Click Variations on the Synthesis of 2-Nitrophenyl-4-aryl-1,2,3-triazoles without Isolation of 2-Nitrophenyl Azides

Article abstract of DOI:10.1055/s-0039-1691524

We report a series of efficient procedures to prepare 2-nitrophenyl-4-aryl-1,2,3-triazoles avoiding the isolation of potentially hazardous 2-nitrophenyl azides. An organocatalyzed azide-enolate variant allows efficient access to the target compounds while

Full text of DOI:10.1055/s-0039-1691524

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
cluster
A
en
Synlett
A. Roux, F. Cisnetti
Cluster
Click Variations on the Synthesis of 2-Nitrophenyl-4-aryl-1,2,3-
triazoles without Isolation of 2-Nitrophenyl Azides
Amélie Roux
N
N
N
O
Federico Cisnetti*
0
0
0
0-0
0
0
2-9
4
4
6-
4
6
0
1
not isolated
H
N3
F
Université Clermont Auvergne, CNRS, SIGMA Clermont, ICCF,
3000 Clermont-Ferrand, France
federico.cisnetti@uca.fr
NaN3
NO2
N
X
DBU cat.
6
NO2
NO2
X
X
N
N
Published as part of the ISySyCat2019 Special Issue
EWG
I
Pd cat.
Cu cat.
SiMe3
NO2
X
+
EWG
Received: 14.10.2019
Accepted after revision: 17.11.2019
Published online: 02.12.2019
isolation of potentially hazardous 2-nitrophenyl azides
(
considering that the nitro/azide combination has been
7
DOI: 10.1055/s-0039-1691524; Art ID: st-2019-b0555-c
used as an ‘explosophore’ in energetic materials). In con-
trast to alkyl halides, procedures starting from aryl halides,
8
Abstract We report a series of efficient procedures to prepare 2-nitro-
phenyl-4-aryl-1,2,3-triazoles avoiding the isolation of potentially haz-
ardous 2-nitrophenyl azides. An organocatalyzed azide-enolate variant
allows efficient access to the target compounds while it was shown that
implying a nucleophilic aromatic substitution (S Ar) fol-
N
lowed by AAC, are quite scarce.8 Although some reports
a–e
deal with one-pot, two-step S Ar-CuAAC starting from
N
a
metal-catalyzed azide-alkyne procedure involving
a
preliminary
commercial (substituted) 2-fluoronitrobenzenes, in our
hands these proved unsatisfactory (see below). For this rea-
son, we switched to organocatalyzed azide-enolate cycload-
ditions inspired by the conditions reported by Ramachary
Sonogashira coupling was feasible starting from electron-deficient aryl
iodides.
Key words click chemistry, azides, alkynes, enolates, triazoles,
organocatalysis
9
et al. This synthesis relies on the easy formation of an eno-
late from phenylacetaldehyde. However, the reaction was
reported to require an excess (1.5 equiv) of a preformed, po-
tentially hazardous, aryl azide. In this letter, we describe
variations of this approach that do not require isolation of
the aryl azide, which enhances its synthetic potential. Addi-
tionally, efficient metal-catalyzed tandem reactions to ac-
Click chemistry as a ‘philosophy’ in synthesis1 has
changed the planning of organic chemists’ investigations to-
wards the development of novel compounds. The azide-
alkyne cycloaddition (AAC), especially in its copper-cata-
2
10
lyzed (CuAAC) variant, has proven to be one of the most ef-
cess triazoles have been disclosed. In particular, inspired
fective tools in click chemistry. Among the areas of applica-
by the results reported by Friscourt and Boons on a one-pot,
three-step Sonogashira coupling-desilylation-CuAAC, we
will also present preliminary results on the integration of
3
10a
tion of this reaction, biomolecule modifications and/or
4
medicinal chemistry are prominent.
One of the few limitations of azide-alkyne cycloaddition
is the lack of availability and the hazards of organic azides
such a strategy with an S Ar reaction (Scheme 1).
N
N
N
(
especially if the number of nitrogen atoms is high in com-
F
N
1) NaN3, solvent
N
Ar
N
N
5a
parison to carbon). To mitigate these issues, one-pot pro-
cedures that allow the preparation of 1,4-disubstituted tri-
azoles from alkyl halides, inorganic azide ion and the ap-
propriate reaction partner are very common.5 In these
reports, the high nucleophilicity of the azide ion is exploit-
ed to enable the rapid preparation in the reaction mixture
of an organic azide, which readily undergoes (Cu)AAC.
Recently, we embarked upon a project that required the
preparation of multiple 1-(2-nitrophenyl)-4-aryl-1,2,3-tri-
azoles as precursors to fluorescent compounds (Scheme 1).6
In order to access these triazoles we wanted to avoid the
Ar
2) alkyne
or enolate,
catalyst
NO2
X
N
NO2
X
X
b
Scheme 1 General strategy and structure of the target fluorescent
compounds
First, in order to define efficient conditions for the one-
pot azide-enolate cycloaddition (Scheme 2), we started by
simply applying the conditions defined by Ramachary et
9
al. and we adapted them to a one-pot version with a S Ar
N
©
2019. Thieme. All rights reserved. Synlett 2019, 30, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synlett
A. Roux, F. Cisnetti
Cluster
reaction while concomitantly reducing the excess of 2-ni-
trophenylfluoride from 1.5 to 1.1 equivalent (Table 1, en-
tries 1--4). This modification was performed without any
prolonged heating. To our delight, this problem could be
solved by adding 0.05 equiv of tetrabutylammonium hy-
drogenosulfate (phase-transfer catalyst).13 Under these con-
ditions, the reactions could be performed at the 10–30 g
scale without any difficulty (entries 5 and 6). Moreover, un-
der the conditions summarized in Table 1, entries 6 and 10,
the product could be obtained by precipitation from aceto-
nitrile as a true click procedure avoiding even the use of an
extraction solvent. For other examples depicted in the Table
1, the DMSO or MeCN conditions were used interchange-
ably.
negative impact on the yields. Notably, the S Ar reaction
N
could be monitored by NMR spectroscopy and/or TLC and
proceeded to completion in less than 45 min at room tem-
perature. In most cases, the reactions could also be followed
visually by observing the disappearance of crystalline sodi-
um azide (replaced by floculent sodium fluoride). Then,
phenylacetaldehyde was added and, upon the subsequent
addition of DBU, the temperature of the reaction mixture
rose typically to above 50 °C due to the rapid and exother-
mic cycloaddition step. The latter was complete in less than
Another pitfall avoided by the organo-click strategy is il-
lustrated in Table 1, entry 7. Indeed, it has been shown that
2-nitroaryl azides display limited stability towards the for-
mation of azide-nitro cycloadducts.16 While performing
this work, we noted that this undesired reaction is strongly
dependent on the substituents. In the case of entry 7, the
compound could be obtained albeit with a moderate yield
by azide-enolate cycloaddition, while the slower and higher
30 minutes, as was reported by Ramachary et al. for a pre-
formed azide. For comparison with CuAAC, for the same
product we completely failed to reproduce the use of
0
8d
FeCl /Cu as a catalytic system (probably due to the sensi-
3
tivity of these heterogeneous conditions to the granulome-
try of solid reagents) and we obtained underwhelming re-
8
c
8c
17
sults by using the protocol described by Ramana et al.
(
temperature CuAAC resulted in full degradation. Under
the same conditions, other compounds bearing halide sub-
stituents could be obtained without modifications of the
synthetic procedure (entries 8–10).
2+
Cu , sodium ascorbate in DMSO). Only with modifications
were we able to obtain the desired product and at the ex-
pense of tedious recrystallizations.6 In particular, the most
problematic impurity was a yellow compound, likely a cop-
b
We then switched to 2-nitroaryl fluorides bearing elec-
tron-donating groups as starting materials. As could be ex-
11
per(I) acetylide complex (colored impurity of special con-
cern given the objective of our project).
pected, the S Ar reaction proceeded rather slowly and re-
N
1
quired moderate heating of the reaction mixture. H NMR
F
N3
spectroscopy could be used to check the progress of the re-
action (see an example of NMR survey in the Supporting In-
formation) in order to ensure that the reagents for the cyc-
loaddition step are only added after full conversion of the
starting fluoride to the required aryl azide intermediate.
These precautions taken into account, the results shown in
Table 1, entries 11–14, highlight the compatibility of this
strategy with substrates bearing electron-donating groups.
In the case of the methoxy-substituted substrate shown in
entry 12, more drastic conditions were required (including
for the cycloaddition step, see Supporting Information), and
in the case of entry 14 the low yield is tentatively attributed
to the steric effect of the methyl group and/or to difficult
crystallization.
NaN3
DMSO or
NO2
NO2
X
MeCN, NBu4HSO4
X
N
N
phenylacetaldehyde
DBU
N
NO2
X
Scheme 2 Azide-enolate cycloaddition performed on unisolated
-nitrophenyl azides arising from S Ar
2
N
The experiments summarized in Table 1, entries 1-4
and more generally, all reactions described in Table 1)
were performed on gram scale and the products were ob-
(
12
tained by simple work-up (extractions and recrystalliza-
tions, see the Supporting Information). Nevertheless, we
were interested in the scale-up of these syntheses, especial-
ly for those compounds that are amenable to divergent
functionalization in further synthetic steps; for example,
sulfonation of the aromatic ring (unsubstituted compound)
or cross-couplings (Br-substituted compound). Unfortu-
nately, when the reactions were performed on larger scale
The aforementioned set of results allows us to under-
take the syntheses of several fluorescent compounds. This
work is currently ongoing and the results will be reported
in due course.
However, all examples of the S Ar–organo-click se-
N
quence deal with 4-phenyl substituted triazoles. Substitut-
ed derivatives of phenylacetaldehyde might be rather ex-
pensive and/or difficult to prepare. To diversify the com-
pound library, we sought to design a Sonogashira-CuAAC
reaction relying on an unisolated 2-nitroaryl azide interme-
(
10–30 g of product) we noted that removal of traces of
high-boiling DMSO was problematic and time-consuming.
Hence, we sought to change the reaction medium. To this
end, acetonitrile, which has a much lower boiling point, was
selected as an alternative polar aprotic solvent. However, no
SNAr reaction could be observed in this solvent even after
diate obtained by S Ar. Interestingly, in the report by
N
Friscourt and Boons, exogenous fluoride is added to depro-
tect a TMS-alkyne after a Sonogashira reaction.1 In our
0
case, fluoride ion is a by-product of the S Ar reaction. We
N
©
2019. Thieme. All rights reserved. Synlett 2019, 30, A–E

C
Synlett
A. Roux, F. Cisnetti
Cluster
Table 1 Compounds Obtained by Azide-Enolate Cycloaddition
Entry
1
2-Nitroaryl fluoride reagent
Solvent
DMSO
Phenylacetaldehyde (equiv)
1.5
Temp (°C)
RT
Duration of S
N
Ar (min) Yield (%)a
876b
F
<45
NO2
F
2
3
4
5
6
7
8
9
DMSO
DMSO
DMSO
MeCNc
MeCNc
DMSO
DMSO
DMSO
MeCN
MeCN
DMSO
1.1
1.5
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
RT
RT
RT
50
50
RT
RT
RT
50
50
100
<45
<45
<45
<2
85b
NO2
F
886b
90b
Br
Br
NO2
F
NO2
F
78
NO2
82d
F
<2
Br
NO2
F
<45
<60
<90
<2 h
4.5 h
18 h
45
F3C
NO2
9114
72
F
Cl
Cl
NO2
F
NO2
10
11
12
F
90 (80)d,15
I
NO2
MeO
F
92
NO2
F
45
NO2
OMe
1
3
4
MeCN
DMSO
1.1
1.1
50
80
2 h
25
65
F
NO2
1
1.5 h
F
I
NO2
a
b
c
Isolated yield, purification by extraction and recrystallization.
6b
By applying the described procedure with the only change being the reduction of the excess of phenylacetaldehyde.
In the presence of tetrabutylammonium hydrogen sulfate (0.05 equiv).
Purification by precipitation in water.
d
©
2019. Thieme. All rights reserved. Synlett 2019, 30, A–E

D
Synlett
A. Roux, F. Cisnetti
Cluster
I
SiMe3
PdCl2(PPh3)2
TEA, CuI, THF
+
SiMe3
EWG
X
EWG = COOMe, CN
EWG
N
N
N
F
NaN , DMSO
X
N3
X
EWG
3
+
F
CuI
NO2
NO2
NO2
X = Br, Cl, H
X = Cl, EWG = COOMe: 62%
X = Br, EWG = COOMe: 73%
X = H, EWG = CN: 60%
Scheme 3 Sonogashira coupling, desilylation/S Ar, CuAAC four-step reaction sequence performed without isolation of any intermediate
N
were able to show that this strategy is indeed feasible in
some cases (Scheme 3). To this end, a Sonogashira reaction
on an aryl iodide with TMS-acetylene was performed under
standard conditions [Pd(PPh ) Cl (0.4 mol%), CuI (0.4
References
(
1) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed.
001, 40, 2004.
2
3
2
2
(
2) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem. Int. Ed. 2002, 41, 2596. (b) Tornoe, C. W.;
Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057. For
recent reviews see: (c) Haldón, E.; Nicasio, M. C.; Pérez, P. J. Org.
Biomol. Chem. 2015, 13, 9528. (d) Wang, C. L.; Ikhlef, D.; Kahlal,
S.; Saillard, J. Y.; Astruc, D. Coord. Chem. Rev. 2016, 316, 1.
3) (a) McKay, C. S.; Finn, M. G. Chem. Biol. 2014, 21, 1075. (b) Tang,
W.; Becker, M. L. Chem. Soc. Rev. 2014, 43, 7013. (c) Tiwari, V. K.;
Mishra, B. B.; Mishra, K. B.; Mishra, N.; Singh, A. S.; Chen, X.
Chem. Rev. 2016, 116, 3086.
18
mol%)]. In parallel, an S Ar reaction was performed on a
N
2-nitrophenyl azide. Upon completion of both reactions,
the two separate reaction mixtures were mixed and a fur-
ther amount of CuI was added. After a few hours of moder-
ate heating, the product was obtained by extraction and re-
(
crystallization. Remarkably, four distinct reactions (S Ar,
N
Sonogashira coupling, TMS deprotection, CuAAC) occurred.
Unfortunately, this approach was not general and appears
to be restricted to aryl iodides bearing electron-withdraw-
ing groups (ester, CN), as evidenced by the complete failure
of a reaction using electron-rich 2-iodoanisole.
(4) (a) Bonandi, E.; Christodoulou, M. S.; Fumagalli, G.; Perdicchia,
D.; Rastelli, G.; Passarella, D. Drug Discovery Today 2017, 22,
1572. (b) Dheer, D.; Singh, V.; Shankar, R. Bioorg. Chem. 2017,
71, 3.
In summary we have reported synthetically efficient
(
5) (a) Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem.
Int. Ed. 2005, 44, 5188. (b) For example, see: Odlo, K.; Høydahl,
E. A.; Hanse, T. V. Tetrahedron Lett. 2007, 48, 2097.
procedures to access 1,2,3-triazoles arising from an S Ar-
N
cycloaddition sequence without isolating an intermediate
aryl azide. Given the interest in 1,4-diaryl triazoles in areas
(6) (a) Fauché, K.; Nauton, L.; Jouffret, L.; Cisnetti, F.; Gautier, A.
Chem. Commun. 2017, 53, 2402. (b) Bouchemella, K.; Fauché, K.;
Anak, B.; Jouffret, L.; Bencharif, M.; Cisnetti, F. New J. Chem.
4
such as medicinal chemistry, this report is a modest con-
tribution to the arsenal of procedures that allow safe and
straightforward access to this useful class of compounds.
Future extensions of this study may also include the use of
enolizable arylacetones and deoxybenzoins.1
2018, 42, 18969.
(7) Srinivas, D.; Ghule, V. D.; Tewari, S. P.; Muralidharan, K. Chem.
Eur. J. 2012, 18, 15031.
9
(
8) S Ar: (a) Ramana, C. V.; Goriya, Y.; Durugkar, K. A.; Chatterjee,
N
S.; Krishnaswamy, S.; Gonnade, R. G. CrystEngComm 2013, 15,
5
283. (b) Ramana, C. V.; Chatterjee, S.; Durugkar, K. A.;
Funding Information
Gonnade, R. G. CrystEngComm 2009, 11, 143. (c) Dururgkar, K.
A.; Gonnade, R. G.; Ramana, C. V. Tetrahedron 2009, 65, 3974.
The Centre National de la Recherche Scientifique (CNRS; Emer-
gence@INC 2019 programme, Fluoclick project) is acknowledged for
funding.()
(d) Saha, B.; Sharma, S.; Sawant, D.; Kundu, B. Tetrahedron 2008,
64, 8676. (e) Saha, B.; Sharma, S.; Sawant, D.; Kundu, B. Synlett
2
007, 1591. (f) Metal-catalyzed: Andersen, J.; Bolvig, S.; Liang,
X. Synlett 2005, 2941.
(
9) Ramachary, D. B.; Shashank, A. B.; Karthik, S. Angew. Chem. Int.
Acknowledgment
Ed. 2014, 53, 10420.
(
10) (a) Friscourt, F.; Boons, G. J. Org. Lett. 2010, 12, 4936. (b) Israr,
M.; Ye, C.; Muhammad, M. T.; Li, Y.; Bao, H. Beilstein J. Org.
Chem. 2018, 14, 2916; and references cited therein.
Léa Berthelier, Mélanie Antoine, Camille Lassalas, and Marianne
Kerleaux are acknowledged for participating in this project through
short undergraduate training periods.
(11) Buckley, B.; Dann, S.; Heaney, H. Chem. Eur. J. 2010, 16, 6278.
12) General Procedure (DMSO): 2-Nitroaryl fluoride reagent was
(
Supporting Information
dissolved in DMSO (ca. 1 mL per mmol), then NaN (1.1 equiv)
3
was added. The solution was either heated or stirred at room
temperature until completion of the aromatic nucleophilic sub-
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691524.
1
S
u
p
p
orti
n
g Inform ati
o
n
S
u
p
p
orit
n
g Inform ati
o
n
stitution (either followed by TLC or H NMR). After cooling to
room temperature, phenylacetaldehyde (0.9 equiv) and DBU
(0.09 equiv) were subsequently added. The mixture was stirred
©
2019. Thieme. All rights reserved. Synlett 2019, 30, A–E

E
Synlett
A. Roux, F. Cisnetti
Cluster
either at room temperature or heated until completion of the
reaction (followed by TLC). CH Cl was then added to the solu-
tion, and the organic phase was washed with a saturated
(CH ), 128.5 (Cq ), 128.5 (Cq ), 129.1 (CH ), 129.7 (Cq ), 133.5
ar
ar
ar
ar
ar
(CH ), 142.8 (CH ), 144.1 (Cq
), 147.2 (CH ). HRMS (ESI):
2
2
ar
ar
triazole
ar
+
m/z [M + H] calcd for C14H10IN O : 392.9843; found: 392.9840.
4 2
aqueous solution of NH Cl. The aqueous phase was then
(14) Previously reported (small-scale preparation): Jia, Z.; Zhu, Q.
Bioorg. Med. Chem. Lett. 2010, 20, 6222.
4
extracted with CH Cl and the combined organic phases were
2
2
washed with water, brine, dried over MgSO , and the solvent
(15) Previously reported (61% yield) in reference 8c.
4
was evaporated under reduced pressure. Recrystallization with
EtOH gave the desired product.
(16) Ghosh, P. B.; Ternai, B.; Whitehouse, M. W. J. Med. Chem. 1972,
15, 255.
Analytical data for a representative compound obtained by this
procedure: 1-(5-Chloro-2-nitrophenyl)-4-phenyl-1H-1,2,3-tri-
(17) As evidenced by a dangerous massive gaseous evolution we
observed while performing an experiment related to entry 7
under the conditions described by Ramana et al. in reference 8c.
(18) General procedure (Sonogashira click): In a first round-
bottom flask, iodophenyl starting material was dissolved in THF
(10 mL per 4 mmol). Ethynyltrimethylsilane (1.1 equiv), tri-
ethylamine (4 equiv), PdCl (PPh ) (0.4 mol%), and CuI (0.4
1
azole. H NMR (500 MHz, DMSO-d ):  = 7.36–7.44 (m, 1 H, H ),
6
Ar
7
.51 (t, J = 7.5 Hz, 2 H, H ), 7.93 (d, J = 7.5 Hz, 2 H, H ), 8.02 (d,
A
r
A
r
J = 8.5 Hz, 1 H, H ), 8.10 (dd, J = 8.5, 2.2 Hz, 1 H, H ), 8.43 (d,
Ar
Ar
13
J = 2.2 Hz, 1 H, H ), 9.18 (s, 1 H, Htriazole). C NMR (126 MHz,
Ar
DMSO-d ):  = 122.7 (CH ), 125.4 (CH ), 125.6 (CH ), 127.8
6
Ar
Ar
Ar
2
3 2
(
1
Cq ), 128.5 (CH ), 128.7 (CH ), 129.1 (CH ), 129.7 (Cq ),
mol%) were then added, and the mixture was stirred at 50 °C
until completion of the Sonogashira reaction. In a second
round-bottom flask, fluoronitrobenzene starting material (1.05
equiv) was dissolved in MeCN (10 mL per 4 mmol). Sodium
azide (1.15 equiv) and tetrabutylammonium hydrogensulfate
(0.05 equiv) were then added and the mixture was stirred at
50 °C until completion of the aromatic nucleophilic substitution
reaction. The first round-bottom flask was then filtrated, and
the filtrate was poured into the second round-bottom flask. CuI
(8 mol%) was finally added, and the resulting mixture was
stirred at 60 °C until completion of both the deprotection and
click reaction. The resulting solution was then filtered over
Celite, and the filtrate was evaporated under reduced pressure.
Recrystallization with EtOH was performed to obtain the
desired product.
Ar
Ar
Ar
Ar
Ar
34.2 (CH ), 135.1 (Cq ), 144.3 (Cq
), 147.2 (Cq ). HRMS
Ar
Ar
triazole Ar
+
(ESI): m/z [M + H] calcd for C14H10ClN O : 301.0487; found:
4 2
3
01.0482.
(
13) General procedure (acetonitrile): 2-Nitroaryl fluoride reagent
was dissolved in MeCN (ca. 1 mL per mmol), then NaN3 (1.1
equiv) and tetrabutylammonium hydrogensulfate (0.1 g per
gram of starting material) were added. The solution was either
heated or stirred at room temperature until completion of the
1
aromatic nucleophilic substitution (either followed by TLC or H
NMR). After cooling to room temperature, phenylacetaldehyde
(0.9 equiv) and DBU (0.09 equiv) were added. The mixture was
stirred either at room temperature or heated to 80 °C until com-
pletion of the reaction (followed by TLC). Either work-up 1 or 2
were used.
Work-up 1 (gram-scale): as described in reference 12.
Work-up 2 (Table 1, entries 6, 10; 10–30 g scale): a massive pre-
cipitate was observed. The solid was isolated by filtration and
washed with a minimal amount of cold (0 °C) acetonitrile and
several times with water. After desiccation, the solid was
obtained in pure form.
Analytical data for a representative compound obtained by this
procedure: Methyl 4-[1-(5-chloro-2-nitrophenyl)-1H-1,2,3-
1
triazol-4-yl]benzoate: H NMR (400 MHz, DMSO-d ):  = 3.88
6
(s., 3 H, CH ), 7.85–8.08 (overlapping signals, 5 H, H ), 8.18–
3
Ar
13
8.39 (overlapping signals, 2 H, H ), 9.36 (s, 1 H, Htriazole).
C
Ar
NMR (126 MHz, DMSO-d ):  = 52.0 (CH ), 124.0 (CH, C ), 125.3
6
3
Ar
Analytical data for a representative compound obtained by this
(CH, C ), 127.2 (CH, C ), 127.2 (CH, C ), 129.1 (Cq, C ), 129.8
Ar Ar Ar Ar
procedure:
1-(4-Iodo-2-nitrophenyl)-4-phenyl-1H-1,2,3-tri-
(Cq, C ), 129.9 (CH, C ), 131.0 (CH, C ), 134.0 (Cq, C ), 138.4
Ar Ar Ar Ar
1
azole. H NMR (400 MHz, DMSO-d ):  = 7.35–7.45 (m, 1 H, H ),
(Cq, C ), 142.4 (Cq, C
), 145.8 (Cq, C ), 165.7 (Cq, C=O).
6
ar
Ar
triazole
+
Ar
7.46–7.55 (m, 2 H, H ), 7.74 (d, J = 8.3 Hz, 1 H, H ), 7.93 (d,
HRMS (ESI): m/z [M + H] calcd for C16H12N O Cl: 359.0542;
ar
ar
4 4
J = 7.2 Hz, 2 H, H ), 8.36 (dd, J = 8.3, 1.7 Hz, 1 H, H ), 8.58 (d,
found: 359.0532.
ar
ar
13
J = 1.6 Hz, 1 H, H ), 9.17 (s, 1 H, Htriazole). C NMR (100 MHz,
(19) Shashank, A. B.; Karthik, S.; Madhavachary, R.; Ramachary, D. B.
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DMSO-d ):  = 96.4 (Cq -I), 122.5 (CH ), 125.4 (CHtriazole), 128.4
Chem. Eur. J. 2014, 16877.
6
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2019. Thieme. All rights reserved. Synlett 2019, 30, A–E