Potassium tert -Butoxide Promoted Synthesis of 4,5-Diaryl-2 H -1,2,3-triazoles from Tosylhydrazones and Nitriles

Article abstract of DOI:10.1055/s-0040-1707321

Intermolecular cycloaddition of tosylhydrazones with nitriles was investigated. t -BuOK was shown to be an excellent base for increasing the effectiveness of the reaction in this protocol, and homocoupling of the tosylhydrazones was significantly inhibited by using xylene as a solvent. Through this transformation, a variety of 4,5-diaryl-2 H -1,2,3-triazoles were prepared in good to excellent yields and with high purities. The process is azide-free and transition-metal-free.

Full text of DOI:10.1055/s-0040-1707321

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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 31, A–E
letter
A
en
S. Qiu et al.
Letter
Synlett
Potassium tert-Butoxide Promoted Synthesis of 4,5-Diaryl-2H-
1,2,3-triazoles from Tosylhydrazones and Nitriles
Shanguang Qiu
Yuxue Chen
Xinming Song
Li Liu
H
N
NNHTs
t-BuOK
N
N
R2CN
+
R1
xylene, 90 °C
R1
R2
R1 = (het)aryl
R2 = (het)aryl
azide-free and transition-metal-free
gram-scale synthesis
up to 98% yield with high purity
homocoupling inhibited
Xi Liu
Luyong Wu*
Key Laboratory of Tropical Medicinal Resource Chemistry of
Ministry of Education, Hainan Normal University, No. 99,
Longkun South Road, Haikou 571158, P. R. of China
wuluyong@hainnu.edu.cn
Corresponding Author
Received: 24.07.2020
Accepted after revision: 14.09.2020
Published online: 12.10.2020
Generally, 4,5-diaryl-NH-1,2,3-triazoles have been syn-
thesized by [3+2]-cycloaddition of diarylalkynes with
trimethylsilyl azide7 or sodium azide8 (Scheme 1a). Because
of the potential explosivity and toxicity of azides,9 the con-
cept of azide-free synthesis has been widely adopted in the
synthesis of 1,2,3-triazoles.10 This progress has also influ-
enced the synthesis of NH-1,2,3-triazoles.11 It is therefore
imperative to explore azide-free protocols for the synthesis
of 4,5-diaryl-1,2,3-triazoles. In 1988, Grundon and Khan re-
ported that the reactions of aryldiazomethanes with arylal-
dehyde azines or aryl nitriles gave the corresponding 4,5-
diaryl-NH-1,2,3-triazoles in moderate yields (Scheme 1b).12
Perhaps, the instability, hazardous nature, and difficulty in
handling of diazo compounds has restricted the use of this
cycloaddition reaction and, consequently, this work is rare-
ly mentioned in the literature on 1,2,3-triazoles.
DOI: 10.1055/s-0040-1707321; Art ID: st-2020-l0415-l
Abstract Intermolecular cycloaddition of tosylhydrazones with ni-
triles was investigated. t-BuOK was shown to be an excellent base for
increasing the effectiveness of the reaction in this protocol, and homo-
coupling of the tosylhydrazones was significantly inhibited by using xy-
lene as a solvent. Through this transformation, a variety of 4,5-diaryl-
2H-1,2,3-triazoles were prepared in good to excellent yields and with
high purities. The process is azide-free and transition-metal-free.
Key words triazoles, tosylhydrazones, cycloaddition, potassium bu-
toxide
NH-1,2,3-Triazoles, as a class of special 1,2,3-triazoles,
are found in a number of bioactive molecules (for examples,
see Figure 1).1 Consequently, their synthesis has become an
important issue in 1,2,3-triazole chemistry and medicinal
chemistry.2 Since the discovery of the copper-catalyzed
Huisgen cycloaddition of azides and alkynes for the synthesis
of 1,2,3-triazoles with exclusive regioselectivity and high
efficiency,3 several elegant protocols have been used to pre-
pare NH-1,2,3-triazoles from azides through cycloaddition
reactions of azides,4 multicomponent reactions,5 and other
reactions.6 Although various NH-1,2,3-triazole motifs have
been synthesized, 4,5-diaryl-NH-1,2,3-triazoles have re-
ceived little attention.
a) Cycloaddition of azides with alkynes or substituted alkenes
NC
Ar2
Ar1
Ar2
N
Ar1
Ar1
+
TMSN3 or NaN3
N
or
N
H
Ar2
b) Cyclization of aryldiazomethanes with nitriles or azines
Ar1
Ar2
N2
CN
or
t-BuOK
N
+
N
N
Ar1
Ar2HCN NCHAr2
N
H
Ar2
c) Homo- and heterocoupling of N-tosylhydrazones
Ar1
Ar2
NNHTs
NNHTs
I
N
Cs2CO3
N
N
+
N
S
N
Ar2
Ar1
NH
N
NH
N
H
DMF
H3CO
H3CO
O
S
O
d) This work: intermolecular reaction of N-tosylhydrazones with nitriles
O
N
H
Ar1
OCH3
N
N
HN
NNHTs
t-BuOK
N
Ar2
N
OCH3
+
CN
Ar1
Ar2
N
H
breast cancer cell inhibitor
VIM-2b-lactamase Inhibitor
(CA-4) analogue
Figure 1 Bioactive molecules containing NH-1,2,3-triazole structures
Scheme 1 Synthetic approaches to 4,5-diaryl-NH-1,2,3-triazoles
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
S. Qiu et al.
Letter
Synlett
In recent decades, tosylhydrazones have attracted in-
tense interest from the organic-synthesis community,4d,5b,13
and they have been widely used in many reactions as excel-
lent and safe precursors of diazo compounds.14 Further-
more, the use of tosylhydrazones as versatile synthons has
been explored in many novel reactions to afford various
heterocycles, including 1,2,3-triazoles.15 Recently, the
groups of Sakač and Mani reported a synthesis of NH-1,2,3-
triazoles through 1,3-dipolar cycloadditions of diazo com-
pounds generated in situ from tosylhydrazones.16 Obvious-
ly, the preparation of 4,5-diaryl-NH-1,2,3-triazoles by 1,3-
dipolar cycloadditions of nitriles with diazo compounds
generated in situ from tosylhydrazones would constitute an
elegant protocol.
In 2017, the group of Maity and Manna described regio-
selective syntheses of 1,2,3-triazoles and pyrazoles from
tosylhydrazones.17 They succeeded in synthesizing 4,5-dia-
ryl-NH-1,2,3-triazoles in moderate to good yields by cou-
pling tosylhydrazones. They also showed that the electronic
nature of tosylhydrazone influenced the coupling process.
As the results, when cross-couplings of different tosylhy-
drazones were carried out, the corresponding homocoupled
NH-triazoles were obtained as byproducts and reduced the
purity of the desired products. The authors also explored
the intermolecular reactions of tosylhydrazones with ni-
triles to provide two 4,5-diaryl-NH-1,2,3-triazoles,17 in
which homocoupling of the tosylhydrazones similarly de-
creased the yields and the purities of the products (Scheme
1c).17 The challenge therefore remained of inhibiting the
homocoupling cyclization of tosylhydrazones to provide
4,5-diaryl-NH-1,2,3-triazoles with high efficiency and high
purity. Because of our continuing interest in 1,2,3-tri-
azoles,18 we decide to explore further the azide-free reac-
tion of tosylhydrazones with nitriles (Scheme 1d).
suitable as a base in intramolecular cycloadditions,16 did
not facilitate the intermolecular reaction. However, when
2.0 equivalents of t-BuOK were used as the base, the desired
product was isolated in 38% yield, along with benzaldehyde
azine19 as a byproduct in a yield of 35% (entry 3). Encour-
aged by this result, and with the aim of restraining the for-
mation of the benzaldehyde azine byproduct, we increased
the amount of t-BuOK to 3.0 equivalents, and this gave the
desired product in an excellent yield of 90%. Cs2CO3 as a
base gave a lower yield of 30%. When we screened other
H
N
NNHTs
N
N
t-BuOK (3 equiv)
+
ArCN
xylene, 90 °C
Ar
1a
2a–t
3a–t
H
N
N
H
H
N
H
N
N
N
N
N
N
N
N
N
CF3
OCH3
3a 90%
3b 93% (98.2%)
3d 96% (99.8%)
3c 98%
H
N
H
H
N
H
N
N
N
N
N
N
N
N
N
N
Br
CF3
Br
Br
3e 95% (99.5%)
3f 89% (98.1%)
3g 96% (98.9%)
3h 98% (99.3%)
H
N
H
N
H
N
H
N
N
N
N
N
N
N
N
N
Cl
Cl
Cl
Cl
Cl
Cl
Initially, we chose benzaldehyde tosylhydrazone (1a)
and benzonitrile (2a) as model substrates for the optimiza-
tion of the reaction conditions (Table 1). K2CO3, generally
3j 96% (99.3%)
3k 86% (97.9%)
3i 97% (99.7%)
3l 94% (99.8%)
H
N
H
N
H
N
H
N
N
N
N
N
N
N
N
N
Table 1 Optimization of the Intermolecular Cyclizationa
S
N
CO2CH3
H
N
3m 68% (93.4%)
3n 82% (99.5%)
3o 96% (100.0%)
3p 40% (92.9%)
NNHTs
base
N
N
+
PhCN
H
N
solvent, temp
H
N
Ph
H
N
H
N
Ph
Ph
N
N
N
N
1a
2a
3a
N
N
N
N
Bn
Entry
Base (equiv)
Yieldb (%)
OH
NH2
1
2
3
4
5
K2CO3 (2.0)
DBU (2.0)
n.d.
n.d.
38
3q N.R.
3r N.R.
3s N.R.
3t N.R.
Scheme 2 Reactions of benzaldehyde tosylhydrazone (1a) with various
nitriles under the optimized conditions. Reaction conditions: 1a (1.0
mmol), 2 (1.2 mmol), xylene (6 mL), 90 °C, 4 h. The yields of the cross-
coupling products were calculated from the combined isolated yields of
the mixtures of the homocoupled 1,2,3-triazole and the cross-coupled
1,2,3-triazole. The figures in parentheses are the purities of the cross-
coupled 1,2,3-triazole, determined by reverse-phase HPLC. N.R. = No
reaction.
t-BuOK (2.0)
Cs2CO3 (3.0)
t-BuOK (3.0)
30
90
a Reaction conditions: 1a (1.0 mmol), 2a (1.2 mmol), DMF (6 mL), 90 °C, 4
h, under Ar.
b Isolated yield; n.d. = not detected.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

C
S. Qiu et al.
Letter
Synlett
bases (see Supporting Information), we found that the use
of t-BuOK as a strong base is critical in improving the effi-
ciency of this intermolecular reaction.
Table 2 Optimization of the Inhibition of Homocoupling of the N-To-
sylhydrazonea
H
N
H
Having increased the efficiency of the intermolecular
reaction of the tosylhydrazone and nitrile, we turned our
interest to the inhibition of the homocoupling of the tosyl-
hydrazone. When the reaction of benzaldehyde tosylhydra-
zone (1a) and 4-methylbenzonitrile 2b was carried out, the
4,5-diphenyl- 2H-1,2,3-triazole (3a) homocoupling byprod-
uct could not be separated from the desired product 3b by
flash column chromatography on silica gel. When DMF was
used as the solvent, the isolated product contained 6.1% of
homocoupling product. When toluene or xylene was used,
however, the proportion of 3a (as determined by HPLC) was
significantly reduced, and xylene was found to give the best
result in terms of the yield and the selectivity. We surmised
that, in comparison with Cs2CO3, the greater basicity of t-
BuOK is a critical factor in relation to the deprotonation of
the tosylhydrazone to transfer anions or diazo compounds,
thereby markedly inhibiting the homocoupling of the tosyl-
hydrazone. Therefore the optimal reaction conditions are:
tosylhydrazone (1.0 mmol), nitrile (1.2 mmol), t-BuOK (3.0
mmol) for four hours at 90 °C under an Ar atmosphere.
N
N
N
N
NNHTs
+
N
CN
t-BuOK
+
solvent, 110 °C
CH3
cross-coupling
1a
2b
3a
3b
homocoupling
Entry
Solvent
Yieldb of 3b (%)
3a/3bc
1
2
3
DMF
90
93
93
6.1: 93.9
0.7: 99.3
0.5: 99.5
toluene
xylene
a Reaction conditions: 1a (1.0 mmol), 2b (1.2 mmol), solvent (6 mL), 4 h,
under Ar.
b Based on the isolated mixture of 3a and 3b.
c Determined by HPLC.
With these optimized conditions in hand, we extended
the scope of the method to the reactions of 1a with various
nitriles 2 (Scheme 2). The intermolecular cyclization reac-
tion was found to tolerate various substituents on the aryl
nitrile 2, and gave the desired products 3a–o in good to ex-
H
N
NNHTs
t-BuOK (3 equiv)
N
N
+
R2CN
xylene, 90 °C
R1
R1
R2
1
2
4a–ag
H
H
N
H
H
N
N
N
N
N
N
N
N
N
N
N
R1
R2
R2
R2
R2 = o-CH3C6H4, 4l 82%
R2 = p-CH3C6H4, 4m 97% (98.7%)
R2 = p-CH3OC6H4, 4n 87%
R1 = p-CH3C6H4, 4a 92% (98.5%)
R1 = p-CH3OC6H4, 4b 91%
R1 = p-CF3C6H4, 4c 90% (100.0%)
R1 = p-ClC6H4, 4d 98% (97.2%)
R2 = p-CH3C6H4, 4e 77%
R2 = m-CH3C6H4, 4i 98%
R2 = o-CH3C6H4, 4j 96% (97.8%)
R2 = 3,5-diClC6H3, 4k 93% (100.0%)
R2 = m-CH3C6H4, 4f 98% (100.0%)
R2 = o-CH3C6H4, 4g 97% (99.3%)
R2 = p-ClC6H4, 4h 98% (99.4%)
H
N
H
N
H
N
H
N
N
N
N
N
N
N
N
N
H3CO
R2
R2
R2
R2
Br
R2 = p-BrC6H4, 4s 97%
R2 = p-CH3C6H4, 4t 98% (97.4%)
R2 = o-BrC6H4, 4u 67% (98.5%)
Cl
Br
R2 = o-CH3OC6H4, 4o 84%
R2 = p-ClC6H4, 4p 82%
R2 = m-BrC6H4, 4q 90%
R
2 = p-ClC6H4, 4v 96%
R2 = o-CH3OC6H4, 4w 94% (100.0%)
R2 = p-CH3C6H4, 4r 95% (97.8%)
H
N
H
N
H
N
H
H
N
N
N
O
N
N
N
N
N
N
N
N
S
N
Br
R2
H3CO
OCH3
N
F3C
CF3
R2 = 2-thienyl, 4aa 76%
R2 = p-CH3C6H4, 4ab 63% (98.6%)
4ac 87%
4x 93%
4y 83%
4z 82%
Scheme 3 Reaction scope of tosylhydrazones 1 with nitriles 2 under the optimized conditions. Reaction conditions: 1a (1.0 mmol), 2 (1.2 mmol), xylene
(6 mL), 90 °C, 4 h, under Ar. The yields of the cross-coupling products were calculated from the combined isolated yields of the mixtures of the homo-
coupled 1,2,3-triazole and the cross-coupled 1,2,3-triazole. The figures in parentheses are the purities of the cross-coupled 1,2,3-triazole, determined
by reverse-phase HPLC.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

D
S. Qiu et al.
Letter
Synlett
cellent yields of 68–98%; however, the methoxycarbonyl-
substituted product 3p was obtained in only 40% yield. Only
small amounts of the corresponding homocoupling prod-
ucts of the tosylhydrazones were formed, and the cross-
coupling products of the tosylhydrazone with the nitrile
were formed in high ratios. The yields were little affected
by the presence of electron-withdrawing or electron-donat-
ing groups on the nitriles. Moreover, the presence of steric
hindrance at the ortho-position had little effect on the
yields in this transformation (3h, 3j, and 3k). However, an
aryl nitrile bearing two methyl groups at the two ortho-po-
sitions gave the corresponding 1,2,3-triazole 3m in a lower
yield and a lower cross-coupling ratio. Heterocyclic aryl ni-
triles also worked well under optimized conditions, and
gave good yields of corresponding 1,2,3-triazoles 3n and 3o
with a high cross-coupling ratio. Unfortunately, when a hy-
droxy or amino group was present in the benzonitrile, the
desired product was not obtained and the unreacted nitrile
was recovered by column chromatography (3q, 3r). Nonaro-
matic nitriles 2s and 2t also failed to give the desired prod-
ucts 3s and 3t. When phenylacetonitrile was used, the
benzaldehyde azine was isolated.
xylene; these conditions were beneficial to intermolecular
cyclization and inhibited the homocoupling of the tosylhy-
drazone. The reaction provides an efficient and convenient
method for the synthesis of NH-1,2,3-triazoles, and a wide
range of 4,5-diaryl-2H-1,2,3-triazoles were obtained in
good to excellent yields.
Funding Information
This work was supported by the Natural Science Foundation of Hain-
an Province (219MS044) and the National Natural Science Foundation
of China (NSFC-21562019).
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Acknowledgment
We are grateful to our colleagues in the Centre for Instrumental Anal-
ysis for providing services.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707321. Su
p
p
ortingInformatio
n
Su
p
p
ortingInformatio
n
To further expand the scope of this reaction, a series of
tosylhydrazones were explored in reactions with various
nitriles under the optimized conditions (Scheme 3). Gener-
ally, the corresponding 1,2,3-triazoles were obtained in
good to excellent yields with high purities. The cyclization
was highly tolerant of various functional groups on the
benzene rings. When electron-rich or electron-deficient
phenyl tosylhydrazones reacted with benzonitrile, the
1,2,3-triazoles 4a–d were obtained in excellent yields and
high purities. The reaction also permitted the use of other
substituted benzaldehyde tosylhydrazones with substitut-
ed benzonitriles (4e–z). Additionally, hetaryl aldehyde to-
sylhydrazones were also well tolerated, affording corre-
sponding 1,2,3-triazoles 4aa–ac in good yields.
References and Notes
(1) (a) Weide, T.; Saldanha, S. A.; Minond, D.; Spicer, T. P.; Fotsing, J.
R.; Spaargaren, M.; Frère, J.-M.; Bebrone, C.; Sharpless, K. B.;
Hodder, P. S.; Fokin, V. V. ACS Med. Chem. Lett. 2010, 1, 150.
(b) Madadi, N. R.; Penthala, N. R.; Howk, K.; Ketkar, A.; Eoff, R. L.;
Borrelli, M. J.; Crooks, P. A. Eur. J. Med. Chem. 2015, 103, 123.
(c) Cheng, Z.-Y.; Li, W.-J.; He, F.; Zhou, J.-M.; Zhu, X.-F. Bioorg.
Med. Chem. 2007, 15, 1533. (d) Röhrig, U. F.; Majjigapu, S. R.;
Grosdidier, A.; Bron, S.; Stroobant, V.; Pilotte, L.; Colau, D.;
Vogel, P.; Van den Eynde, B. J.; Zoete, V.; Michielin, O. J. Med.
Chem. 2012, 55, 5270. (e) Röhrig, U. F.; Awad, L.; Grosdidier, A.;
Larrieu, P.; Stroobant, V.; Colau, D.; Cerundolo, V.; Simpson, A. J.
G.; Vogel, P.; Van den Eynde, B. J.; Zoete, V.; Michielin, O. J. Med.
Chem. 2010, 53, 1172. (f) Penthala, N. R.; Madhukuri, L.;
Thakkar, S.; Madadi, N. R.; Lamture, G.; Eoff, R. L.; Crooks, P. A.
Med. Chem. Commun. 2015, 6, 1535.
(2) (a) Zhang, W.; Kuang, C.; Yang, Q. Youji Huaxue 2011, 31, 54.
(b) Tomé, A. C. In Science of Synthesis, Vol. 13; Storr, R. C.;
Gilchrist, T. L., Ed.; Thieme: Stuttgart, 2004, Chap. 13, 415.
(c) Krivopalov, V. P.; Shkurko, O. P. Russ. Chem. Rev. 2005, 74,
339.
(3) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem. Int. Ed. 2002, 41, 2596. (b) Tornøe, C. W.;
Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057.
To demonstrate the synthetic utility of the reaction, we
performed a gram-scale reaction (Scheme 4). When 1a and
2b were used as substrates, the corresponding product 3b
was isolated by column chromatography in 85% yield and a
purity of 98.4%.
H
N
N
N
NNHTs
CN
+
H3C
(4) (a) Quan, X.-J.; Ren, Z.-H.; Wang, Y.-Y.; Guan, Z.-H. Org. Lett.
2014, 16, 5728; corrigendum: Org. Lett. 2015, 17, 393. (b) Li, J.;
Wang, D.; Zhang, Y.; Li, J.; Chen, B. Org. Lett. 2009, 11, 3024.
(c) Roshandel, S.; Suri, S. C.; Marcischak, J. C.; Rasula, G.;
Prakash, G. K. S. Green Chem. 2018, 20, 3700. (d) Gao, Y.; Lam, Y.
Org. Lett. 2006, 8, 3283. (e) Augustine, J. K.; Boodappa, C.;
Venkatachaliah, S. Org. Biomol. Chem. 2014, 12, 2280.
CH3
1a
2b
3b
20 mmol
20 mmol
yield: 85%
purity: 98.4%
Scheme 4 Gram-scale reaction of 1a and 2b to give 3b
(5) (a) Wu, G.-L.; Wu, Q.-P. Synthesis 2018, 50, 2768. (b) Wu, G.-L.;
Wu, Q.-P. Adv. Synth. Catal. 2018, 360, 1949. (c) Xu, C.; Jiang, S.-
F.; Wu, Y.-D.; Jia, F.-C.; Wu, A.-X. J. Org. Chem. 2018, 83, 14802.
In summary, an intermolecular reaction of tosylhydra-
zones with nitriles is described.20 This reaction proceeded
smoothly when promoted by potassium tert-butoxide in
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

E
S. Qiu et al.
Letter
Synlett
(6) (a) Loren, J. C.; Sharpless, K. B. Synthesis 2005, 1514.
(b) Barluenga, J.; Valdés, C.; Beltrán, G.; Escribano, M.; Aznar, F.
Angew. Chem. Int. Ed. 2006, 45, 6893. (c) Zhang, H.; Tanimoto,
H.; Morimoto, T.; Nishiyama, Y.; Kakiuchi, K. Org. Lett. 2013, 15,
5222. (d) Ramachary, D. B.; Shashank, A. B. Chem. Eur. J. 2013,
19, 13175. (e) Liu, Y.; Yan, W.; Chen, Y.; Petersen, J. L.; Shi, X.
Org. Lett. 2008, 10, 5389. (f) Chai, H.; Guo, R.; Yin, W.; Cheng, L.;
Liu, R.; Chu, C. ACS Comb. Sci. 2015, 17, 147. (g) Zhang, W.;
Kuang, C.; Yang, Q. Synthesis 2010, 283.
(7) Kim, D.-K.; Kima, J.; Park, H.-J. Bioorg. Med. Chem. Lett. 2004, 14,
2401.
(8) (a) Tsai, C.-W.; Yang, S.-C.; Liu, Y.-M.; Wu, M.-J. Tetrahedron
2009, 65, 8367. (b) Madadi, N. R.; Penthala, N. R.; Song, L.;
Hendrickson, H. P.; Crooks, P. A. Tetrahedron Lett. 2014, 55,
4207.
(c) Hu, Q.; Liu, Y.; Deng, X.; Li, Y.; Chen, Y. Adv. Synth. Catal.
2016, 358, 1689. (d) Jin, T.; Kamijo, S.; Yamamoto, Y. Eur. J. Org.
Chem. 2004, 2004, 3789.
(14) Shu, W.-M.; Zhang, X.-F.; Zhang, X.-X.; Li, M.; Wang, A.-J.; Wu,
A.-X. J. Org. Chem. 2019, 84, 14919.
(15) (a) Guru, M. M.; De, S.; Dutta, S.; Koley, D.; Maji, B. Chem. Sci.
2019, 10, 7964. (b) Shen, X.; Gu, N.; Liu, P.; Ma, X.; Xie, J.; Liu, Y.;
He, L.; Dai, B. RSC Adv. 2015, 5, 63726.
(16) (a) Sakač, M. N.; Gaković, A. R.; Csanádi, J. J.; Djurendić, E. A.;
Klisurić, O.; Kojić, V.; Bogdanović, G.; Gaši, K. M. P. Tetrahedron
Lett. 2009, 50, 4107. (b) Mani, N. S.; Fitzgerald, A. E. J. Org. Chem.
2014, 79, 8889.
(17) Panda, S.; Maity, P.; Manna, D. Org. Lett. 2017, 19, 1534.
(18) (a) Wu, L.-Y.; Xie, Y.-X.; Chen, Z.-S.; Niu, Y.-N.; Liang, Y.-M.
Synlett 2009, 1453. (b) Wu, L.; Chen, Y.; Tang, M.; Song, X.; Chen,
G.; Song, X.; Lin, Q. Synlett 2012, 23, 1529. (c) Wu, L.; Chen, Y.;
Luo, J.; Sun, Q.; Peng, M.; Lin, Q. Tetrahedron Lett. 2014, 55, 3847.
(d) Wu, L.; Guo, S.; Wang, X.; Guo, Z.; Yao, G.; Lin, Q.; Wu, M. Tet-
rahedron Lett. 2015, 56, 2145. (e) Wu, L.; Wang, X.; Chen, Y.;
Huang, Q.; Lin, Q.; Wu, M. Synlett 2016, 27, 437. (f) Wu, L.; Chen,
Y.; He, W.; An, M.; Yan, G.; Fu, Q.; Chen, M. CN 108794412,
2018.
(9) (a) Chang, S.; Lamm, S. H. Int. J. Toxicol 2003, 22, 175. (b) Bräse,
S.; Banert, K. Organic Azides: Syntheses and Applications; Wiley:
Chichester, 2010.
(10) (a) van Berkel, S. S.; Brauch, S.; Gabriel, L.; Henze, M.; Stark, S.;
Vasilev, D.; Wessjohann, L. A.; Abbas, M.; Westermann, B.
Angew. Chem. Int. Ed. 2012, 51, 5343. (b) Wan, J.-P.; Hu, D.; Liu,
Y.; Sheng, S. ChemCatChem 2015, 7, 901. (c) Chen, Z.; Yan, Q.;
Liu, Z.; Xu, Y.; Zhang, Y. Angew. Chem. Int. Ed. 2013, 52, 13324.
(d) Cai, Z.-J.; Lu, X.-M.; Zi, Y.; Yang, C.; Shen, L.-J.; Li, J.; Wang, S.-
Y.; Ji, S.-J. Org. Lett. 2014, 16, 5108. (e) Liu, H.-N.; Cao, H.-Q.;
Cheung, C.-W.; Ma, J.-A. Org. Lett. 2020, 22, 1396. (f) Guru, M.
M.; Punniyamurthy, T. J. Org. Chem. 2012, 77, 5063. (g) Gu, J.;
Fang, Z.; Yang, Z.; Li, X.; Zhu, N.; Wan, L.; Wei, P.; Guo, K. RSC
Adv. 2016, 6, 89073. (h) Chen, Z.; Yan, Q.; Liu, Z.; Zhang, Y. Chem.
Eur. J. 2014, 20, 17635. (i) Wang, S.; Yang, L.-J.; Zeng, J.-L.; Zheng,
Y.; Ma, J.-A. Org. Chem. Front. 2015, 2, 1468. (j) Ahamad, S.;
Kant, R.; Mohanan, K. Org. Lett. 2016, 18, 280.
(19) Sha, Q.; Wei, Y. Tetrahedron 2013, 69, 3829.
(20) 4,5-Diaryl-2H-1,2,3-triazoles 3a–t, 4a–ag; General Procedure
A mixture of the appropriate tosylhydrazone 1 (1.0 mmol),
nitrile 2 (1.2 mmol), and t-BuOK (3.0 mmol) in xylene (6 mL)
was stirred at 90 °C for 4 h under Ar. The mixture was then
cooled to r.t. and diluted with EtOAc (40 mL). The organic layer
was washed with water (3 × 40 mL) and brine (30 mL), then
dried (Na2SO4) and filtered. The filtrate was concentrated in
vacuum, and the crude product was purified by column chro-
matography (silica gel, PE–EtOAc).
(11) He, Y.; Sun, E.; Zhao, Y.; Hai, L.; Wu, Y. Tetrahedron Lett. 2014,
55, 111.
(12) Grundon, M. F.; Khan, E. A. J. Chem. Soc., Perkin Trans. 1 1988,
2917.
(13) (a) Li, D.; Liu, L.; Tian, Y.; Ai, Y.; Tang, Z.; Sun, H.-b.; Zhang, G.
Tetrahedron 2017, 73, 3959. (b) Hu, L.; Mück-Lichtenfeld, C.;
Wang, T.; He, G.; Gao, M.; Zhao, J. Chem. Eur. J. 2016, 22, 911.
4,5-Bis(4-methoxyphenyl)-2H-1,2,3-triazole (4x)
White solid; yield: 261.3 mg (93%); mp 121.9–124.9 °C. 1H NMR
(400 MHz, CDCl3):  = 7.41 (d, J = 8.8 Hz, 4 H), 6.79 (d, J = 8.9 Hz,
4 H), 3.74 (s, 6 H). 13C NMR (100 MHz, CDCl3):  = 159.5, 140.6,
129.3, 122.2, 113.9, 55.0.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E