Sequential Organocatalytic Synthesis of [1,2,3]Triazolo[1,5-a]quinolines

Article abstract of DOI:10.1002/adsc.202000887

In this work, a one-pot sequential organocatalytic method for the synthesis of fused [1,2,3]triazolo[1,5-a]quinolines through successive cyclization and condensation is presented. In this synthetic strategy, the intermolecular [3+2]-cycloaddition occurs between 1,3-dicarbonyl compounds and o-carbonyl-substituted phenylazide compounds, for the formation of the 1,2,3-triazole intermediates. Subsequently, an intramolecular condensation reaction generates the fused quinoline ring by the new C?C bond formation, giving the products in yields ranging from moderate to excellent. All the reactions were performed using 20 mol% of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst in the presence of DMSO as solvent at 120 °C for 24 h and tolerate a range of 1,3-dicarbonyl compounds, such as β-keto esters and 1,3-diketones, and o-formyl, o-acetyl or o-benzoyl substituted phenylazide compounds. (Figure presented.).

Full text of DOI:10.1002/adsc.202000887

Title: Sequential Organocatalytic Synthesis of [1,2,3]-triazoyl-[1,5-a]-
quinolines
Authors: Gabriel Costa, Mariana Bach, Maiara de Moraes, Thiago
Barcellos da Silva, Eder Lenardao, Márcio Silva, and Diego
Alves
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000887
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Sequential Organocatalytic Synthesis of [1,2,3]Triazolo[1,5-
a]quinolines
Gabriel P. da Costa,a Mariana F. Bach,a Maiara C. de Moraes,b Thiago Barcellos,b Eder
J. Lenardão,a Márcio S. Silvaa and Diego Alvesa*
a LASOL - CCQFA - Universidade Federal de Pelotas - UFPel - P.O. Box 354 - 96010-900, Pelotas, RS, Brazil.
Phone/fax: +55 53 32757533, e-mail: diego.alves@ufpel.edu.br (D. Alves).
b Laboratory of Biotechnology of Natural and Synthetic Products, Universidade de Caxias do Sul, Caxias do Sul, RS,
Brazil.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. In this work, a one-pot sequential organocatalytic All the reactions were performed using 20 mol% of 1,8-
method for the synthesis of fused [1,2,3]triazolo[1,5- diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst in the
a]quinolines
through
successive
cyclization
and presence of DMSO as solvent at 120 °C for 24 h and
condensation is presented. In this synthetic strategy, the tolerate a range of 1,3-dicarbonyl compounds, such as β-
intermolecular [3+2]-cycloaddition occurs between 1,3- keto esters and 1,3-diketones, and o-formyl, o-acetyl or o-
dicarbonyl
compounds
and
o-carbonyl-substituted benzoyl substituted phenylazide compounds.
phenylazide compounds, for the formation of the 1,2,3-
triazole intermediates. Subsequently, an intramolecular
condensation reaction generates the fused quinoline ring by
the new C-C bond formation, giving the products in yields
ranging from moderate to excellent.
Keywords: Organocatalysis, quinolines, 1,2,3-triazoles.
have prepared compound A (QTC-4-MeOBnE),
which exerts therapeutic effect through multiple
pathways involved in Alzheimer’s disease,[9a] and
Introduction
Heterocycles represent the most general structural compound
B
(QTCA-1),
which
presented
units in several natural and synthetic bioactive anticonvulsant, antinociceptive and anti-inflammatory
compounds.[1] In particular, N-heterocycles are properties,[9b] besides selective cytotoxicity on triple-
unquestionably important since over 60% of the negative breast cancer cells.[9c] Recently, Upadhyay
FDA-approved drugs contain nitrogen heterocycles.[2] and coworkers[10] described the synthesis of a similar
In this sense, 1,2,3-triazoles have attracted significant compound (C, Figure 1) that has the potential to act
interest from synthetic organic chemists in developing as an antileishmanial agent.
new compounds, due to their extensive application in
drug discovery.[3] Efficient methods to access densely
functionalized
1,2,3-triazoles
included
the
organocatalyzed [3+2] cycloaddition reactions[4] via
the generation of enamines, also known as
Ramachary-Bressy-Wang organocatalytic azide-
ketone [3+2]-cycloaddition (OrgAKC),[5] or via
enolates,[6] which act as the dipolarophile partner in
reactions with organic azides.
Quinolines are a class of synthetic and natural-
occurring heterocycles with exciting biological
activities.[7] Compounds containing quinolinic core in
their structure have attracted considerable interest due
to their applications in material science and also due
to the wide range of pharmacologic activities, such as
antimalarial, antioxidant, anxiolytic, and antitumoral
ones.[8] In this context, our group and others have
described the synthesis and pharmacological
Figure 1 Examples of bioactive hybrid molecules
containing triazole and quinoline units.
As demonstrated by several recent reports describing
properties of hybrid molecules containing triazoles the synthesis of triazole-substituted quinolines,[9,10,11]
and quinolines in the structure.[9] As examples, we
the combination of the well-known properties of
1
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
quinolines with those of 1,2,3-triazoles in complex
heterocyclic structures, as [1,2,3]triazolo[1,5-
a]quinolines, has gained significant prominence and
remains the need for further studies. In this regard,
there are several procedures in the literature for the
preparation of these N-containing polycycles, mainly
involving cyclization reactions.[12] Although most of
these methods are very effective, and despite the
significant recent advances, some limitations are still
present, which includes the use of transition metals,
such as Fe,[12c] Cu,[12d-f] or Pd,[12g-i] and require various
reaction steps and complex starting materials, which
are challenging to prepare and environmentally
incompatible.[12j-l]
For instance, in 2014, Liu and coworkers [13] described
a
three-component cascade reaction of cyclic
diaryliodoniums, sodium azide, and terminal alkynes
using copper iodide as catalyst. The synthesis of the
key cyclic diaryl iodoniums, however, involves 3
steps and harsh reaction conditions (Scheme 1, Eq. 1).
In the same year, Hirayama and coworkers[14]
reported the synthesis of several [1,2,3]triazolo[1,5-
a]pyridines and one example of [1,2,3]triazolo[1,5-
a]quinoline. The used methodology involves a
copper(II)-catalyzed oxidative N-N bond formation in
the presence of atmospheric oxygen as the terminal
oxidant, following by a one-pot hydrazonation
(Scheme 1, Eq. 2).
Scheme 1. Examples of synthesis of [1,2,3]-triazolo[1,5-
a]quinolines
Another study was reported by Kumar, in 2016,[15] in
which a palladium-catalyzed domino coupling of 1,4-
disubstituted triazoles was carried out via the
homocondensation with a second molecule, to access
Results and Discussion
different
[1,2,3]triazolo[1,5-f]phenanthridines
(Scheme 1, Eq. 3). More recently, Wu et al.[16] have
prepared [1,2,3]triazolo[1,5-a]pyridines starting from
pyridin-2-ylmethanamines, through an oxidative
catalyst-free N-N coupling strategy. In this report,
only one [1,2,3]triazolo[1,5-a]quinoline was obtained
(Scheme 1, Eq. 4).
Despite the significant advances toward the synthesis
of quinoline-triazole hybrids, the development of
more efficient catalytic processes remains an
important challenge in synthetic organic chemistry.
With the aim to contribute to overcome the current
limitations, we describe herein the organocatalytic
synthesis of several fused [1,2,3]triazolo[1,5-
a]quinolines 3, substituted with ketones or
carboxylate groups, through of a simple and efficient
approach involving o-formyl, o acetyl or o-benzoyl
substituted phenylazides 1 and carbonyl compounds 2,
using DBU (20 mol%) as a catalyst (Scheme 1, Eq. 5).
Initially, we wondered whether 2-azidobenzaldehyde
1a and ethyl acetoacetate 2a could be used as
substrates
for
the
synthesis
of
fused
[1,2,3]triazolo[1,5-a]quinoline 3a, through a cascade
formation of 1,2,3-triazole 4a and intramolecular
condensation reaction, as shown in Scheme 2. The
C(sp3)-H functionalization of 2-methyl azaarenes is
an excellent strategy for the synthesis of new
heterocyclic entities,[17] however this type of reaction
in methyl 1,2,3-triazoles is rare.[18]
Scheme 2. General proposal.
With this strategy in mind, and based in the procedure
already described by Ramachary and coworkers in
2014,[6c] to prepare 1,2,3-triazoles via enolate using
DBU a catalyst, we reacted 2-azidobenzaldehyde 1a
and ethyl acetoacetate 2a in the presence of DBU (10
2
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
peaks. These results are described in the Supporting
Information (Table S1).
mol%) as a catalyst and DMSO as the solvent. After
24 h at room temperature, the only product observed
was the intermediate 4a, obtained in 82% yield,
without the formation of desired product 3a (Table 1,
entry 1).
Focused on obtaining the ethyl[1,2,3]triazolo[1,5-
a]quinoline-3-carboxylate 3a, we evaluated the
influence of temperature, catalyst, and solvent in the
reaction. To our delight, when the temperature was
raised to 70 ºC, the desired product 3a was obtained
in 46% yield, as a mixture with the intermediate 4a,
which was isolated in 30% yield (Table 1, entry 2).
In the absence of the catalyst, only trace amounts of
the product 4a were observed by TLC, and in this
case, the starting materials were recovered (Table 1,
entry 3). Notably, when the reaction was carried out
using diethylamine (10 mol%) as the catalyst, only
the 1,2,3-triazole intermediate 4a was obtained in
80% yield (Table 1, entry 4). In an attempt to examine
the role of the nature of the base (catalyst), different
tertiary amines, such as Et3N, DABCO, DMAP,
N,N-dimethylaniline, and other conventional bases as
K2CO3, Cs2CO3, tBuOK, and KOH were tested as
catalysts. However, none of them proved to be a
catalyst as efficient as DBU, and in all these cases, the
triazole 4a was preferably obtained (Table 1, entries
5-12 vs. entry 2). The increase of the load of DBU
from 10 to 20 mol% caused a small increment in the
yield of 3a (53%) (Table 1, entry 13 vs. entry 2).
Gratifyingly, good results were obtained when the
reactions were performed at 100 ºC and 120 ºC, with
the desired product 3a being isolated in 77% and 92%
yield, respectively (Table 1, entries 14 and 15). Once
the ideal temperature of the reaction was determined
as 120 ºC, we carried out one experiment decreasing
the amount of DBU from 20 to 10 mol%. However,
the reaction was incomplete, and the desired product
3a was obtained in 62% yield (Table 1, entry 16 vs.
entry 15). The desired product 3a was obtained in
63% yield when the reaction was carried out using 20
mol% of KOH as a catalyst, proving that DBU was
the best catalyst for this methodology (Table 1, entry
17 vs. entry 15).
Table 1. Optimization studies to prepare compound 3a.a
Yield (%)b
Catalyst
(mol%)
Temperature
(°C)
Entry
Solvent
3a
4a
1
2
3
4
5
DBU (10)
DBU (10)
-
DMSO
DMSO
DMSO
DMSO
DMSO
25
70
70
70
70
-
46
-
-
82
30
traces
80
Et2NH (10)
Et3N (10)
DABCO
(10)
DMAP
(10)
traces
67
6
7
DMSO
DMSO
70
70
14
9
60
64
N,N-
dimethyl
aniline
(10)
8
DMSO
70
-
28
Further screening of solvents, such as toluene, MeCN,
DMF, and ethylene glycol, showed that the reaction
conducted in DMSO gave a better result (Table 1,
entry 15 vs. entries 18-21). Furthermore, the use of
focused microwave irradiation was evaluated as an
alternative energy source, afforded the compound 3a
in 65% yield after 1 h (Table 1, entry 22). Finally, one
experiment was conducted under a N2 atmosphere,
9
K2CO3 (10)
Cs2CO3
(10)
DMSO
DMSO
70
70
traces
6
58
49
10
KOtBu
(10)
11
DMSO
70
16
53
12
13
14
KOH (10)
DBU (20)
DBU (20)
DMSO
DMSO
DMSO
70
70
100
34
53
50
22
9
77
92
15
DBU (20)
DMSO
120
traces giving product 3a in 85% yield (Table 1, entry 23).
(86)c
62
16
17
18
19
20
21
22d
DBU (10)
KOH (20)
DBU (20)
DBU (20)
DBU (20)
DBU (20)
DBU (20)
DBU (20)
DMSO
DMSO
toluene
DMF
MeCN
120
120
111
120
82
120
120
120
27
16
15
19
49
traces
23
traces
Scope of the Reaction
63
-
47
17
-
With the best conditions in hand, we tested the
generality and limitations of our methodology,
reacting 2-azidobenzaldehyde 1a with different
ethyleneglycol
DMSO
substituted β-keto esters 2a-f and 1,3-diketones 2g-l
65
85
(Scheme 3). When the ethyl group of the β-keto ester
23e
DMSO
2a was changed for tert-butyl (2b) or isopentyl group
a
Reactions were carried out using 2-azidobenzaldehyde 1a (0.25 mmol)
and ethyl acetoacetate 2a (0.25 mmol) in 0.25 mL of solvent under air
atmosphere for 24 h. The reaction progress was followed by TLC. b Yields
(2c), a significant decrease in the yield was observed,
and the respective [1,2,3]triazolo[1,5-a]quinolines 3b
and 3c were obtained in 66% and 75% yield. Other
alkoxyl groups were also evaluated, such as 2-
phenethyl (2d), benzyl (2e), and prop-2-yn-1-yl (2f),
giving the desired products 3d-f in 48%, 51%, and
30% yield, respectively.
c
are given for isolated products. Yield in parentheses correspond to
reactions performed on a 2.5 mmol scale. Reaction performed under
microwave irradiation at 120 °C for 1 h. Reaction performed under N2
d
e
atmosphere.
The complete structural characterization of the
compound 3a was achieved by 1D and 2D-NMR
techniques, such as COSY, HSQC, and HMBC. After
analyzing the NMR spectra, it was possible to
discriminate and attribute all the hydrogen and carbon
The reaction of 2-azidobenzaldehyde 1a with
pentane-2,4-dione 2g and with 1-phenylbutane-1,3-
dione
2h
furnished
the
corresponding
[1,2,3]triazolo[1,5-a]quinolines 3g and 3h, substituted
with ketone groups, in 71% and 68% yield,
3
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
respectively. When the reaction of 1a was carried out fused triazole 5a in 75% yield, together with the
with a range of 1-arylbutane-1,3-diones 2i-l bearing triazole intermediate 6a (ethyl 1-(2-acetylphenyl)-5-
both electron-donating groups (EDG) or electron- methyl-1H-1,2,3-triazole-4-carboxylate), which was
withdrawing
groups
(EWG),
the
desired isolated in 16% yield. In addition, we investigate the
[1,2,3]triazolo[1,5-a]quinolines 3i-l were obtained in substrate scope with respect to other β-keto esters 2b-
moderate to good yields. Interesting, the electron-rich f and 1,3-diketones 2g-l. The desired products 5 were
1-(4-methoxy-phenyl)butane-1,3-dione 2i was
a
obtained generally in lower yields compared to the
suitable substrate for the reaction, affording the reactions using 2-azidobenzaldehyde 1a as a starting
desired product 3i in a very good 85% yield, while 1- material (Scheme 3). These results could be attributed,
arylbutane-1,3-diones 2h and 2j-l afforded the at least in part, to the steric hindrance due to the
respective products in moderate yields (Scheme 3). methyl group in 2-azidoacetophenone 1b, when
These results suggest that the electron-donating compared to the aldehyde 1a. Interesting, the reaction
methoxy group could facilitate the intramolecular involving 1b and the aryl 1,3-diketones 2h-l was less
condensation step (see Scheme 6, the mechanism sensitive to electronic effects in the pendant aromatic
proposal). When 1-(2-methoxy-phenylbutane)-1,3- ring if compared with the reaction using aldehyde 1a,
dione 2l was used as the substrate, the desired product even if the fused triazole p-methoxy-substituted 5i
3l was obtained in 71% yield, despite the steric was obtained in a slightly higher yield (70%).
hindrance caused by the ortho-substitution.
Following, we examined the suitableness of our
protocol in the reaction of 2-azidobenzophenones 1c-e
with ethyl acetoacetate 2a. The expected fused
triazoles 7a-c were obtained in good to very good
yields under the optimal reaction conditions. For
instance,
product
7a,
derived
from
2-
azidobenzophenone 1c, was obtained in 89% yield,
while the para-substituted benzophenones 1d and 1e
reacted with 2a to afford the respective products 7b
and 7c in 84% and 70% yield, respectively (Scheme
3). While the presence of the electron-withdrawing
fluoro group did not influence the reactivity of
substrate 1d, the electron-donating one methoxy
caused a decrease in the reactivity of 1c, probably due
to the decrease in the electrophilicity of the carbonyl
group (Scheme 3, compound 7b vs. 7c).
Scheme
4 - Reactivity of different 1,3-dicarbonyl
compounds.
Scheme
3.
Generality
in
the
synthesis
of
The reactivity of different 1,3-dicarbonyl compounds
with 2-azidobenzaldehyde 1a was then examined.
Thus, the reaction of 3,5-heptanedione 2m with 1a,
under our conditions, gave the 1,2,3-triazole 4m
exclusively as the product of the intermolecular [3+2]
cycloaddition reaction, in 82% yield (Scheme 4, eq.
1). A similar result was obtained when N-(4-
chlorophenyl)-3-oxobutanamide 2n was used as the
substrate in the reaction with 1a, and product 4n was
isolated in 84% yield, with the expected fused triazole
3n being observed in trace amounts (Scheme 4, eq. 2).
To verify if the free N-H in the amide 2n was
[1,2,3]triazolo[1,5-a]quinolines. Reactions were carried out
using azides 1a-b (0.25 mmol), the carbonyl compound 2a-
l (0.25 mmol), DBU (20 mol%), in DMSO (0.25 mL) at
120 °C under air atmosphere. The reaction progress was
followed by TLC, and the yields are given for isolated
products.
The strategy above was successfully extended to the
reaction of 2’-azidoacetophenone 1b with different
substituted β-keto esters and 1,3-diketones. For
instance, the reaction of 1b with ethyl acetoacetate 2a
under the optimal conditions afforded the respective
4
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
preventing the cyclization step, N,N-diethyl-3- benzaldehyde 8a or 2-nitrobenzaldehyde 8b, under
oxobutanamide 2o was used as starting material. the standard conditions (Scheme 5, Eq. 3). The
However, the desired [1,2,3]triazolo[1,5-a]quinoline condensation products 10a, 10b or 10c were not
3o was not observed, and the 1,2,3-triazole 4o was the obtained and the starting materials were recovered.
only product, isolated in 65% yield (Scheme 4, eq. 3). These results indicates that the formation of the
These results prove that the intramolecular thermodynamically
stable
[1,2,3]triazolo[1,5-
condensation reaction cannot be extended to amides.
a]quinoline 3 aromatic system is essential for the
accomplishment of the second cyclization step.
Mechanism Discussion
Considering the results obtained in the control
experiments and the data in the literature on the
synthesis of 1,2,3-triazoles using DBU as a catalyst,[6]
a plausible mechanism for this one‐pot sequential
organocatalytic synthesis of [1,2,3]triazolo[1,5-
a]quinoline 3 is presented in Scheme 6. Firstly, the
enolate 2’ is formed by the abstraction of one
methylene acidic proton from compound 2 by DBU.
Then, a [3+2] cycloaddition reaction occurs between
enolate 2’ and 2-azidobenzaldehyde 1a, generating
the intermediate triazoline A, which subsequently
dehydrates, forming the 1,2,3-triazole intermediate 4.
Following, the 1,2,3-triazole intermediate 4 reacts
with DBU, which abstracts a proton from the methyl
group at the 5-position of triazole 4, with the electron
displacement by the triazole nucleus and the carbonyl,
forming the enolate intermediate B. Then, the
negative charge present in the oxygen migrates, so
that the carbon bonded at position 5 of the triazole
performs a nucleophilic attack to the pendent ortho-
carbonyl group, forming the intermediate C, which
after a dehydration step forms the [1,2,3]triazolo[1,5-
a]quinoline 3. We assume that the driving force for
this intramolecular condensation reaction is the
aromatization in the formation of the fused
[1,2,3]triazolo[1,5-a]quinoline heterocycle 3.
In order to collect data to subsidize a plausible
mechanism for the reaction, some control experiments
were conducted. Initially, the reaction between
2-azidobenzaldehyde 1a and ethyl acetoacetate 2a
under the standard conditions was performed in the
presence of TEMPO (3 equiv.). The products 3a and
4a were obtained in 74% and 14% yield, respectively.
This outcome indicates that the reaction does not
occur via a radical pathway (Scheme 5, Eq. 1). In
order to confirm the hypothesis that the 1,2,3-triazole
4a is the intermediate of the reaction, 4a was used as
starting material under the standard conditions, giving
the product 3a in 95% yield after 24 h (Scheme 5, Eq.
2A). Further, we observed that the cyclization did not
occur in the absence of DBU, with 4a remaining
unreacted, proving the importance of DBU in the
intramolecular condensation step (Scheme 5, Eq. 2B).
Using the NOESY (Nuclear Overhauser Enhancement
Spectroscopy) technique, it is possible to calculate the
distance between the nearby hydrogens in
a
molecule,[19] and thus establish the molecular
geometry of the compound through studies described
by Bell and Saunders in 1970.[20] After the analysis
and calculations of compound 4a, the results suggest
that the proximity between H-8 methyl hydrogens and
aldehydic H-1 is essential to the intramolecular
condensation step (Figure 2). Since DBU is a bulky
base and the 1,2,3-triazole nucleus is almost
perpendicular to the aromatic ring, the methyl group
is turned out of the geometric plane, facilitating the
proton abstraction from the methyl group and thus
carrying out the intramolecular condensation reaction.
Scheme 5 - Control experiments.
Finally, in order to verify the acidity of the methyl
proton bonded at the 5-position of triazole 4, we
performed one reaction between 1,2,3-triazole 9 and
the corresponding aldehydes 2-azidobenzaldehyde 1a,
5
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
Scheme 6. Proposed mechanism.
in 10% of H2SO4 under heating conditions as developing
agents. Merck silica gel (particle size 0.040-0.063 mm)
was used to flash chromatography. Hydrogen nuclear
magnetic resonance spectra (1H NMR) were obtained on
Bruker Avance III HD 400 spectrometer at 400 MHz. The
spectra were recorded in CDCl3 solutions. The chemical
shifts are reported in ppm, referenced to tetramethylsilane
(TMS) as the internal reference. Coupling constants (J) are
reported in Hertz. Abbreviations to denote the multiplicity
of a particular signal are s (singlet), d (doublet), dd
(doublet of doublet) t (triplet), q (quartet), quint (quintet),
and m (multiplet). Carbon-13 nuclear magnetic resonance
spectra (13C NMR) were obtained on Bruker Avance III
HD 400 spectrometer at 100 MHz. The chemical shifts are
reported in ppm, referenced to the solvent peak of CDCl3.
The high-resolution electrospray ionization mass
spectrometry (ESI-QTOF) analysis were performed on a
Bruker Daltonics micrOTOF-Q II instrument in positive
mode. The samples were solubilized in HPLC-grade
acetonitrile and injected into the ESI source by means of a
syringe pump at a flow rate of 5.0 µL min-1. The following
instrument parameters were applied: capillary and cone
voltages were set to +3500 V and -500 V, respectively,
with a desolvation temperature of 180 °C. For data
acquisition and processing, Compass 1.3 for micrOTOF-Q
II software (Bruker daltonics, USA) was used. Low-
resolution mass spectra were obtained with a Shimadzu
GC-MS-QP2010 mass spectrometer. Melting point (mp)
values were measured in a Marte PFD III instrument with a
0.1 °C precision.
Figure 2. Distance between nearby hydrogens in the
compound 4a.
Conclusion
In summary, we have developed an one‐pot
sequential organocatalytic method for the synthesis of
fused [1,2,3]triazolo[1,5-a]quinolines in yields
ranging from moderate to excellent. A total of
twenty-seven [1,2,3]triazolo[1,5-a]quinolines were
synthesized by the successive intermolecular [3+2]-
cycloaddition between 1,3-dicarbonyl compounds
and o-carbonyl substituted phenyl azides, followed by
an intramolecular condensation reaction of the 1,2,3-
triazole intermediates. All the reactions were
performed using DBU as a catalyst, and DMSO as
solvent at 120 °C for 24 h. This protocol tolerates a
range of 1,3-dicarbonyl compounds, such as β-keto
esters and 1,3-diketones, and o-formyl, o-acetyl, or o-
benzoyl-substituted phenylazides.
General
procedure
for
the
synthesis
of
[1,2,3]triazolo[1,5-a]quinolines 3a-l, 5a-I, and 7a-c:
Azide 1a-e (0.25 mmol), 1,3-dicarbonyl compound 2a-l
(0.25 mmol), DBU (20 mol%, 0.0076 g) and DMSO (0.25
mL) were added to a 5.0 mL glass tube. Then, the reaction
mixture was stirred for 24 h at 120 °C under air
atmosphere. After this time, the crude product was purified
by column chromatography on silica gel with a mixture of
hexane/ethyl acetate (5:1) as eluent to afford the desired
product (3a-l, 5a-l and 7a-c). Spectral data for the products
prepared are listed below.
Experimental Section
Materials and methods
The reactions were monitored by TLC carried out on
Merck silica gel (60 F254) by using UV light as
visualization agent and the mixture between 5% of vanillin
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000887
Advanced Synthesis & Catalysis
Ethyl [1,2,3]triazolo[1,5-a]quinoline-3-carboxylate (3a):
Yield: 0.055 g (92%), white solid, mp: 137 - 139 °C; H
128.8, 128.6, 128.5, 127.9, 124.1, 116.7, 115.6, 66.9. MS
(rel. int., %) m/z: 303.2 (5.8), 274.1 (1.2), 197.1 (7.7),
156.1 (21.0), 128.2 (96.8), 91.2 (100.0).HRMS (ESI-
QTOF) calculated mass for C18H14N3O2 [M+H]+: 304.1081,
found: 304.1087.
1
NMR (CDCl3, 400 MHz)  (ppm) = 8.82 (d, J = 8.4 Hz,
1H), 8.06 (d, J = 9.3 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H),
7.84-7.80 (m, 1H), 7.77 (d, J = 9.3 Hz, 1H), 7.68-7.64 (m,
1H), 4.55 (q, J = 7.1 Hz, 1H), 1.51 (t, J = 7.1 Hz, 1H).
13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 162.0, 134.0,
131.9, 131.7, 131.2, 130.7, 129.1, 128.2, 124.4, 116.9,
115.9, 61.6, 14.9. MS (rel. int., %) m/z: 241.0 (19.8), 213.0
(1.6), 196.0 (4.1), 169.1 (16.8), 128.2 (100.0), 113.1 (11.6),
101.1 (14,7), 88.1 (3.8). HRMS (ESI-QTOF) calculated
mass for C13H12N3O2 [M+H]+: 242.0924, found: 242.0937.
Prop-2-yn-1-yl
[1,2,3]triazolo[1,5-a]quinoline-3-
carboxylate (3f): Yield: 0.019 g (30%); yellowish solid,
1
mp: 165 - 167 °C; H NMR (CDCl3, 400 MHz)  (ppm) =
8.85 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 11.0 Hz, 1H), 7.94 (d,
J = 8.0 Hz, 1H), 7.87 – 7.82 (m, 2H), 7.72-7.68 (m, 1H),
5.08 (d, J = 2.4 Hz, 2H), 2.58 (t, J = 2.4 Hz, 1H). 13C{1H}
NMR (CDCl3, 100 MHz)  (ppm) = 160.8, 134.0, 131.7,
131.2, 130.9, 130.6, 128.9, 128.0, 124.1, 116.7, 115.5, 77.6,
75.6, 52.6. MS (rel. int., %) m/z: 251.0 (17.1), 222.0 (32.0),
194.0 (22.9), 166.1 (28.6), 140.1 (33.7), 128.1 (100.0),
101.1 (26.7), 88.1 (10.4). HRMS (ESI-QTOF) calculated
mass for C14H10N3O2 [M+H]+: 252.0768, found: 252.0765.
tert-Butyl [1,2,3]triazolo[1,5-a]quinoline-3-carboxylate
(3b): Yield: 0.044 g (66%); yellow solid, mp: 134 -
1
136 °C; H NMR (CDCl3, 400 MHz)  (ppm) = 8.83 (d, J
= 8.4 Hz, 1H), 8.03 (d, J = 9.3 Hz, 1H), 7.90 (dd, J = 8.0,
1.0 Hz, 1H), 7.83-7.79 (m, 1H), 7.75 (d, J = 9.3 Hz, 1H),
7.68-7.64 (m, 1H), 1.72 (s, 9H). 13C{1H} NMR (CDCl3,
100 MHz)  (ppm) = 160.9, 133.3, 132.7, 131.7, 130.8,
130.0, 128.7, 127.8, 124.0, 116.6, 115.9, 82.4, 28.5. MS
(rel. int., %) m/z: 269.1 (6.4), 213.1 (13.1); 196.0 (6.5),
185.1 (8.9), 169.1 (7.9), 156.1 (6.4), 140.1 (33.3), 129.1
(100.0), 113.1 (18.5), 102.1 (15.6). HRMS (ESI-QTOF)
calculated mass for C15H16N3O2 [M+H]+: 270.1237, found:
270.1241.
1-([1,2,3]Triazolo[1,5-a]quinolin-3-yl)ethan-1-one (3g):
1
Yield: 0.037 g (71%); white solid, mp 160 - 162 °C; H
NMR (CDCl3, 400 MHz)  (ppm) = 8.85 (d, J = 8.4 Hz,
1H), 8.23 (d, J = 9.2 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H),
7.88 – 7.82 (m, 2H), 7.71 – 7.67 (m, 1H), 2.86 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 193.9, 139.0,
132.3, 131.5, 131.2, 131.1, 128.8, 127.9, 124.4, 116.7,
116.3, 27.6. MS (rel. int., %) m/z: 211.1 (12.8), 183.1
(25.7), 154.1 (100.0), 140.1 (14.2), 128.1 (22.1), 113.1
(10.7), 88.1 (5.1). HRMS (ESI-QTOF) calculated mass for
C12H9N3ONa [M+H]+: 234.0638, found: 234.0631.
Isopentyl [1,2,3]triazolo[1,5-a]quinoline-3-carboxylate
(3c): Yield: 0.053 g (75%); yellow solid, mp: 139 -
1
141 °C; H NMR (CDCl3, 400 MHz)  (ppm) = 8.86 (d, J
= 8.3 Hz, 1H), 8.09 (d, J = 9.2 Hz, 1H), 7.93 (d, J = 7.8 Hz,
1H), 7.86 – 7.79 (m, 2H), 7.70-7.67 (m, 1H), 4.52 (t, J =
6.7 Hz, 2H), 1.90 - 176 (m, 3H), 1.01 (d, J = 6.2 Hz, 6H).
13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 161.8, 133.7,
131.8, 131.5, 131.0, 130.4, 128.8, 127.9, 124.1, 116.7,
115.7, 64.0, 37.6, 25.3, 22.7. MS (rel. int., %) m/z: 212.0
(4.9), 169.1 (27.9), 157.1 (10.5), 140.2 (32.3), 128.1
(100.0), 102.1 (12.2), 88.1 (31.6). HRMS (ESI-QTOF)
calculated mass for C16H18N3O2 [M+H]+: 284.1394, found:
284.1395.
[1,2,3]Triazolo[1,5-a]quinolin-3-yl(phenyl)methanone
(3h): Yield.: 0.047 g (68%); yellowish solid, mp: 150 -
152 °C; H NMR (CDCl3, 400 MHz)  (ppm) = 8.82 (d, J
1
= 8.4 Hz, 1H), 8.54 (d, J = 7.5 Hz, 2H), 8.34 (d, J = 9.2 Hz,
1H), 7.89 (d, J = 8.0 Hz, 1H), 7.83 – 7.79 (m, 2H), 7.66-
7.61 (q, m, 2H), 7.57-7.53 (q, m, 2H). 13C{1H} NMR
(CDCl3, 100 MHz)  (ppm) = 186.6, 138.7, 137.4, 134.6,
132.9, 131.4, 131.1, 131.0, 130.7, 128.7, 128.4, 127.9,
124.5, 116.7, 116.6. MS (rel. int., %) m/z: 273.0 (6.7),
245.0 (45.5), 217.0 (100.0), 163.1 (2.6), 140.1 (5.7), 113.1
(8.3), 88.0 (5.1). HRMS (ESI-QTOF) calculated mass for
C17H12N3O [M+H]+: 274.0975, found: 274.0971.
1-Phenylethyl
[1,2,3]triazolo[1,5-a]quinoline-3-
carboxylate (3d): Yield: 0.038 g (48%); gray solid, mp:
129 - 131 °C; 1H NMR (CDCl3, 400 MHz)  (ppm) = 8.76
(d, J = 8.4 Hz, 1H), 7.97 (d, J = 9.3 Hz, 1H), 7.82 (d, J =
7.9 Hz, 1H), 7.76-7.72 (m, 1H), 7.68 (d, J = 9.3 Hz, 1H),
7.60-7.52 (m, 1H), 7.46 (d, J = 7.4 Hz, 2H), 7.32-7.29 (m,
2H), 7.25-7.21 (m, 1H), 6.21 (q, J = 6.6 Hz, 1H), 1.71 (d, J
= 6.6 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz)  (ppm)
= 161.0, 141.6, 133.8, 131.7, 131.5, 131.0, 130.4, 128.8,
128.7, 128.2, 127.9, 126.4, 124.1, 116.7, 115.7, 73.5, 22.6.
MS (rel. int., %) m/z: 317.1 (2.8), 244.1 (4.8), 213.0 (3.5),
197.0 (6.7), 156.1 (9.4), 128.1 (31.9), 105.1 (100.0).
HRMS (ESI-QTOF) calculated mass for C19H16N3O2
[M+H]+: 318.1237, found: 318.1237.
[1,2,3]Triazolo[1,5-a]quinolin-3-yl(4-
methoxyphenyl)methanone (3i): Yield: 0.064 g (85%);
1
white solid, mp: 170 - 172 °C, H NMR (CDCl3, 400
MHz)  (ppm) = 8.83 (d, J = 8.4 Hz, 1H), 8.63 (d, J = 8.9
Hz, 2H), 8.34 (d, J = 9.3 Hz, 1H), 7.89 (d, J = 7.9 Hz, 1H),
7.83-7.79 (m, 2H), 7.66-7.62 (m, 1H), 7.03 (d, J = 8.9 Hz,
2H), 3.91 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) 
(ppm) = 185.0, 163.6, 139.0, 134.6, 133.2, 131.4, 130.9,
130.8, 130.3, 128.7, 127.8, 124.5, 116.9, 116.5, 113.7, 55.6.
MS (rel. int., %) m/z: 303.0 (4.4), 275.0 (71.1), 247.0
(19.2), 232.0 (79.8), 216.0 (7.2), 204.0 (100.0), 176.0
(11.9), 128.0 (10.1), 101.0 (11.6), 88.0 (9.4). HRMS (ESI-
QTOF) calculated mass for C20H18N3O3 [M+H]+: 304.1086,
found: 304.1091.
Benzyl
[1,2,3]triazolo[1,5-a]quinoline-3-carboxylate
(3e): Yield: 0.038 g (51%); yellowish solid, mp: 132 -
1
134 °C; H NMR (CDCl3, 400 MHz)  (ppm) = 8.75 (d, J
[1,2,3]Triazolo[1,5-a]quinolin-3-yl(4-
= 8.4 Hz, 1H), 7.95 (d, J = 9.3 Hz, 1H), 7.82 (d, J = 7.9 Hz,
1H), 7.76-7.72 (m, 1H), 7.68 (d, J = 9.3 Hz, 1H), 7.60-7.56
(m, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.34 – 7.25 (m, 3H),
5.44 (s, 2H). 13C{1H} NMR (CDCl3, 100 MHz)  (ppm) =
161.5, 135.9, 133.8, 131.7, 131.2, 131.0, 130.6, 128.8,
methylphenyl)methanone (3j): Yield: 0.050 g (69%);
1
yellowish solid, mp: 168 - 170 °C; H NMR (CDCl3, 400
MHz)  (ppm) = 8.84 (d, J = 8.4 Hz, 1H), 8.47 (d, J = 8.2
Hz, 2H), 8.35 (d, J = 9.3 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H),
7.84-7.81 (m, 2H), 7.67-7.63 (m, 1H), 7.35 (d, J = 8.0 Hz,
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000887
Advanced Synthesis & Catalysis
2H), 2.46 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) 
(ppm) = 186.3, 143.9, 139.0, 134.9, 134.6, 131.5, 130.9,
130.9, 129.2, 128.7, 127.9, 124.5, 116.8, 116.6, 21.9. MS
(rel. int., %) m/z: 287.0 (4.1), 259.0 (45.7), 230.0 (100.0),
216.0 (19.9), 202.0 (9.6), 189.0 (4.5), 140.0 (5.2), 114.1
(11.1). HRMS (ESI-QTOF) calculated mass for C18H14N3O
[M+H]+: 288.1131, found: 288.1135.
Isopentyl
5-methyl-[1,2,3]triazolo[1,5-a]quinoline-3-
carboxylate (5c): Yield: 0.052 g (70%); pink solid, mp:
144 - 146 °C; 1H NMR (CDCl3, 400 MHz)  (ppm) = 8.89
(d, J = 8.3 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.94 (s, 1H),
7.86-7.82 (m, 1H), 7.73-7.69 (m, 1H), 4.51 (t, J = 6.9 Hz,
2H), 2.73 (s, 3H), 1.91-1.76 (m, 3H), 1.01 (d, J = 6.4 Hz,
6H). 13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 162.0,
138.4, 133.6, 131.5, 130.7, 130. 7, 127.8, 125.6, 124.5,
117.0, 114.7, 63.9, 37.6, 25.3, 22.7, 19.8. MS (rel. int., %)
m/z: 297.1 (14.9), 183.0 (41.9), 170.1 (30.6), 154.1 (23.6),
142.1 (100.0), 127.1 (22.1),115.1 (25.0). HRMS (ESI-
QTOF) calculated mass for C17H20N3O2 [M+H]+: 298.1550,
found: 298.1545.
[1,2,3]Triazolo[1,5-a]quinolin-3-yl(4-
fluorophenyl)methanone (3k): Yield: 0.045 g (62%);
1
white solid, mp: 205 - 207 °C; H NMR (CDCl3, 400
MHz)  (ppm) = 8.88 (d, J = 8.4 Hz, 1H), 8.67 – 8.63 (m,
2H), 8.38 (d, J = 9.3 Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H),
7.90 – 7.85 (m, 2H), 7.73 – 7.69 (m, 1H), 7.27 – 7.21 (m,
2H). 13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 185.0,
1-Phenylethyl 5-methyl-[1,2,3]triazolo[1,5-a]quinoline-
165.9 (d, J = 254.6 Hz), 138.7, 134.8, 133.8 (d, J = 3.0 Hz), 3-carboxylate (5d): Yield: 0.042 g (51%); pink solid, mp:
133.5 (d, J = 9.2 Hz), 131.5, 131.3, 131.2, 128.8, 128.0,
124.6, 116.8, 116.7, 115.6 (d, J = 21.7 Hz). MS (rel.
int., %) m/z: 291.0 (5.1), 263.0 (51.1), 235.0 (100.0), 214.0
163 - 165 °C; 1H NMR (CDCl3, 400 MHz)  (ppm) = 8.88
(d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.92 (s, 1H),
7.85-7.81 (m, 1H), 7.72-7.68 (m, 1H), 7.55 (d, J = 7.3 Hz,
(12.8), 207.0 (21.3), 175.0 (5.2), 149.1 (17.8), 138.1 (10.1), 2H), 7.40-7.37 (m, 2H), 7.33-7.29 (m, 1H), 6.27 (q, J = 6.6
123.0 (38.6), 111.1 (22.1), 98.1 (16.8), 88.0 (23.6). HRMS
(ESI-QTOF) calculated mass for C17H11FN3O [M+H]+:
292.0881, found: 292.0872.
Hz, 1H), 2.70 (s, 3H), 1.79 (d, J = 6.6 Hz, 3H). 13C{1H}
NMR (CDCl3, 100 MHz)  (ppm) = 161.3, 141.8, 138.4,
133.7, 131.5, 130.7, 130.6, 128.7, 128.1, 127.7, 126.4,
125.6, 124.5, 117.0, 114.8, 73.4, 22.7, 19.8. MS (rel.
int., %) m/z: 331.1 (1.4), 183.1 (3.0), 154.1 (6.1), 142.1
(37.2), 16.1 (11.3), 105.1 (100.0), 88.0 (7.4). HRMS (ESI-
QTOF) calculated mass for C20H18N3O2 [M+H]+: 332.1394,
found: 332.1389.
[1,2,3]Triazolo[1,5-a]quinolin-3-yl(2-
methoxyphenyl)methanone (3l): Yield: 0.054 g (71%);
yellow solid, mp: 131 - 133 °C; 1H NMR (CDCl3, 400
MHz)  (ppm) = 8.80 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 9.2
Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.83 – 7.78 (m, 2H),
7.70 (dd, J = 7.5, 1.5 Hz, 1H), 7.66 – 7.62 (m, 1H), 7.53 –
7.49 (m, 1H), 7.11 – 7.05 (m, 2H), 3.82 (s, 3H). 13C{1H}
NMR (CDCl3, 100 MHz)  (ppm) = 189.1, 158.0, 139.2,
133.4, 132.6, 131.4, 131.0, 130.9, 130.4, 128.7, 127.7,
124.4, 120.4, 116.5, 116.4, 111.9, 55.9. MS (rel. int., %)
m/z: 303.0 (7.2), 260.0 (82.3), 244.4 (100.0), 230.0 (20.5),
218.0 (29.8), 204.0 (20.6), 176.0 (10.0), 129.0 (77.8),
119.0 (11.9), 108.5 (13.8), 101.0 (23.3), 91.0 (43.7).
HRMS (ESI-QTOF) calculated mass for C18H14N3O2
[M+H]+: 304.1081, found: 304.1081.
Benzyl
5-methyl-[1,2,3]triazolo[1,5-a]quinoline-3-
carboxylate (5e): Yield: 0.041 g (52%); pink solid, mp:
141 - 143 °C; 1H NMR (CDCl3, 400 MHz)  (ppm) = 8.87
(d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.91 (s, 1H),
7.85-7.81 (m, 1H), 7.72-7.68 (m, 1H), 7.55 (d, J = 7.1 Hz,
2H), 7.42 – 7.35 (m, 3H), 5.52 (s, 2H), 2.70 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 161.7, 138.6,
136.0, 133.7, 131.4, 130.7, 130.3, 128.8, 128.6, 128.5,
127.8, 125.6, 124.5, 117.0, 114.7, 66.8, 19.7. MS (rel.
int., %) m/z: 317.0 (8.5), 288.1 (1.8), 170.0 (16.6), 142.1
(100.0), 115.1 (18.2), 91.1 (86.4). HRMS (ESI-QTOF)
calculated mass for C19H16N3O2 [M+H]+: 318.1237, found:
318.1243.
Ethyl
5-methyl-[1,2,3]triazolo[1,5-a]quinoline-3-
carboxylate (5a): Yield: 0.047 g (75%); yellow solid, mp:
131 - 133 °C; 1H NMR (CDCl3, 400 MHz)  (ppm) = 8.87
(d, J = 8.3 Hz, 1H), 8.00 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H),
7.84-7.81 (m, 1H), 7.72-7.68 (m, 1H), 4.55 (q, J = 7.1 Hz,
2H), 2.72 (s, 3H), 1.51 (t, J = 7.1 Hz, 3H). 13C{1H} NMR
(CDCl3, 100 MHz)  (ppm) = 161.9, 138.4, 133.6, 131.4,
130.6, 130.6, 127.7, 125.6, 124.5, 117.0, 114.7, 61.3, 19.7,
14.6. MS (rel. int., %) m/z: 255.0 (20.0), 227.0 (2.0), 183.0
(23.0), 170.0 (23.6), 142.1 (100.0), 115.1 (31.0). HRMS
(ESI-QTOF) calculated mass for C14H14N3O2 [M+H]+:
256.1081, found: 256.1082.
1-(5-Methyl-[1,2,3]triazolo[1,5-a]quinolin-3-yl)ethan-1-
one (5g): Yield: 0.039 g (69%); Orange solid, mp: 147 -
1
149 °C; H NMR (CDCl3, 400 MHz)  (ppm) = 8.73 (d, J
= 8.4 Hz, 1H), 7.94 (d, J = 1.0 Hz, 1H), 7.91 (d, J = 8.2 Hz,
1H), 7.79-7.75 (m, 1H), 7.66-7.62 (m, 1H), 2.82 (s, 3H),
2.65 (d, J = 1.0 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz)
 (ppm) = 193.6, 139.2, 138.2, 131.8, 130.9, 130.5, 127.5,
125.3, 124.4, 116.6, 115.0, 27.4, 19.4. MS (rel. int., %)
m/z: 225.0 (15.9), 197.1 (31.6), 168.1 (100.0), 154.1 (12.8),
143.1 (17.2), 115.1 (12.7), 102.1 (3.9). HRMS (ESI-
QTOF) calculated mass for C13H12N3O [M+H]+: 226.0975,
found: 226.0979.
tert-Butyl
5-methyl-[1,2,3]triazolo[1,5-a]quinoline-3-
carboxylate (5b): Yield: 0.045 g (64%), pink solid, mp:
140 - 142 °C; 1H NMR (CDCl3, 400 MHz)  (ppm) = 8.88
(d, J = 8.3 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.91 (s, 1H),
7.84-7.81 (m, 1H), 7.72-7.68 (m, 1H), 2.71 (s, 3H), 1.71 (s,
9H). 13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 161.3,
138.0, 133.3, 131.8, 131.5, 130.6, 127.6, 125.6, 124.5,
117.0, 115.0, 82.4, 28.6, 19.7. MS (rel. int., %) m/z: 283.1
(9.1), 227.0 (4.9), 210.0 (8.1), 154.1 (23.4), 143.1 (100.0),
115.1 (14.1), 85.1 (4.9). HRMS (ESI-QTOF) calculated
mass for C16H18N3O2 [M+H]+: 284.1394, found: 284.1384.
(5-Methyl-[1,2,3]triazolo[1,5-a]quinolin-3-
yl)(phenyl)methanone (5h): Yield: 0.045 g (63%); yellow
1
solid, mp: 156 - 158 °C; H NMR (CDCl3, 400 MHz) 
(ppm) = 8.79 (d, J = 8.3 Hz, 1H), 8.53 (d, J = 7.3 Hz, 2H),
8.14 (s, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.79-7.75 (m, 1H),
7.64 – 7.59 (m, 2H), 7.56 – 7.52 (m, 2H), 2.67 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 186.5, 139.3,
138.0, 137.5, 134.3, 132.8, 130.9, 130.7, 130.6, 128.3,
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000887
Advanced Synthesis & Catalysis
127.6, 125.4, 124.6, 116.7, 115.7, 19.6. MS (rel. int., %)
m/z: 287.1 (5.1), 259.1 (35.2), 230.0 (100.0), 216.0 (28.5),
189.0 (5.2), 165.1 (4.1),140.2 (9.3), 116.1 (20.5), 102.1
(8.4), 88.1 (14.1). HRMS (ESI-QTOF) calculated mass for
C18H14N3O [M+H]+: 288.1131, found: 288.1134.
QTOF) calculated mass for C19H16N3O2 [M+H]+: 318.1237,
found: 318.1238.
Ethyl 1-(2-acetylphenyl)-5-methyl-1H-1,2,3-triazole-4-
1
carboxylate (6a): Yield: 0.011 g (16%); reddish oil; H
NMR (CDCl3, 400 MHz)  (ppm) = 7.90 – 7.88 (m, 1H),
7.73 – 7.68 (m, 2H), 7.38-7.36 (m, 1H), 4.46 (q, J = 7.1 Hz,
2H), 2.47 (s, 3H), 2.32 (s, 3H), 1.45 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 198.0, 161.8,
140.9, 136.8, 136.4, 132.9, 132.6, 131.1, 129.7, 128.5, 61.2,
29.0, 14.4, 9.7. MS (rel. int., %) m/z: 273.1 (26.0), 228.0
(20.9), 172.1 (58.8), 157.1 (100.0), 144.1 (68.9), 130.1
(57.5), 91.1 (94.3). HRMS (ESI-QTOF) calculated mass
for C14H16N3O3 [M+H]+: 274.1186, found: 274.1194.
(4-Methoxyphenyl)(5-methyl-[1,2,3]triazolo[1,5-
a]quinolin-3-yl)methanone (5i): Yield: 0.056 g (70%);
1
white solid, mp: 153 - 155 °C; H NMR (CDCl3, 400
MHz)  (ppm) = 8.80 (d, J = 8.3 Hz, 1H), 8.62 (d, J = 8.9
Hz, 2H), 8.15 (s, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.79-7.75
(m, 1H), 7.65-7.61 (m, 1H), 7.02 (d, J = 8.9 Hz, 2H), 3.90
(s, 3H), 2.68 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) 
(ppm) = 184.9, 163.5, 138.9, 138.3, 134.3, 133.1, 131.0,
130.5, 130.4, 127.6, 125.4, 124.7, 116.7, 115.9, 113.6, 55.5,
19.6. MS (rel. int., %) m/z: 317.0 (5.0), 289.0 (79.9), 261.0
(21.3), 246.0 (100.0), 218.0 (65.1), 203.0 (18.2), 189.0
(4.8), 140.0 (4.4), 115.0 (13.4). HRMS (ESI-QTOF)
calculated mass for C19H16N3O2 [M+H]+: 318.1237, found:
318.1235.
Ethyl
5-phenyl-[1,2,3]triazolo[1,5-a]quinoline-3-
carboxylate (7a): Yield: 0.071 g (89%); white solid, mp:
178 - 180 °C; 1H NMR (CDCl3, 400 MHz)  (ppm) = 8.95
(d, J = 8.4 Hz, 1H), 8.05 (s, 1H), 7.90 – 7.83 (m, 2H), 7.64
– 7.60 (m, 1H), 7.57 – 7.50 (m, 5H), 4.54 (q, J = 7.1 Hz,
2H), 1.49 (t, J = 7.1 Hz, 3H).13C{1H} NMR (CDCl3, 100
MHz)  (ppm) =. 161.8, 143.2, 137.4, 133.3, 131.8, 131.6,
130.9, 129.6, 129.0, 128.9, 127.9, 127.7, 123.7, 116.9,
115.3, 61.3, 14.6.MS (rel. int., %) m/z: 317.2 (12.5), 289.2
(2.1), 245.2 (27.6), 232.1 (18.9), 217.1 (26.3), 204.1
(100.0) 176.1 (9.5). HRMS (ESI-QTOF) calculated mass
for C19H16N3O2 [M+H]+: 318.1237, found: 318.1240.
(5-Methyl-[1,2,3]triazolo[1,5-a]quinolin-3-yl)(4-
methylphenyl)methanone (5j): Yield: 0.046 g (61%);
1
yellowish solid, mp: 166 - 168 °C; H NMR (CDCl3, 400
MHz)  (ppm) = 8.82 (d, J = 8.3 Hz, 1H), 8.47 (d, J = 8.1
Hz, 2H), 8.17 (s, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.81 – 7.77
(m, 1H), 7.66 – 7.62 (m, 1H), 7.34 (d, J = 8.0 Hz, 2H),
2.69 (s, 3H), 2.45 (s, 3H). 13C{1H} NMR (CDCl3, 100
MHz)  (ppm) = 186.2, 143.6, 139.1, 138.2, 135.0, 134.3,
131.1, 130.9, 130.6, 129.1, 127.6, 125.4, 124.7, 116.8,
115.8, 21.8, 19.6. MS (rel. int., %) m/z: 301.0 (5.8), 281.0
(6.7), 273.0 (54.6), 244.0 (100.0), 230.0 (50.3), 151.0
(29.0), 135.1 (33.4), 121.1 (39.7), 109.0 (42.3), 96.1 (52.0),
83.1 (95.9). HRMS (ESI-QTOF) calculated mass for
C19H16N3O [M+H]+: 302.1288, found: 302.1286.
Ethyl 5-(4-fluorophenyl)-[1,2,3]triazolo[1,5-a]quinoline-
3-carboxylate (7b): Yield: 0.071 g (84%); white solid,
1
mp:189 - 191 °C; H NMR (CDCl3, 400 MHz)  (ppm) =
8.95 (d, J = 8.3 Hz, 1H), 8.02 (s, 1H), 7.88-7.84 (m, 2H),
7.66-7.62 (m, 1H), 7.53-7.50 (m, 2H), 7.28 – 7.24 (m, 2H),
4.54 (q, J = 7.1 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H).13C{1H}
NMR (CDCl3, 100 MHz)  (ppm) = 163.2 (d, J = 249.1
Hz), 161.8, 142.1, 133.4 (d, J = 3.5 Hz), 133.2, 131.9,
131.4 (d, J = 8.3 Hz), 131.0, 127.8, 127.7, 123.7, 117.0,
116.1 (d, J = 21.7 Hz), 115.5, 61.4, 14.6.MS (rel. int., %)
m/z: 335.2 (10.9), 307.2 (1.6), 278.1 (4.7), 263.1 (24.1),
250.1 (18.1), 235.1 (24.0), 222.1 (100.0), 207.1 (8.0),
175.1 (5.1). HRMS (ESI-QTOF) calculated mass for
(4-Fluorophenyl)(5-methyl-[1,2,3]triazolo[1,5-
a]quinolin-3-yl)methanone (5k): Yield: 0.040 g (53%);
1
white solid, mp: 155 - 158 °C; H NMR (CDCl3, 400
MHz)  (ppm) = 8.83 (d, J = 8.3 Hz, 1H), 8.65 – 8.61 (m,
2H), 8.17 (s, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.84 – 7.80 (m,
1H), 7.70 – 7.66 (m, 1H), 7.23 – 7.19 (m, 2H), 2.71 (s, 3H). C19H15FN3O2 [M+H]+: 336.1143, found: 336.1144.
13C{1H} NMR (CDCl3, 100 MHz)  (ppm) = 184.8, 165.8
Ethyl
5-(4-methoxyphenyl)-[1,2,3]triazolo[1,5-
(d, J = 254.5 Hz), 139.5, 137.9, 134.4, 133.8 (d, J = 2.9
Hz), 133.4 (d, J = 9.2 Hz), 131.1, 130.7, 127.8, 125.5,
124.8, 116.8, 115.7, 115.5 (d, J = 21.6 Hz), 19.7. MS (rel.
int., %) m/z: 305.0 (6.3), 276.9 (41.4), 248.0 (100.0), 233.9
(27.7), 211.8 (10.5), 140.0 (11.9), 116.0 (60.4), 88.0 (33.6).
HRMS (ESI-QTOF) calculated mass for C18H13FN3O
[M+H]+: 306.1037, found: 306.1035.
a]quinoline-3-carboxylate (7c): Yield: 0.060 g (70%);
white solid, mp:184 - 186 °C; 1H NMR (CDCl3, 400 MHz)
 (ppm) = 8.95 (d, J = 9.1 Hz, 1H), 8.02 (s, 1H), 7.94 (d, J
= 8.3 Hz, 1H), 7.87-7.83 (m, 1H), 7.65-7.61 (m, 1H), 7.47
(d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.54 (q, J =
7.1 Hz, 2H), 3.92 (s, 3H), 1.49 (t, J = 7.1 Hz, 3H).13C{1H}
NMR (CDCl3, 100 MHz)  (ppm) =.161.9, 160.3, 143.0,
133.5, 131.9, 131.4, 130.9, 130.8, 129.7, 128.0, 127.6,
124.0, 117.0, 115.1, 114.4, 61.3, 55.6, 14.6MS (rel. int., %)
m/z:. 347.2 (31.9), 319.2 (2.1), 290.2 (29.8), 275.2 (34.5),
262.2 (27.4), 247.1 (67.5), 234.1 (100.0), 2191 (41.1),
204.1 (27.9), 191.1 (20.9). HRMS (ESI-QTOF) calculated
mass for C20H18N3O3 [M+H]+: 348.1343, found: 348.1341.
(2-Methoxyphenyl)(5-methyl-[1,2,3]triazolo[1,5-
a]quinolin-3-yl)methanone (5l): Yield: 0.046 g (58%);
1
orange solid, mp: 170 - 172 °C; H NMR (CDCl3, 400
MHz)  (ppm) = 8.83 (d, J = 8.3 Hz, 1H), 8.16 (s, 1H),
7.98 (d, J = 8.2 Hz, 1H), 7.82 – 7.78 (m, 1H), 7.70 – 7.65
(m, 2H), 7.52 – 7.48 (m, 1H), 7.11 – 7.05 (m, 2H), 3.83 (s,
3H), 2.71 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) 
(ppm) = 189.2, 158.0, 139.3, 138.6, 133.3, 132.4, 131.2,
130.6, 130.4, 128.9, 127.6, 125.5, 124.7, 120.4, 116.8,
115.6, 111.9, 55.9, 19.6. MS (rel. int., %) m/z: 317.0 (8.0),
274.0 (77.6), 258.0 (100.0), 230.0 (30.1), 217.0 (25.5),
143.0 (68.3), 115.0 (46.6), 91.0 (29.5). HRMS (ESI-
General procedure for the synthesis of 1,2,3-triazole 4a:
2-azidobenzaldehyde 1a (0.25 mmol, 0.0368 g), ethyl
acetoacetate 2a (0.25 mmol, 0.0325 g), DBU (10 mol%,
0.0038 g) and DMSO (0.25 mL) were added to a 5.0 mL
glass tube. Then, the reaction mixture was stirred for 24 h
at room temperature under air atmosphere. After this time,
the crude product was purified by column chromatography
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000887
Advanced Synthesis & Catalysis
on silica gel with a mixture of hexane/ethyl acetate (3:1) as
eluent to afford the desired product (4a). Spectral data for
the product 4a prepared are listed below.
12.9, 9.9. MS (rel. int., %) m/z: 286.05 (0.33), 215.05
(93.75), 187.00 (23.55), 158.05 (27.13), 146.10 (100.00),
130.10 (46.72), 118.10 (12.08), 105.05 (16.77), 91.10
(14.58). HRMS (ESI-QTOF) calculated mass for
C15H19N4O2 [M+H]+: 287.1503, found: 287.1509.
Ethyl 1-(2-formylphenyl)-5-methyl-1H-1,2,3-triazole-4-
1
carboxylate (4a): Yield: 0.053 g (82%); yellowish oil; H
NMR (CDCl3, 400 MHz)  (ppm) = 9.67 (s, 1H), 8.13 (dd,
J = 7.5, 1.3 Hz, 1H), 7.87-7.77 (m, 2H), 7.44 (d, J=7.5 Hz,
1H), 4.49 (q, J = 7.1 Hz, 2H), 2.50 (s, 3H), 1.47 (t, J = 7.1
Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz)  (ppm) =
187.9 (2C), 140.9, 135.9, 135.0, 132.0, 131.4, 130.8, 128.2,
61.4, 14.5, 9.8. MS (rel. int., %) m/z: 259.1 (0.6), 231.0
(11.5), 186.0 (12.2), 159.1 (100.0), 143.2 (26.3), 130.1
(99.3), 117.1 (19.3), 103.1 (31.4). HRMS (ESI-QTOF)
calculated mass for C13H14N3O3 [M+H]+: 260.1030, found:
260.1031.
Acknowledgements
The authors are grateful for the financial support and
scholarships from the Brazilian agencies CNPq (Grants
409782/2018-1 and 308015/2019-3) and FAPERGS (PRONEM
16/2551-0000240-1). CNPq is also acknowledged for the
fellowship for E.J.L. and D.A.. This study was partially financed
by the Coordenaꢀꢁo de Aperfeiꢀoamento de Pessoal de Nivel
Superior-Brasil (CAPES)-Finance Code 001.
General procedure for the synthesis of 1,2,3-triazoles
4m-o: 2-azidobenzaldehyde 1a (0.25 mmol, 0.0368 g),
1,3-dicarbonyl compounds 2m-o (0.25 mmol), DBU (20
mol%, 0.0076 g) and DMSO (0.25 mL) were added to a
5.0 mL glass tube. Then, the reaction mixture was stirred
for 24 h at 120 °C under air atmosphere. After this time,
the crude product was purified by column chromatography
on silica gel with a mixture of hexane/ethyl acetate (2:1) as
eluent to afford the desired products (4m-o). Spectral data
for the products prepared are listed below.
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1
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10
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000887
Advanced Synthesis & Catalysis
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
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10.1002/adsc.202000887
Advanced Synthesis & Catalysis
FULL PAPER
Sequential
Organocatalytic
Synthesis
of
[1,2,3]triazolo[1,5-a]quinolines
Adv. Synth. Catal. Year, Volume, Page – Page
Author(s), Corresponding Author(s)*
Gabriel P. da Costa, Mariana F. Bach, Maiara C. de
Moraes, Thiago Barcellos, Eder J. Lenardão,
Márcio S. Silva and Diego Alves*
*
13
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