Palladium-Catalyzed Direct Diarylation of 2-Benzyl-1,2,3-triazole: a Simple Access to 4-Aryl- or 4,5-Diaryl-2-benzyl-1,2,3-triazoles and Phenanthro[9,10-d][1,2,3]triazoles

Article abstract of DOI:10.1002/ejoc.202100324

The reactivity of 2-benzyl-1,2,3-triazole in palladium-catalyzed direct arylation was studied. The reaction conditions for the selective synthesis of 2-benzyl-4-aryl-1,2,3-triazoles in moderate to high yields using phosphine-free Pd(OAc)₂ catalyst and inexpensive KOAc base have been found. Then, from these 4-aryl-1,2,3-triazoles, the palladium-catalyzed C?H bond functionalization of the C5-position allowed the synthesis of the corresponding 4,5-diarylated 2-benzyl-1,2,3-triazoles. This selective 4,5-diarylation of 2-benzyl-1,2,3-triazole was successfully applied for the straightforward building of the π-extended polycyclic heteroaromatic structures phenanthro[9,10-d][1,2,3]triazoles through Pd-catalyzed C4- and C5-intermolecular arylations followed by Pd-catalyzed C?H intramolecular arylation.

Full text of DOI:10.1002/ejoc.202100324

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doi.org/10.1002/ejoc.202100324
Palladium-Catalyzed Direct Diarylation of 2-Benzyl-1,2,3-
triazole: a Simple Access to 4-Aryl- or 4,5-Diaryl-2-benzyl-
1,2,3-triazoles and Phenanthro[9,10-d][1,2,3]triazoles
Xinzhe Shi,[a] Jian Zhang,[a] Thierry Roisnel,[a] Jean-François Soulé,*[a] and Henri Doucet*[a]
The reactivity of 2-benzyl-1,2,3-triazole in palladium-catalyzed
direct arylation was studied. The reaction conditions for the
selective synthesis of 2-benzyl-4-aryl-1,2,3-triazoles in moderate
to high yields using phosphine-free Pd(OAc)2 catalyst and
inexpensive KOAc base have been found. Then, from these 4-
aryl-1,2,3-triazoles, the palladium-catalyzed CÀ H bond function-
alization of the C5-position allowed the synthesis of the
corresponding 4,5-diarylated 2-benzyl-1,2,3-triazoles. This selec-
tive 4,5-diarylation of 2-benzyl-1,2,3-triazole was successfully
applied for the straightforward building of the π-extended
polycyclic heteroaromatic structures phenanthro[9,10-d][1,2,3]
triazoles through Pd-catalyzed C4- and C5-intermolecular
arylations followed by Pd-catalyzed CÀ H intramolecular aryla-
tion.
Introduction
Pd-catalyzed so-called direct arylation of 5-membered ring
heteroaromatics, via a CÀ H bond cleavage step,[1,2] has led in
recent years to a revolution in bi(hetero)aryl and poly(hetero)
aromatic synthesis methods. These couplings are very attractive,
compared to the more classical reactions catalyzed by palla-
dium such as Stille, Suzuki or Negishi couplings, because they
do not require the prior synthesis of organometallic
derivatives.[2] Several examples of Pd-catalyzed direct arylations
of various heteroarenes such as pyrazoles,[3] or imidazoles[4] with
aryl halides have been reported. A few groups have also
reported examples of Pd-catalyzed direct arylations of 1-
substituted 1,2,3-triazoles.[5] For example, in 2007, Gevorgyan
group described the first Pd-catalyzed direct arylations of 1-
benzyl- and 1-alkyl-1,2,3-triazoles.[5a] They observed a strong
preference for C5- vs C4-arylation. The same year, similar results
were reported by Oshima and Yorimitsu,[5b] for the arylation of
1-benzyl-1,2,3-triazoles using aryl chlorides under microwave
irradiation. In 2008, Ackermann’s group reported another
procedure for the C4-arylation of 1,5-disubstituted 1,2,3-
triazoles, and C5-arylation of 1,4-disubstituted 1,2,3-triazoles.[5c]
In contrast, to our knowledge, the metal-catalyzed direct
arylation of 2-substituted 1,2,3-triazoles has attracted much less
attention (Scheme 1).[6] In 2008, Fokin et al. studied the direct
arylation of a compound containing both 1-substituted 4-
phenyl-1,2,3-triazole and 2-substituted 4-phenyl-1,2,3-triazole
units (Scheme 1a).[6a] They employed Pd(PPh3)2Cl2 as the catalyst
and Bu4NOAc as the base. Their study revealed that the 1-
Scheme 1. Pd-catalyzed direct arylations of 2-substituted 1,2,3-triazoles and
1,2,3-triazole N-oxides.
substituted 4-phenyl-1,2,3-triazole unit is the most reactive,
affording the mono-arylation product in 60% yield; whereas the
diarylated compound – arylation of both types of triazole rings
– was only obtained in 24% yield.
This procedure was recently employed by Ko et al. for the
arylation of another 2-substituted 4-phenyl-1,2,3-triazole
(Scheme 1b).[6c] In 2013, in the course of their study on the
arylation of 2-substituted 1,2,3-triazole N-oxides, Kuang et al.
[a] X. Shi, J. Zhang, Dr. T. Roisnel, Dr. J.-F. Soulé, Dr. H. Doucet
ISCR-UMR 6226,
Univ Rennes,
35000 Rennes, France
E-mail: jean-francois.soule@univ-rennes1.fr
henri.doucet@univ-rennes1.fr
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attempted to arylate 2-benzyl-1,2,3-triazole with benzene under
via Pd-catalyzed intermolecular arylations followed by a CÀ H
Pd-catalyzed oxidative coupling conditions, but the reaction
was unsuccessful (Scheme 1c).[6b] A few examples of C5-
arylations of 2-substituted 1,2,3-triazole N-oxides have also
intramolecular arylation (Scheme 2).
been described (Scheme 1d).[7] However, the use of such 1,2,3- Results and Discussion
triazole N-oxides requires two more steps due to the nitrogen
protection/deprotection sequence.
4-Bromobenzonitrile (1 equiv.) and 2-benzyl-1,2,3-triazole
As the discovery of an effective procedure, for the arylation
of 1,2,3-triazole derivatives, using readily available catalyst and
base is desirable, the reactivity of 2-benzyl-1,2,3-triazole in
direct arylation in the presence of palladium catalysts needed
to be investigated. Here, we report (i) conditions for the
palladium-catalyzed direct arylation of 1,2,3-triazoles; (ii) on the
scope of the reaction; (iii) on the subsequent reactivity of these
4-aryl-1,2,3-triazoles in Pd-catalyzed CÀ H bond functionalization
for access to 4,5-diaryl-1,2,3-triazoles; and (iv) on the synthesis
of the π-extended molecules phenanthro[9,10-d][1,2,3]triazoles
(2 equiv.) were employed as model substrates for our study
(Table 1). We initially examined the influence of the base on the
aryl bromide conversion and on the selectivity (mono- vs di-
arylation) using 2 mol% Pd(OAc)2 catalyst and DMA as the
solvent. We had previously observed that this combination of
catalyst and solvent promoted very effectively the direct
arylation of some heteroarenes.[2j] Cs2CO3 was ineffective and 4-
bromobenzonitrile was recovered (Table 1, entry 1).
K2CO3 or NaOAc as bases, afforded the desired product 1a
in quite low yields due to
a partial conversion of 4-
bromobenzonitrile and also to the formation of [1,1’-biphenyl]-
4,4’-dicarbonitrile as side-product (Table 1, entries 2 and 3).
Conversely, the use of KOAc gave 1a in a high 66% yield with a
complete conversion of the aryl bromide (Table 1, entry 4). This
result is consistent with a concerted metallation deprotonation
mechanism.[8,9] CsOAc and KOPiv were found to be less effective
bases for this reaction, as 1a was obtained in 54% and 60%
yield respectively, due to a lower selectivity (mono- vs di-
arylation) (Table 1, entries 5 and 6). The use of PdCl(C3H5)(dppb)
catalyst[10] instead of Pd(OAc)2, or the reaction performed in
DMF afforded 1a in lower yields (Table 1, entries 7 and 8).
Finally, a lower catalyst loading (1 mol%) or a lower reaction
temperature led to partial conversions of 4-bromobenzonitrile
(Table 1, entries 9 and 10).
Then, 2-benzyl-1,2,3-triazole was coupled with a set of aryl
bromides in the presence of 2 mol% Pd(OAc)2, KOAc as the
base in DMA (Scheme 3). Moderate yields in the desired C4-
arylation products 2–4 were obtained using aryl bromides
Scheme 2. Pd-catalyzed direct arylation of 2-substituted 1,2,3-triazoles.
Table 1. Influence of the reaction conditions on the Pd-catalyzed C4-arylation of 2-benzyl-1,2,3-triazole with 4-bromobenzonitrile.[a]
Entry
Catalyst (mol%)
Solvent
Base
Conv. [%]
Ratio 1a:1b
Yield in 1a [%]
1
2
3
4
5
6
7
8
9
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
PdCl(C3H5)(dppb) (2)
Pd(OAc)2 (2)
Pd(OAc)2 (1)
Pd(OAc)2 (2)
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMF
DMA
DMA
Cs2CO3
K2CO3
NaOAc
KOAc
CsOAc
KOPiv
KOAc
KOAc
KOAc
KOAc
–
64
82
100
93
100
100
100
87
–
0
93:7
93:7
84:16
74:26
68:32
75:25
80:20
93:7
87:13
31
25[b]
66
54
60
45
42
55
53[c]
10
74
°
[a] Conditions: 4-Bromobenzonitrile (1 equiv.), 2-benzyl-1,2,3-triazole (2 equiv.), base (2 equiv.), 16 h, 150 C, conversion of 2-benzyl-1,2,3-triazole, isolated
°
yields. [b] A large amount of homocoupling of 4-bromobenzonitrile was also observed. [c] 120 C.
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line and 4-bromoisoquinoline also afforded the desired C4-
arylated triazole derivatives 20–23 in 51–78% yields.
The reactivity for arylation of the C5-position of 4-arylated
2-benzyl-1,2,3-triazoles was then examined (Scheme 4). As seen
in the Table 1, the 4,5-diarylation of 2-benzyl-1,2,3-triazoles
using only one equiv. of aryl bromide was generally observed in
low yield, revealing that the second arylation is challenging but
possible. The reaction of 2-benzyl-4-phenyl-1,2,3-triazole 7
(1 equiv.) with 4-bromobenzonitrile or 4-bromochlorobenzene
(2 equiv.) in the presence of 2 mol% Pd(OAc)2 catalyst afforded
the desired products 24 and 25 in 68% and 51% yield,
respectively. Lower yields in 27 and 28 were obtained from the
more electron-rich 2-benzyl-4-(4-methoxyphenyl)-1,2,3-triazole
9
using
4-bromobenzonitrile
and
4-(trifluoromethyl)
bromobenzene as the coupling partners.
The one pot synthesis of 4,5-diarylated 1,2,3-triazoles from
2-benzyl-1,2,3-triazole was then examined (Scheme 5). As
described in the Table 1, the 4,5-diarylation was generally
Scheme 3. Scope of the direct C4-arylation of 2-benzyl-1,2,3-triazole.
bearing formyl, ester or trifluoromethyl para-substituents. With
4-(trifluoromethyl)bromobenzene, a significant amount of 4,5-
diarylated triazole was observed by GC/MS and 1H NMR analysis
of the crude mixtures. Higher yields were obtained for the
coupling of the more electron-rich aryl bromides, 4-bromochlor-
obenzene, 4-bromofluorobenzene and bromobenzene leading
to products 5–7 in 74–80% yields. The structure of 7 was
confirmed by X-ray analysis.[11] tert-Butyl- and methoxy-substitu-
ents at para-position on the aryl bromides were also tolerated
giving rise to products 8 and 9 in 71% and 65% yield,
respectively. Nitrile-, formyl- and acyloxy-substituents at meta-
position on the aryl bromide were also tolerated providing the
C4-arylated triazoles 10–12 in moderate to high yields. Reac-
tions with the more hindered substrates, 2-bromobenzonitrile,
2-(trifluoromethyl)bromobenzene, 2-bromochlorobenzene and
1-bromonaphthalene were also successful affording the prod-
ucts 13–15 and 18 in 74–83% yields. Even the very congested
9-bromoanthacene was successfully coupled with 2-benzyl-
1,2,3-triazole to give 19 in 57% yield. The use of the N-
containing heterocycles, 3- or 4-bromopyridines, 3-bromoquino-
Scheme 4. Scope of the direct C5-arylation of 4-aryl-2-benzyl-1,2,3-triazoles.
Scheme 5. C4,C5-Diarylation of 2-benzyl-1,2,3-triazole.
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observed in quite low yield in the presence of 1 equiv. of aryl
attempted.[12b] However, using the reaction conditions of
Scheme 6, with 3 equiv. of base during 24 h, no trace of the
desired product was detected in the NMR of the crude mixture.
The use of 1-bromo-2-iodobenzene reagents instead of 1,2-
dibromobenzenes should allow to introduce regioselectively a
substituent on the phenanthro[9,10-d][1,2,3]triazoles, as the
oxidative addition to palladium is generally faster for the CÀ I
bond than for the CÀ Br bond. Thus, using 2-benzyl-4-(4-
(trifluoromethyl)phenyl)-1,2,3-triazole 4 and 2-bromo-4-chloro-
1-iodobenzene, we introduced of a chloro-substituent at C6-
position of the phenanthro[9,10-d][1,2,3]triazole 34 potentially
allowing for further functionalization (Scheme 7). Similarly, the
reaction of 2-benzyl-4-(4-(trifluoromethyl)phenyl)-1,2,3-triazole
4 with 2-bromo-1-iodo-4-(trifluoromethyl)benzene afforded the
symmetrical CF3-substitued phenanthro[9,10-d][1,2,3]triazole 35.
Several methods for the deprotection of benzyl-substituted
heteroarenes have been reported,[13] and on this basis, the
deprotection of 4-phenyl-2-benzyl-1,2,3-triazole 7 was per-
formed (Scheme 8). The reaction of 7 with tBuOK and O2
bromide. Conversely, the use of an excess (3 equiv.) of the
electron-poor aryl bromides, 4-(trifluoromethyl)bromobenzene
or 3,5-bis(trifluoromethyl)bromobenzene in the presence of
2 mol% Pd(OAc)2 catalyst and 3 equiv. of KOAc afforded the
desired 4,5-diarylated triazoles 30 and 31 in 43% and 52%
yield, respectively.
Palladium-catalyzed intermolecular arylation associated with
an intramolecular CÀ H bond arylation represents a straightfor-
ward method for the step-economic synthesis of π-extended
(hetero)polyaromatic structures.[12a] Therefore, we applied the
Pd-catalyzed triazoles 4,5-diarylation methodology to the syn-
thesis of phenanthro[9,10-d][1,2,3]triazoles (Scheme 6 and
Scheme 7). From 2-benzyl-4-(4-(trifluoromethyl)phenyl)-1,2,3-
triazole 4 and 1,2-dibromobenzene in the presence of PdCl-
(C3H5)(dppb) catalyst, the targeted 2-benzyl-6-(trifluoromethyl)-
phenanthro[9,10-d][1,2,3]triazole 32 was obtained in 54% yield
(Scheme 6). A lower yield in the π-extended triazole 33 was
obtained using 16 as the triazole source.
°
It should be mentioned that the one pot synthesis of 2-
benzylphenanthro[9,10-d][1,2,3]triazole from 2,2’-dibromobi-
phenyl (1 equiv.) and 2-benzyl-1,2,3-triazole (1 equiv.) was also
bubbling during 2 hours at 60 C afforded the desired 4-phenyl-
1,2,3-triazole 36 in 93% yield.
Conclusion
In summary, we demonstrated that the direct arylation of
triazoles is not limited to 1-substituted 1,2,3-triazoles. Using
only 2 mol% of easily available Pd(OAc)2 catalyst precursor and
KOAc as inexpensive bases, 2-benzyl-1,2,3-triazole can be
arylated at C4-position affording a wide variety of 4-(hetero)
arylated 2-benzyl-1,2,3-triazoles in good yields. The access to
symmetrical and non-symmetrical 4,5-diaryl-2-benzyl-1,2,3-tria-
zoles in moderate yields via two CÀ H bond functionalizations is
also described. Finally, this new CÀ H arylation method was
applied to the easy synthesis of π-extended phenanthro[9,10-
d][1,2,3]triazoles by using two Pd-catalyzed intermolecular
arylations associated to an intramolecular CÀ H bond arylation.
Experimental Section
Scheme 6. Synthesis of 2-benzyl-phenanthro[9,10-d][1,2,3]triazoles.
General procedure for palladium-catalyzed direct
C4-arylations of 2-benzyl-1,2,3-triazole: products 1a, 2–23
The reaction of the aryl bromide (1 mmol), 2-benzyl-1,2,3-triazole
(0.318 g, 2 mmol), KOAc (0.196 g, 2 mmol) in the presence of
°
Pd(OAc)2 (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 C during 16 h,
under argon affords the coupling products 1a, 2–23 after
Scheme 7. Synthesis of 2-benzyl-phenanthro[9,10-d][1,2,3]triazoles.
Scheme 8. Deprotection of 4-phenyl-2-benzyl-1,2,3-triazole.
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evaporation of the solvent and purification on silica gel. Eluent
7.32 (m, 5H), 7.11 (t, J=8.4 Hz, 2H), 5.62 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 163.0 (d, J=247.8 Hz), 147.3, 135.4, 131.3, 128.9, 128.5,
128.1, 127.8 (d, J=8.3 Hz), 126.7 (d, J=3.3 Hz), 116.0 (d, J=21.8 Hz),
58.9. HRMS calcd for [M+Na]+ C15H12FN3Na 276.0908, found
276.0908.
heptane:diethyl ether 7:3 for compounds 1a, 1b, 2, 13; heptane:
diethyl ether 4:1 for compounds 3, 4, 7, 9–12, 14, 19; heptane:
diethyl ether 9:1 for compounds 5, 6, 8, 17, 18; heptane:diethyl
ether 19:1 for compounds 15 and 16; heptane:diethyl ether 3:7 for
compounds 20 and 22; heptane:diethyl ether 1:9 for compound
21; heptane:diethyl ether 2:3 for compound 23.
2-Benzyl-4-phenyl-1,2,3-triazole (7):[14] From bromobenzene
(0.157 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol) and
4-(2-Benzyl-1,2,3-triazol-4-yl)benzonitrile (1a): From 4-bromoben-
zonitrile (0.182 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol)
KOAc (0.196 g, 2 mmol), product 7 was obtained in 80% yield
1
°
(0.188 g) as a white solid: mp 78–80 C. H NMR (400 MHz, CDCl3): δ
and KOAc (0.196 g, 2 mmol), product 1a was obtained in 66% yield
7.87 (s, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.43 (t, J=7.8 Hz, 2H), 7.39–7.32
(m, 6H), 5.63 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 148.2, 135.5,
131.6, 130.5, 129.0, 128.9, 128.6, 128.4, 128.1, 126.1, 58.9. HRMS
calcd for [M+Na]+ C15H13N3Na 258.1002, found 258.1000.
1
°
(0.172 g) as a white solid: mp 101–103 C. H NMR (400 MHz, CDCl3):
δ 7.92 (s, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.70 (d, J=8.4 Hz, 2H), 7.37–
7.32 (m, 5H), 5.64 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 146.4, 135.0,
134.9, 132.8, 132.1, 129.0, 128.6, 128.2, 126.5, 118.8, 112.0, 59.2.
HRMS calcd for [M+Na]+ C16H12N4Na 283.0954, found 283.0954.
2-Benzyl-4-(4-(tert-butyl)phenyl)-1,2,3-triazole (8): From 1-bromo-
4-tert-butylbenzene (0.213 g, 1 mmol), 2-benzyl-1,2,3-triazole
(0.318 g, 2 mmol) and KOAc (0.196 g, 2 mmol), product 8 was
obtained in 71% yield (0.207 g) as a colorless oil. 1H NMR (400 MHz,
CDCl3): δ 7.89 (s, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H),
7.39–7.32 (m, 5H), 5.66 (s, 2H), 1.39 (s, 9H). 13C NMR (100 MHz,
CDCl3): δ 151.6, 148.1, 135.6, 131.4, 128.8, 128.3, 128.0, 127.7, 125.8,
125.7, 58.7, 34.7, 31.4. HRMS calcd for [M+Na]+ C19H21N3Na
314.1628, found 314.1630.
4,4’-(2-Benzyl-1,2,3-triazole-4,5-diyl)dibenzonitrile (1b) was also
isolated in low yield as a white solid: mp 111–113 C: 1H NMR
°
(400 MHz, CDCl3): δ 7.67 (d, J=8.4 Hz, 4H), 7.62 (d, J=8.4 Hz, 4H),
7.47–7.32 (m, 5H), 5.65 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 143.7,
135.1, 134.5, 132.7, 129.1 128.9, 128.8, 128.5, 118.5, 112.6, 59.4.
HRMS calcd for [M+Na]+ C23H15N5Na 384.1220, found 384.1224.
4-(2-Benzyl-1,2,3-triazol-4-yl)benzaldehyde (2): From 4-bromoben-
zaldehyde (0.185 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.196 g, 2 mmol), product 2 was obtained in
2-Benzyl-4-(4-methoxyphenyl)-1,2,3-triazole (9): From 4-bromoa-
nisole (0.187 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol)
52% yield (0.137 g) as a white solid: mp 88–90 C. 1H NMR
and KOAc (0.196 g, 2 mmol), product 9 was obtained in 65% yield
°
1
°
(400 MHz, CDCl3): δ 10.03 (s, 1H), 7.99-7.90 (m, 5H), 7.40–7.32 (m,
5H), 5.65 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 191.8, 146.9, 136.3,
136.2, 135.1, 132.3, 130.5, 129.0, 128.6, 128.2, 126.5, 59.2. HRMS
calcd for [M+Na]+ C16H13N3ONa 318.1213, found 318.1210.
(0.172 g) as a white solid: mp 79–81 C. H NMR (400 MHz, CDCl3): δ
7.80 (s, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.37-7.32 (m, 5H), 6.96 (d, J=
8.4 Hz, 2H), 5.62 (s, 2H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
159.9, 148.0, 135.6, 131.0, 128.8, 128.3, 128.0, 127.3, 123.2, 114.4,
58.7, 55.4. HRMS calcd for [M+Na]+ C16H15N3ONa 288.1107, found
288.1110.
Ethyl 4-(2-benzyl-1,2,3-triazol-4-yl)benzoate (3): From ethyl 4-
bromobenzoate (0.229 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.196 g, 2 mmol), product 3 was obtained in
3-(2-Benzyl-1,2,3-triazol-4-yl)benzonitrile (10): From 3-bromoben-
zonitrile (0.182 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol)
56% yield (0.172 g) as a white solid: mp 82–84 C. 1H NMR
°
(400 MHz, CDCl3): δ 8.09 (d, J=8.4 Hz, 2H), 7.92 (s, 1H), 7.85 (d, J=
8.4 Hz, 2H), 7.39–7.32 (m, 5H), 5.64 (s, 2H), 4.39 (q, J=7.6 Hz, 2H),
1.41 (t, J=7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 166.4, 147.2,
135.2, 134.7, 132.1, 130.4, 130.3, 129.0, 128.6, 128.2, 125.8, 61.2,
59.1, 14.5. HRMS calcd for [M+Na]+ C18H17N3O2Na 330.1213, found
330.1214.
and KOAc (0.196 g, 2 mmol), product 10 was obtained in 67% yield
1
°
(0.174 g) as a white solid: mp 80–82 C. H NMR (400 MHz, CDCl3): δ
8.08 (s, 1H), 7.99 (d, J=8.4 Hz, 1H), 7.89 (s, 1H), 7.61 (d, J=8.4 Hz,
1H), 7.54 (t, J=7.8 Hz, 1H), 7.37–7.32 (m, 5H), 5.63 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ 146.1, 135.0, 131.8, 131.7, 131.6, 130.1, 129.8,
129.5, 129.0, 128.6, 128.2, 118.6, 113.3, 59.1. HRMS calcd for [M+
Na]+ C16H12N4Na 283.0954, found 283.0956.
2-Benzyl-4-(4-(trifluoromethyl)phenyl)-1,2,3-triazole (4): From 4-
bromobenzotrifluoride (0.225 g, 1 mmol), 2-benzyl-1,2,3-triazole
3-(2-Benzyl-1,2,3-triazol-4-yl)benzaldehyde (11): From 3-bromo-
benzaldehyde (0.185 g, 1 mmol), (0.182 g, 1 mmol), 2-benzyl-1,2,3-
triazole (0.318 g, 2 mmol) and KOAc (0.196 g, 2 mmol), product 11
(0.318 g, 2 mmol) and KOAc (0.196 g, 2 mmol), product 4 was
1
°
obtained in 54% yield (0.164 g) as a yellow solid: mp 55–57 C. H
°
NMR (400 MHz, CDCl3): δ 7.92 (s, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.68 (d,
J=8.4 Hz, 2H), 7.39–7.32 (m, 5H), 5.65 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 146.8, 135.1, 133.9, 131.9, 130.3 (q, J=32.5 Hz), 128.9,
128.6, 128.2, 126.2, 125.9 (q, J=3.8 Hz), 124.1 (q, J=272.0 Hz), 59.0.
HRMS calcd for [M+Na]+ C16H12F3N3Na 326.0875, found 326.0873.
was obtained in 50% yield (0.132 g) as a white solid: mp 85–87 C.
1H NMR (400 MHz, CDCl3): δ 10.07 (s, 1H), 8.29 (s, 1H), 8.05 (d, J=
8.4 Hz, 1H), 7.94 (s, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.59 (t, J=7.8 Hz,
1H), 7.39–7.32 (m, 5H), 5.64 (s, 2H). 13C NMR (100 MHz, CDCl3): δ
192.1, 146.9, 137.0, 135.2, 131.8, 131.7, 131.6, 129.7, 129.6, 129.0,
128.5, 128.2, 127.1, 59.0. HRMS calcd for [M+Na]+ C16H13N3ONa
286.0951, found 286.0953.
2-Benzyl-4-(4-chlorophenyl)-1,2,3-triazole (5): From 4-bromochlor-
obenzene (0.191 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.196 g, 2 mmol), product 5 was obtained in
Methyl 3-(2-benzyl-1,2,3-triazol-4-yl)benzoate (12): From methyl
79% yield (0.212 g) as a white solid: mp 60–62 C. 1H NMR
3-bromobenzoate
(0.215 g,
1 mmol),
2-benzyl-1,2,3-triazole
°
(400 MHz, CDCl3): δ 7.84 (s, 1H), 7.71 (d, J=8.4 Hz, 2H), 7.39 (d, J=
8.4 Hz, 2H), 7.37–7.32 (m, 5H), 5.62 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 147.2, 135.3, 134.5, 134.3, 131.5, 129.2, 128.9, 128.5, 128.1,
127.3, 59.0. HRMS calcd for [M+Na]+ C15H12ClN3Na 292.0612, found
292.0615.
(0.318 g, 2 mmol) and KOAc (0.196 g, 2 mmol), product 12 was
obtained in 86% yield (0.252 g) as a colorless oil. 1H NMR (400 MHz,
CDCl3): δ 8.44 (s, 1H), 8.01 (d, J=8.4 Hz, 1H), 8.00 (d, J=8.4 Hz, 1H),
7.93 (s, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.39-7.32 (m, 5H), 5.64 (s, 2H),
3.95 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 166.9, 147.3, 135.3, 131.7,
131.0, 130.9, 130.4, 129.6, 129.1, 129.0, 128.5, 128.2, 127.1, 59.0,
52.4. HRMS calcd for [M+Na]+ C17H15N3O2Na 316.1057, found
316.1059.
2-Benzyl-4-(4-fluorophenyl)-1,2,3-triazole (6): From 4-bromofluor-
obenzene (0.175 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.196 g, 2 mmol), product 6 was obtained in
74% yield (0.187 g) as a white solid: mp 53–55 C. 1H NMR
2-(2-Benzyl-1,2,3-triazol-4-yl)benzonitrile (13): From 2-bromoben-
zonitrile (0.182 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol)
°
(400 MHz, CDCl3): δ 7.82 (s, 1H), 7.76 (dd, J=8.4, 5.3 Hz, 2H), 7.39–
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and KOAc (0.196 g, 2 mmol), product 13 was obtained in 79% yield
3-(2-Benzyl-1,2,3-triazol-4-yl)pyridine (20): From 3-bromopyridine
(0.158 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol) and
1
°
(0.205 g) as a white solid: mp 58–60 C. H NMR (400 MHz, CDCl3): δ
8.27 (s, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.65 (t,
J=7.9 Hz, 1H), 7.46-7.32 (m, 6H), 5.66 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 144.7, 134.9, 134.1, 133.6, 133.4, 133.1, 128.9, 128.7, 128.6,
128.5, 128.3, 118.8, 109.7, 59.1. HRMS calcd for [M+K]+ C16H12N4K
299.0693, found 299.0687.
KOAc (0.196 g, 2 mmol), product 20 was obtained in 54% yield
1
°
(0.127 g) as a white solid: mp 74–76 C. H NMR (400 MHz, CDCl3): δ
9.04 (bs, 1H), 8.60 (bs, 1H), 8.09 (d, J=8.2 Hz, 1H), 7.91 (s, 1H), 7.38–
7.32 (m, 6H), 5.64 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 149.3, 147.2,
145.2, 135.1, 133.5, 131.7, 129.0, 128.6, 128.2, 126.8, 123.9, 59.0.
HRMS calcd for [M+Na]+ C14H12N4Na 259.0954, found 259.0958.
2-Benzyl-4-(2-(trifluoromethyl)phenyl)-1,2,3-triazole (14): From 2-
bromobenzotrifluoride (0.225 g, 1 mmol), 2-benzyl-1,2,3-triazole
(0.318 g, 2 mmol) and KOAc (0.196 g, 2 mmol), product 14 was
obtained in 83% yield (0.251 g) as a colorless oil. 1H NMR (400 MHz,
CDCl3): δ 7.82 (s, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.70 (d, J=8.4 Hz, 1H),
7.59 (t, J=7.9 Hz, 1H), 7.49 (t, J=7.9 Hz, 1H), 7.39–7.32 (m, 5H), 5.67
(s, 2H). 13C NMR (100 MHz, CDCl3): δ 145.5, 135.3, 134.3 (q, J=
4.2 Hz), 132.0, 131.9, 131.8, 129.6 (q, J=1.8 Hz), 128.9, 128.5 (q, J=
32.5 Hz), 128.0, 126.4 (q, J=5.6 Hz), 124.0 (q, J=273.5 Hz), 58.8.
HRMS calcd for [M+Na]+ C16H12F3N3Na 326.0876, found 326.0877.
4-(2-Benzyl-1,2,3-triazol-4-yl)pyridine (21): From 4-bromopyridine
hydrochloride (0.194 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.294 g, 3 mmol), product 21 was obtained in
51% yield (0.120 g) as a white solid: mp 79–81 C. 1H NMR
°
(400 MHz, CDCl3): δ 8.68 (bs, 2H), 7.96 (s, 1H), 7.68 (d, J=4.8 Hz, 2H),
7.36—7.29 (m, 5H), 5.64 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 150.6,
145.7, 137.9, 134.9, 132.4, 129.0, 128.7, 128.2, 120.4, 59.2. HRMS
calcd for [M+Na]+ C14H12N4Na 259.0954, found 259.0952.
3-(2-Benzyl-1,2,3-triazol-4-yl)quinoline (22): From 3-bromoquino-
2-Benzyl-4-(2-chlorophenyl)-1,2,3-triazole (15): From 2-bromo-
chlorobenzene (0.191 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.196 g, 2 mmol), product 15 was obtained in
line (0.208 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol) and
KOAc (0.196 g, 2 mmol), product 22 was obtained in 56% yield
1
°
(0.160 g) as a white solid: mp 65–67 C. H NMR (400 MHz, CDCl3): δ
78% yield (0.210 g) as a white solid: mp 50–52 C. 1H NMR
9.35 (bs, 1H), 8.51 (s, 1H), 8.13 (d, J=8.4 Hz, 1H), 8.04 (s, 1H), 7.87 (d,
J=8.2 Hz, 1H), 7.72 (t, J=7.8 Hz, 1H), 7.57 (t, J=7.8 Hz, 1H), 7.42–
7.26 (m, 5H), 5.69 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 148.6, 148.1,
145.5, 135.1, 132.3, 131.9, 129.9, 129.6, 129.0, 128.6, 128.2, 128.1,
127.3, 59.1. HRMS calcd for [M+Na]+ C18H14N4Na 309.1111, found
309.1112.
°
(400 MHz, CDCl3): δ 8.16 (s, 1H), 7.90 (dd, J=7.8, 2.0 Hz, 1H), 7.47
(dd, J=7.8, 1.6 Hz, 1H), 7.40-7.32 (m, 7H), 5.66 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ 145.3, 135.3, 134.7, 132.2, 130.5, 129.5, 129.4,
128.9, 128.5, 128.1, 127.1, 58.9. HRMS calcd for [M+Na]+
C15H12ClN3Na 292.0612, found 292.0613.
2-Benzyl-4-(3,5-bis(trifluoromethyl)phenyl)-1,2,3-triazole
From 3,5-bis(trifluoromethyl)bromobenzene (0.293 g, 1 mmol), 2-
benzyl-1,2,3-triazole (0.318 g, 2 mmol) and KOAc (0.196 g, 2 mmol),
(16):
4-(2-Benzyl-1,2,3-triazol-4-yl)isoquinoline (23): From 4-bromoiso-
quinoline (0.208 g, (0.182 g, 1 mmol), 2-benzyl-1,2,3-triazole
(0.318 g, 2 mmol) and KOAc (0.196 g, 2 mmol), product 23 was
1
°
product 16 was obtained in 44% yield (0.163 g) as a white solid:
obtained in 78% yield (0.223 g) as a white solid: mp 127–129 C. H
1
°
mp 111–113 C. H NMR (400 MHz, CDCl3): δ 8.22 (s, 2H), 7.97 (s, 1H),
NMR (400 MHz, CDCl3): δ 9.26 (bs, 1H), 8.76 (bs, 1H), 8.49 (d, J=
8.4 Hz, 1H), 8.01 (d, J=8.2 Hz, 1H), 7.97 (s, 1H), 7.75 (t, J=7.8 Hz,
1H), 7.64 (t, J=7.8 Hz, 1H), 7.45–7.30 (m, 5H), 5.73 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ 153.2, 144.8, 143.1, 135.2, 134.2, 133.4, 131.2,
128.9, 128.5, 128.2, 128.1, 127.5, 124.8, 121.7, 59.1. HRMS calcd for
[M+Na]+ C18H14N4Na 309.1111, found 309.1111.
7.84 (s, 1H), 7.40–7.32 (m, 5H), 5.65 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 145.6, 134.9, 132.8, 132.4 (q, J=32.5 Hz), 131.9, 129.0,
128.7, 128.2, 125.9, 123.5 (q, J=272.5 Hz), 121.9 (q, J=3.8 Hz), 59.2.
HRMS calcd for [M+Na]+ C17H11F6N3Na 394.0749, found 394.0750.
2-Benzyl-4-(naphthalen-2-yl)-1,2,3-triazole (17): From 2-bromo-
naphthalene (0.207 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.196 g, 2 mmol), product 17 was obtained in
General procedure for palladium-catalyzed direct
C5-arylations of 2-benzyl-4-aryl-1,2,3-triazole: products 24–29
55% yield (0.157 g) as a white solid: mp 91–93 C. 1H NMR
°
(400 MHz, CDCl3): δ 8.26 (s, 1H), 8.00 (s, 1H), 7.95–7.82 (m, 4H), 7.55–
7.45 (m, 2H), 7.42–7.32 (m, 5H), 5.68 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 148.2, 135.4, 133.6, 133.4, 131.8, 128.9, 128.7, 128.4, 128.3,
128.1, 127.9, 127.8, 126.6, 126.4, 124.9, 124.1, 58.9. HRMS calcd for
[M+Na]+ C19H15N3Na 308.1158, found 308.1159.
The reaction of the aryl bromide (2 mmol), 2-benzyl-4-aryl-1,2,3-
triazole (1 mmol), KOAc (0.196 g, 2 mmol) in the presence of
°
Pd(OAc)2 (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 C during 16 h,
under argon affords the coupling products 24–29 after evaporation
of the solvent and purification on silica gel. Eluent heptane:diethyl
ether 4:1 for compounds 24 and 28; heptane:diethyl ether 9:1 for
compound 25; heptane:diethyl ether 19:1 for compounds 26 and
29; heptane:diethyl ether 7:3 for compound 27.
2-Benzyl-4-(naphthalen-1-yl)-1,2,3-triazole (18): From 1-bromo-
naphthalene (0.207 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g,
2 mmol) and KOAc (0.196 g, 2 mmol), product 18 was obtained in
1
74% yield (0.211 g) as a colorless oil. H NMR (400 MHz, CDCl3): δ
4-(2-Benzyl-5-phenyl-1,2,3-triazol-4-yl)benzonitrile (24): From 4-
bromobenzonitrile (0.364 g, 2 mmol), 2-benzyl-4-phenyl-1,2,3-
triazole 7 (0.235 g, 1 mmol) and KOAc (0.196 g, 2 mmol), product
8.42 (m, 1H), 7.92 (s, 1H), 7.91–7.57 (m, 2H), 7.69 (d, J=7.8 Hz, 1H),
7.58–7.49 (m, 3H), 7.45–7.32 (m, 5H), 5.73 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 147.5, 135.5, 134.5, 134.1, 129.2, 129.0, 128.6, 128.5, 128.2,
128.0, 127.4, 126.9, 126.2, 125.6, 125.4, 59.0. HRMS calcd for [M+
Na]+ C19H15N3Na 308.1158, found 308.1158.
24 was obtained in 68% yield (0.228 g) as a white solid: mp 97–
1
°
99 C. H NMR (400 MHz, CDCl3): δ 7.68 (d, J=8.5 Hz, 2H), 7.62 (d,
J=8.5 Hz, 2H), 7.52–7.32 (m, 10H), 5.65 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 145.7, 143.0, 135.8, 135.0, 132.4, 130.5, 129.1, 129.0, 128.9,
128.7, 128.6, 128.4, 118.8, 111.9, 59.2. HRMS calcd for [M+Na]+
C22H16N4Na 359.1267, found 359.1270.
4-(Anthracen-9-yl)-2-benzyl-1,2,3-triazole (19): From 9-bromoan-
thracene (0.257 g, 1 mmol), 2-benzyl-1,2,3-triazole (0.318 g, 2 mmol)
and KOAc (0.196 g, 2 mmol), product 19 was obtained in 57% yield
(0.191 g) as a yellow solid: mp 100–102 C. 1H NMR (400 MHz,
°
2-Benzyl-4-(4-chlorophenyl)-5-phenyl-1,2,3-triazole (25):[15] From
4-bromochlorobenzene (0.382 g, 2 mmol), 2-benzyl-4-phenyl-1,2,3-
triazole 7 (0.235 g, 1 mmol) and KOAc (0.196 g, 2 mmol), product
CDCl3): δ 8.56 (s, 1H), 8.06 (d, J=8.2 Hz, 2H), 7.92 (s, 1H), 7.85 (d, J=
8.2 Hz, 2H), 7.55–7.36 (m, 9H), 5.85 (s, 2H). 13C NMR (100 MHz,
CDCl3): δ 144.8, 136.8, 135.5, 131.3, 131.2, 129.0, 128.6, 128.5, 128.4,
128.2, 126.3, 125.9, 125.3, 124.6, 59.0. HRMS calcd for [M+Na]+
C23H17N3Na 358.1315, found 358.1320.
1
25 was obtained in 51% yield (0.176 g) as a colorless oil. H NMR
(400 MHz, CDCl3): δ 7.55–7.47 (m, 4H), 7.44 (d, J=8.5 Hz, 2H), 7.40–
7.31 (m, 8H), 5.64 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 145.0, 143.8,
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135.3, 134.4, 130.9, 129.7, 129.0, 128.9, 128.8, 128.6, 128.5, 128.4,
272.0 Hz), 59.3. HRMS calcd for [M+Na]+ C23H15F6N3Na 470.1062,
found 470.1061.
128.3, 59.0. HRMS calcd for [M+Na]+ C21H16ClN3Na 368.0925, found
368.0928.
2-Benzyl-4,5-bis(3,5-bis(trifluoromethyl)phenyl)-1,2,3-triazole
(31): From 3,5-bis(trifluoromethyl)bromobenzene (0.879 g, 3 mmol),
2-benzyl-1,2,3-triazole (0.159 g, 1 mmol) and KOAc (0.294 g,
3 mmol), product 31 was obtained in 52% yield (0.303 g) as a
2-Benzyl-4-(4-(tert-butyl)phenyl)-5-(4-chlorophenyl)-1,2,3-triazole
(26): From 4-bromochlorobenzene (0.382 g, 2 mmol), 2-benzyl-4-(4-
(tert-butyl)phenyl)-1,2,3-triazole
8 (0.291 g, 1 mmol) and KOAc
1
(0.196 g, 2 mmol), product 26 was obtained in 42% yield (0.168 g)
colorless oil. H NMR (400 MHz, CDCl3): δ 8.03 (s, 4H), 7.93 (s, 2H),
1
7.48 (d, J=8.4 Hz, 2H), 7.45-7.32 (m, 3H), 5.71 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ 142.6, 134.4, 132.6 (q, J=32.5 Hz), 129.2, 129.0,
128.5, 128.2, 123.1 (q, J=272.5 Hz), 122.7 (q, J=3.8 Hz), 59.6. HRMS
calcd for [M+Na]+ C25H13F12N3Na 606.0810, found 606.0817.
°
as a white solid: mp 113–115 C. H NMR (400 MHz, CDCl3): δ 7.52
(d, J=8.4 Hz, 2H), 7.48–7.31 (m, 11H), 5.63 (s, 2H), 1.33 (s, 9H). 13C
NMR (100 MHz, CDCl3): δ 151.7, 145.0, 143.7, 135.4, 134.3, 129.9,
129.7, 128.9, 128.8, 128.5, 128.3, 128.0, 127.9, 125.7, 58.9, 34.8, 31.4.
HRMS calcd for [M+Na]+ C25H24ClN3Na 424.1551, found 424.1552.
4-(2-Benzyl-5-(4-methoxyphenyl)-1,2,3-triazol-4-yl)benzonitrile
(27): From 4-bromobenzonitrile (0.364 g, 2 mmol), 2-benzyl-4-(4-
General procedure for palladium-catalyzed direct
C5-arylations followed by intramolecular reaction of
2-benzyl-4-aryl-1,2,3-triazoles: products 32–35
methoxyphenyl)-1,2,3-triazole
9 (0.265 g, 1 mmol) and KOAc
(0.196 g, 2 mmol), product 27 was obtained in 40% yield (0.146 g)
1
°
as a white solid: mp 70–72 C. H NMR (400 MHz, CDCl3): δ 7.69 (d,
The reaction of the aryl dihalide (2 mmol), 2-benzyl-4-aryl-1,2,3-
triazole (1 mmol), KOPiv (0.280 g, 2 mmol) in the presence of PdCl
(C3H5)(dppb) (0.122 g, 0.2 mmol) in DMA (4 mL) at 150 C during
16 h, under argon affords the coupling products 32–35 after
evaporation of the solvent and purification on silica gel. Eluent
heptane:diethyl ether 9:1 for compound 32; heptane:diethyl ether
19:1 for compounds 33–35.
J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 7.46–7.32 (m, 7H), 6.92 (d, J=
8.4 Hz, 2H), 5.63 (s, 2H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
160.2, 145.6, 142.6, 136.0, 135.1, 132.4, 129.9, 129.0, 128.6, 128.5,
128.4, 122.8, 118.9, 114.4, 111.8, 59.1, 55.5. HRMS calcd for [M+
Na]+ C23H18N4ONa 389.1373, found 389.1377.
°
2-Benzyl-4-(4-methoxyphenyl)-5-(4-(trifluoromethyl)phenyl)-
1,2,3-triazole (28): From 4-bromobenzotrifluoride (0.450 g,
2-Benzyl-6-(trifluoromethyl)-phenanthro[9,10-d][1,2,3]triazole
(32): From 1,2-dibromobenzene (0.472 g, 2 mmol), 2-benzyl-4-(4-
(trifluoromethyl)phenyl)-1,2,3-triazole 4 (0.303 g, 1 mmol) and KO-
Piv (0.280 g, 2 mmol), product 32 was obtained in 54% yield
2 mmol), 2-benzyl-4-(4-methoxyphenyl)-1,2,3-triazole
9 (0.265 g,
1 mmol) and KOAc (0.196 g, 2 mmol), product 28 was obtained in
53% yield (0.217 g) as a white solid: mp 97–99 C. 1H NMR
°
(0.203 g) as a yellow solid: mp 118–120 C. 1H NMR (400 MHz,
°
(400 MHz, CDCl3): δ 7.70 (d, J=8.4 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H),
7.45 (d, J=8.3 Hz, 4H), 7.41-7.32 (m, 3H), 6.92 (d, J=8.4 Hz, 2H),
5.64 (s, 2H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.1, 145.3,
143.1, 135.2, 135.0, 130.1 (q, J=32.5 Hz), 129.8, 128.9, 128.5, 128.4,
128.3, 125.6 (q, J=3.8 Hz), 124.2 (q, J=272.0 Hz), 123.1, 114.3, 59.0,
55.4. HRMS calcd for [M+Na]+ C23H18F3N3ONa 432.1294, found
432.1293.
CDCl3): δ 8.76 (s, 1H), 8.56 (d, J=8.3 Hz, 1H), 8.53–8.46 (m, 2H), 7.82
(d, J=8.3 Hz, 1H), 7.68-7.63 (m, 2H), 7.47 (d, J=8.4 Hz, 2H), 7.42-
7.33 (m, 3H), 5.91 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 142.1, 140.6,
135.2, 130.3, 129.7, 129.5 (q, J=32.5 Hz), 129.0, 128.7, 128.5, 128.3,
128.1, 127.1, 125.0, 124.6 (q, J=272.0 Hz), 124.5, 123.9, 123.8 (m),
121.0 (q, J=4.0 Hz), 60.0. HRMS calcd for [M+Na]+ C22H14F3N3Na
400.1032, found 400.1031.
2-Benzyl-4-(3,5-bis(trifluoromethyl)phenyl)-5-phenyl-1,2,3-
triazole (29) From 3,5-bis(trifluoromethyl)bromobenzene (0.586 g,
2 mmol), 2-benzyl-4-phenyl-1,2,3-triazole 7 (0.235 g, 1 mmol) and
KOAc (0.196 g, 2 mmol), product 29 was obtained in 60% yield
2-Benzyl-5,7-bis(trifluoromethyl)-phenanthro[9,10-d][1,2,3]
triazole (33): From 1,2-dibromobenzene (0.472 g, 2 mmol), 2-
benzyl-4-(3,5-bis(trifluoromethyl)phenyl)-1,2,3-triazole 16 (0.371 g,
1 mmol) and KOPiv (0.280 g, 2 mmol), product 33 was obtained in
1
(0.268 g) as a colorless oil. H NMR (400 MHz, CDCl3): δ 8.06 (s, 2H),
42% yield (0.187 g) as a white solid: mp 147–149 C. 1H NMR
°
7.85 (s, 1H), 7.55–7.50 (m, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.45–7.36 (m,
6H), 5.69 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 145.8, 142.0, 134.9,
133.4, 132.1 (q, J=32.5 Hz), 130.1, 129.3, 129.1, 129.0, 128.7, 128.5,
128.4, 128.1, 123.1 (q, J=272.5 Hz), 121.8 (q, J=3.8 Hz), 59.2. HRMS
calcd for [M+Na]+ C23H15F6N3Na 470.1062, found 470.1061.
(400 MHz, CDCl3): δ 9.01 (s, 1H), 8.63 (d, J=8.3 Hz, 1H), 8.56 (d, J=
8.0 Hz, 1H), 8.27 (s, 1H), 7.75 (t, J=7.9 Hz, 1H), 7.64 (t, J=7.9 Hz,
1H), 7.46 (d, J=8.4 Hz, 2H), 7.43–7.32 (m, 3H), 5.91 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ 141.8, 140.6, 135.0, 132.2, 130.0 (q, J=32.5 Hz),
129.7, 129.1, 128.8, 128.3, 127.9, 127.3, 126.4, 124.8 (q, J=272.5 Hz),
124.5 (m), 123.6, 123.5 (q, J=272.5 Hz), 60.2. HRMS calcd for [M+
Na]+ C23H13F6N3Na 468.0906, found 468.0904.
General procedure for palladium-catalyzed direct
C4,C5-diarylations of 2-benzyl-1,2,3-triazole: products 30and
31
2-Benzyl-6-chloro-9-(trifluoromethyl)-phenanthro[9,10-d][1,2,3]
triazole (34): From 2-bromo-4-chloro-1-iodobenzene (0.634 g,
The reaction of the aryl bromide (3 mmol), 2-benzyl-1,2,3-triazole
(0.159 g, 1 mmol), KOAc (0.294 g, 3 mmol) in the presence of
2 mmol), 2-benzyl-4-(4-(trifluoromethyl)phenyl)-1,2,3-triazole
(0.303 g, 1 mmol) and KOPiv (0.280 g, 2 mmol), product 34 was
4
1
°
°
Pd(OAc)2 (2.4 mg, 0.02 mmol) in DMA (4 mL) at 150 C during 16 h,
obtained in 45% yield (0.185 g) as a white solid: mp 179–181 C. H
under argon affords the coupling products 30 and 31 after
evaporation of the solvent and purification on silica gel. Eluent
heptane:diethyl ether 19:1.
NMR (400 MHz, CDCl3): δ 8.69 (s, 1H), 8.59 (d, J=8.3 Hz, 1H), 8.49 (d,
J=2.0 Hz, 1H), 8.43 (d, J=8.3 Hz, 1H), 7.87 (d, J=8.3 Hz, 1H), 7.63
(dd, J=8.3, 2.0 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.42-7.33 (m, 3H),
5.91 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 141.6, 140.5, 135.0, 134.4,
131.1, 129.7 (q, J=32.5 Hz), 129.3, 129.0, 128.9, 128.8, 128.3, 127.5,
125.4, 124.7, 124.5 (q, J=3.7 Hz), 124.4 (q, J=272.0 Hz), 123.8,
123.4, 121.1 (q, J=3.7 Hz), 60.1. HRMS calcd for [M+Na]+
C22H13ClF3N3Na 434.0642, found 434.0646.
2-Benzyl-4,5-bis(4-(trifluoromethyl)phenyl)-1,2,3-triazole
(30):
From 4-bromobenzotrifluoride (0.675 g, 3 mmol), 2-benzyl-1,2,3-
triazole (0.159 g, 1 mmol) and KOAc (0.196 g, 2 mmol), product 30
°
was obtained in 43% yield (0.192 g) as a white solid: mp 61–63 C.
1H NMR (400 MHz, CDCl3): δ 7.67 (d, J=8.4 Hz, 4H), 7.64 (d, J=
8.4 Hz, 4H), 7.47 (d, J=8.4 Hz, 2H), 7.42–7.33 (m, 3H), 5.67 (s, 2H).
13C NMR (100 MHz, CDCl3): δ 144.0, 134.9, 134.4, 130.7 (q, J=
32.5 Hz), 129.0, 128.8, 128.7, 128.4, 125.8 (q, J=3.8 Hz), 124.1 (q, J=
2-Benzyl-6,9-bis(trifluoromethyl)-phenanthro[9,10-d][1,2,3]
triazole (35): From 2-bromo-1-iodo-4-(trifluoromethyl)benzene
(0.351 g, 2 mmol), 2-benzyl-4-(4-(trifluoromethyl)phenyl)-1,2,3-
Eur. J. Org. Chem. 2021, 2375–2382
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© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202100324
Fuse, T. Morita, K. Johmoto, H. Uekusa, H. Tanaka, Chem. Eur. J. 2015, 21,
triazole 4 (0.303 g, 1 mmol) and KOPiv (0.280 g, 2 mmol), product
14370–14375; h) W. F. Vernier, L. Gomez, Tetrahedron Lett. 2017, 58,
4587–4590; i) J. H. Jang, S. Ahn, S. E. Park, S. Kim, H. R. Byon, J. M. Joo,
Org. Lett. 2020, 22, 1280–1285.
35 was obtained in 36% yield (0.160 g) as a white solid: mp 192–
1
°
194 C. H NMR (400 MHz, CDCl3): δ 8.82 (s, 2H), 8.66 (d, J=8.3 Hz,
2H), 7.94 (d, J=8.3 Hz, 2H), 7.51 (d, J=8.4 Hz, 2H), 7.42–7.33 (m,
3H), 5.96 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 141.2, 134.9, 130.1 (q,
J=32.5 Hz), 129.6, 129.1, 128.8, 128.4, 127.5, 124.8, 124.7 (q, J=
3.7 Hz), 124.2 (q, J=272.0 Hz), 121.1 (q, J=3.9 Hz), 60.3. HRMS calcd
for [M+Na]+ C23H13F6N3Na 468.0906, found 468.0902.
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A. S. Dudnik, V. Gevorgyan, Org. Lett. 2007, 9, 2333–2336; b) M. Iwasaki,
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4-Phenyl-1,2,3-triazole (36): 2-Benzyl-4-phenyl-1,2,3-triazole
7
(0.118 g, 0.5 mmol), tBuOK (0.280 g, 2.5 mmol) under O2 bubbling
°
were reacted in DMSO at 60 C during 2 h. The reaction was
quenched with saturated ammonium chloride. The product was
extracted three times with EtOAc. The organics were combined,
dried over Na2SO4 and concentrated. The crude mixture was
purified on silica gel to afford the product 36 in 93% (0.067 g) yield
°
as a white solid: mp 141–143 C. Eluent heptane:diethyl ether 7:3.
1H NMR (400 MHz, CDCl3): δ 12.27 (bs, 1H), 7.99 (s, 1H), 7.83 (d, J=
8.3 Hz, 2H), 7.49 (t, J=7.9 Hz, 2H), 7.38 (t, J=7.9 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 147.5, 130.0, 129.1, 128.9, 126.3. HRMS calcd for
[M+Na]+ C8H7N3Na 168.0532, found 168.0534.
Acknowledgements
We are grateful to the ANR for a grant to X. S. We thank CNRS
and “Rennes Metropole” for providing financial support.
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Conflict of Interest
The authors declare no conflict of interest.
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Manuscript received: March 17, 2021
Revised manuscript received: March 24, 2021
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