5RA24048D
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 11
Please do not adjust margins

RSC Advances
Page 12 of 12
View Article Online
DOI: 10.1039/C5RA24048D
102x46mm (300 x 300 DPI)