Synthesis of 2-Aryl-2 H-benzotrizoles from azobenzenes and N-sulfonyl azides through sequential rhodium-catalyzed amidation and oxidation in one pot

Article abstract of DOI:10.1021/ol501250t

An efficient synthetic method of 2-aryl-2H-benzotriazoles from nonprefunctionalized azobenzenes and N-sulfonyl azides via sequential Rh-catalyzed amidation (C-N bond formation) and oxidation (N-N bond formation) with PhI(OAc)₂ in one pot is reported.

Full text of DOI:10.1021/ol501250t

Letter
pubs.acs.org/OrgLett
Synthesis of 2‑Aryl‑2H‑benzotrizoles from Azobenzenes and
N‑Sulfonyl Azides through Sequential Rhodium-Catalyzed Amidation
and Oxidation in One Pot
Taekyu Ryu, Jiae Min, Wonseok Choi, Woo Hyung Jeon, and Phil Ho Lee*
Department of Chemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea
S
* Supporting Information
ABSTRACT: An efficient synthetic method of 2-aryl-2H-benzotriazoles from nonprefunctionalized azobenzenes and N-sulfonyl
azides via sequential Rh-catalyzed amidation (C−N bond formation) and oxidation (N−N bond formation) with PhI(OAc)2 in
one pot is reported.
evelopment of synthetic methods of 2-aryl-2H-benzo-
triazole derivatives from easily accessible reactants is
highly significant because it is an essential component of
pharmaceuticals, UV stabilizers, and organic electronic
materials (Figure 1).1 Because benzotriazoles exist as N1-,
benzotriazoles from azobenzenes and N-sulfonyl azides through
sequential Rh-catalyzed amidation (C−N bond formation) and
oxidation (N−N bond formation) in one pot (Scheme 1).12
D
Scheme 1. Synthesis of 2-Aryl-2H-benzotrizoles from
Azobenzenes and N-Sulfonyl Azides in One Pot
First, we examined the amidation of azobenzene 2a (0.2
mmol, 1.0 equiv) with tosyl azide 1a (1.2 equiv) in the presence
of [Cp*RhCl2]2 (4 mol %) with a multidude of additives (16
mol %) and solvents (Table 1 and see the Supporting
Information (SI)). DCE was the solvent of choice (entry 5);
other reaction media such as tert-amyl alcohol, 1,4-dioxane,
chlorobenzene, and THF were less effective (entries 1−4).
Among the additives such as AgSbF6, AgNTf2, AgBF4, AgPF6,
and AgOTf, AgNTf2 gave the amidated azobenzene 3a in 66%
yield (entry 6). However, formation of diamidated azobenzene
4a was unavoidable. To increase the selectivity, the
stoichiometry of azobenzene (1.0, 1.2, 1.5, and 2.0 equiv)
was screened (entries 10−13). Use of an increased amount of
azobenzene gave improved results. Eventually, the amidation of
azobenzene 1a (2.0 equiv) with tosyl azide 1a (1.0 equiv) in the
presence of [Cp*RhCl2]2 (4 mol %) with AgNTf2 (16 mol %)
gave the best result in DCE at 90 °C under aerobic conditions,
producing 3a in 85% yield (entry 13).
Figure 1. Important compounds containing 2-aryl-2H-benzotriazole
moiety.
N2-, and N3-substituted isomers, the selective preparation of
benzotriazole represents an important synthetic challenge.2
Although a variety of synthetic methods for N1-arylation of
benzotriazole have been reported,3 a selective N2-arylation of
benzotriazole is still needed. To date, thermal decomposition of
o-azidoazobenzenes,4 reduction of 2-[(2-nitrophenyl)azo]-
phenols with thiourea S,S-dioxide,5 SmI2,6 or Zn7 and Cu-
catalyzed oxidative cyclization of azoanilines8 were reported for
N2-arylation of benzotriazoles. However, these methods
required prefunctionalized azobenzenes having an azido,
nitro, or amino group on the aryl ring before cyclization. In
addition, Pd-catalyzed arylation of benzotriazoles9 and N-
arylation of benzotriazole with benzyne10 gave a mixture of N1-
and N2-arylation products.
A number of azobenzenes 2 were examined to expand the
scope of azobenzenes in Rh-catalyzed amidation using tosyl
azide (Table 2). Azobenzene 2b having a 2-methyl group on
the phenyl ring was selectively converted to the monoamidated
For this reason, the selective synthesis of 2-aryl-2H-
benzotriazoles has been continuously in demand. In our
continuing efforts to develop efficient C−H activations,11 we
report herein an efficient synthetic method for 2-aryl-2H-
Received: March 21, 2014
Published: May 14, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
a
symmetric azobenzenes 2k and 2l were selectively amidated on
an unsubstituted phenyl ring (entries 10 and 11).
Table 1. Optimization of Amidation of Azobenzene
Next, the variation of the substituent at the S of sulfonyl
azides 1 was investigated in the reaction with 2c using
[Cp*RhCl2]2 (4 mol %) as the catalyst (Table 3). Phenyl, 4-
b
additive
1a:2a
temp
yield
(%)
entry
(mol %)
(equiv)
solvent
(°C)
a
Table 3. Scope of Sulfonyl Azides
1
AgSbF6 (16)
AgSbF6 (16)
AgSbF6 (16)
AgSbF6 (16)
AgSbF6 (16)
AgNTf2 (16)
AgBF4 (16)
AgPF6 (16)
AgOTf (16)
AgNTf2 (16)
AgNTf2 (16)
AgNTf2 (16)
AgNTf2 (16)
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1:1
t-AmOH
dioxane
PhCl
THF
110
110
110
110
110
110
110
110
110
110
110
110
90
7
2
34 (5)
11
3
4
39 (11)
60 (18)
66 (18)
45 (6)
35
5
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
entry
R
product
yield (%)
6
1
2
3
4
5
6
7
8
Ph
1b
1a
1c
1d
1e
1f
3m
3c
3n
3o
3p
3q
3r
89
92
93
91
56
54
60
61
7
4-MeC6H4
4-MeOC6H4
4-CF3C6H4
4-NO2C6H4
Me
8
9
17
10
11
12
13
55 (19)
71 (14)
72 (10)
1:1.2
1:1.5
1:2
c
c
n-Bu
1g
1h
85 (3)
Bn
3s
a
2a (0.2 mmol, entries 1−10), 1a (0.2 mmol, entries 11−13) in
a
b
solvent (1.0 mL) for 12 h. 1H NMR yields using CH2Br2 as an
Reaction conditions: 1 (0.2 mmol), 2c (0.24 mmol, 1.2 equiv),
1
[Cp*RhCl2]2 (4 mol %), and AgNTf2 (16 mol %) in DCE (1.0 mL) at
110 °C for 12 h.
internal standard. Numbers in parentheses are H NMR yields of 4a.
c
Isolated yield.
a
methoxyphenyl, and 4-trifluoromethylphenylsulfonyl azides
1b−d were all suitable substrates in the amidation reaction
(entries 1, 3, and 4). However, 4-nitrophenylsulfonyl azide 1e
gave the amidated product 3p in 56% yield (entry 5). Although
alkylsulfonyl azides were less reactive than arylsulfonyl azides in
the amidation reaction, the amidated azobenzenes were
obtained in acceptable yields (entries 6−8).
We next carried out the oxidative cyclization of tosylamino
azobenzene 3a to obtain 2-phenyl-2H-benzotrizole 5a (Table
4). Among the oxidants tested, PhI(OAc)2 (2.0 equiv) gave the
best result (entry 3). Under the optimal conditions, 5a was
obtained in 95% yield in toluene at 40 °C after 22 h.
Table 2. Scope of Azobenzenes
b
entry
R1
R2
2-Me
method
product
yield (%)
1
2-Me
3-Me
4-Me
2-Et
B
B
A
B
A
A
B
B
A
A
A
3b
3c
3d
3e
3f
82
92
87
83
84
77
79
87
79
65
56
2
3-Me
3
4-Me
4
2-Et
5
4-MeO
4-Cl
4-MeO
4-Cl
6
3g
3h
3i
7
3-Br
3-Br
Table 4. Optimization of Cyclization
8
3-Ac
4-CO2Et
H
3-Ac
9
4-CO2Et
3,5-(Me)2
3,5-(CF3)2
3j
10
11
3k
3l
H
a
Method A: 1a (0.2 mmol), 2 (0.4 mmol), [Cp*RhCl2]2 (4 mol %),
and AgNTf2 (16 mol %) in DCE (1.0 mL) at 90 °C for 12 h. Method
B: 1a (0.2 mmol), 2 (0.24 mmol), [Cp*RhCl2]2 (4 mol %), and
AgNTf2 (16 mol %) in DCE (1.0 mL) at 110 °C for 12 h. Isolated
entry
oxidant (equiv)
solvent
temp (°C)
yield (%)
b
1
2
3
4
PhI(OAc)2 (1.1)
PhI(OAc)2 (1.5)
PhI(OAc)2 (2.0)
Cu(OAc)2·H2O (3.0)
toluene
toluene
toluene
CH3CN
40
40
40
80
70
85
95
50
yields.
azobenzene 3b in 82% yield under the modified conditions (use
of 1.2 equiv of 2) (entry 1). Gratifyingly, the diamidated
products were not observed. 3-Methyl-substituted azobenzene
2c was selectively transformed to the amidated products 3c
having a tosylamino group at the 6-position in 92% yield due to
steric hindrance (entry 2). It is noteworthy that 4-methyl-
azobenzene underwent the selective monoamidation (entry 3).
In the case of 4-methoxy azobenzene 2f, the desired product 3f
was regioselectively obtained in 84% yield without diamidation
(entry 5). Functional groups commonly used in synthetic
chemistry were totally inert. For example, azobenzenes
possessing a chloro, bromo, ketone, and ester group were
selectively amidated to produce the amidated azobenzenes in
good to excellent yields (entries 6−9). Next, the challenging
amidation of unsymmetric substrates was investigated. Un-
Encouraged by these results, the substrate scope of a range of
substituents to cyclize with PhI(OAc)2 was studied (Scheme 2).
Electronic variation of substituents at the arene moiety of
azobenzenes 3 did not have an effect on the reaction efficiency.
3- and 4-Methyl-6-tosylamino azobenzenes 3c and 3d were
smoothly oxidized to provide the corresponding 2-aryl-2H-
benzotrizoles 5c and 5d in high yields. Azobenzenes 3b and 3e
having a 2-methyl- and 2-ethyl-5-tosylamino group underwent
the oxidative cyclization to produce 5b (95%) and 5e (99%). 2-
(4′-Methoxyphenyl)-2H-benzotrizole 5f having an electron-
donating methoxy group was obtained in good yield. The
reaction was highly chemoselective in that chloro, bromo,
ketone, and ester groups were tolerated. The present method
worked equally well even though with unsymmetric azoben-
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Organic Letters
Letter
a
ester on the phenyl ring underwent the sequential Rh-catalyzed
amidation and oxidation, leading to a two-component one-pot
synthesis of 2-aryl-2H-benzotrizoles 5 in reasonable yields.
Because 2-aryl-2H-benzotrizoles were fluorescent, their
optical properties in CH2Cl2 solution were examined (Table
6). The benzotrizole fluorophores showed large Stokes shifts
Scheme 2. Scope of Tosylamino Azobenzenes
a
Table 6. Photophysical Properties of Benzotriazoles
compd
λmax,abs (nm)
λmax,em (nm)
ε (M−1 cm−1
)
ϕ
5a
5b
5c
5d
5e
5f
309
291
313
315
290
334
318
321
315
332
312
309
365
376
361
365
372
387
368
nd
26 929
24 021
27 232
29 305
18 179
27 231
29 382
30 310
36 471
29 156
26 629
27 593
0.47
0.17
0.55
0.51
0.17
0.57
0.37
−
5g
5h
5i
nd
−
a
5j
368
361
379
0.56
0.45
0.16
3 (0.1 mmol) and PhI(OAc)2 (0.2 mmol) were used.
5k
5l
zenes. The oxidative cyclization of azobenzenes 3k and 3l
having dimethylphenyl and di(trifluoromethyl)-phenyl group
proceeded effectively to afford the desired 2-aryl-2H-benzo-
trizoles 5k and 5l in high yields.
As an extension of this work, we conducted a two-
component one-pot synthesis of 2-aryl-2H-benzotrizole 5
from tosyl azide 1a and azobenzenes 2 (Table 5). Azobenzene
a
Absorption peaks (λmax,abs) and molar extinction coefficients (ε) were
measured in CH2Cl2 (10−4 M). Full spectra are given in the SI.
(∼60 nm) and high extinction coefficients (∼3 × 104 M−1
cm−1), which is an attractive property for biological probes (see
SI).
We carried out KIE studies to gain insight into the reaction
mechanism (eq 1). A notable primary KIE was detected (kH/kD
Table 5. One-Pot Synthesis of Benzotriazoles Starting from
Azobenzenes and Tosyl Azides
a b
,
entry
5
method yield (%) entry
5
method yield (%)
= 2.1),13 indicating that the C−H bond cleavage at the ortho
position of azobenzene is most likely involved with the rate-
determining step.
c
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
A
B
B
A
B
A
80 (80)
76
7
5g
5h
5i
A
B
B
A
A
A
72
8
68
73
9
76
c
c
A plausible mechanism for the sequential Rh-catalyzed
76 (81)
70
10
11
12
5j
76 (77)
45
amidation and oxidation is described in Scheme 3.14 First,
5k
5l
77
59
a
Scheme 3. A Plausible Mechanism of Amidation
Method A: 1a (0.2 mmol), 2 (0.4 mmol), [Cp*RhCl2]2 (4 mol %),
and AgNTf2 (16 mol %) in DCE (1.0 mL) at 90 °C for 12 h. Method
B: 1a (0.2 mmol), 2 (0.24 mmol), [Cp*RhCl2]2 (4 mol %), and
b
AgNTf2 (16 mol %) in DCE (1.0 mL) at 110 °C for 12 h. PhI(OAc)2
(0.4 mmol). 1a (2.0 mmol), 2 (4.0 mmol), [Cp*RhCl2]2 (4 mol %),
c
and AgNTf2 (16 mol %) in DCE (10 mL) at 90 °C for 12 h.
2a (0.40 mmol) was treated with tosyl azide 1a (0.20 mmol) in
the presence of [Cp*RhCl2]2 (4 mol %) and AgNTf2 (16 mol
%) in DCE at 90 °C under aerobic conditions. After the
consumption of 1a for 12 h, PhI(OAc)2 (0.4 mmol) was added
to the reaction mixture and then the mixture was subsequently
stirred at 40 °C for an additional 22 h, producing 2-phenyl-2H-
benzotriazole 5a in 80% yield. To demonstrate the applicability
of the present method to larger scale processes, a reaction of a
2.0 mmol scale of 1a was undertaken with 2a (4.0 mmol). The
semi-one-pot reaction smoothly proceeded, and the corre-
sponding trizole 5a was isolated in 80% yield (312.0 mg).
Azobenzenes 2 having not only electron-donating groups such
as methyl, ethyl, and methoxy but also electron-withdrawing
groups such as chloro, bromo, trifuloromethyl, ketone, and
exposure of [Cp*RhCl2]2 to AgNTf2 affords a cationic Rh(III)
species, which assists the C−H activation to provide a five-
membered rhodacycles A. Coordination of N-sulfonyl azide 1
to A followed by insertion of a sulfonamido moiety into the
rhodacycle provides Rh(III) amido complex C. Finally,
protonolysis of C produces the desired amidated product 3.
Because the oxidation of tosylamino azobenzenes 3 to the
corresponding 2-aryl-2H-benzotriazoles 5 could be quenched in
the presence of TEMPO as a free radical scavenger, the
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Organic Letters
Letter
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(Scheme 4).8
Scheme 4. A Plausible Mechanism of Oxidative Cyclization
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In this paper, we have developed a selective synthetic method
of 2-aryl-2H-benzotriazoles from nonprefunctionalized azoben-
zenes and N-sulfonyl azides through sequential rhodium-
catalyzed amidation (C−N bond formation) and oxidation
(N−N bond formation) in one pot. The present method
enables the preparation of an array of 2-aryl-2H-benzotriazoles
with varied substitution patterns for efficient optimization of
photophysical properties.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures, characterization data, and 1H and 13
C
(12) Papers reporting an amidation of azobenzene recently appeared:
(a) Wang, H.; Yu, Y.; Hong, X.; Tan, Q.; Xu, B. J. Org. Chem. 2014, 79,
3279. (b) Jia, X.; Han, J. J. Org. Chem. 2014, 79, 4180.
NMR spectra for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
(13) (a) Jones, W. D. Acc. Chem. Res. 2003, 36, 140. (b) Kakiuchi, F.;
Matsuura, Y.; Kan, S.; Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936.
(14) (a) Kim, J. Y.; Park, S. H.; Ryu, J.; Cho, S. H.; Kim, S. H.;
Chang, S. J. Am. Chem. Soc. 2012, 134, 9110. (b) Ryu, J.; Shin, K.;
Park, S. H.; Kim, J. Y.; Chang, S. Angew. Chem., Int. Ed. 2012, 51, 9904.
(c) Kim, H. J.; Ajitha, M. J.; Lee, Y.; Ryu, J.; Kim, J.; Lee, Y.; Jung, Y.;
Chang, S. J. Am. Chem. Soc. 2014, 136, 1132. (d) Park, S. H.; Kwak, J.;
Shin, K.; Ryu, J.; Park, Y.; Chang, S. J. Am. Chem. Soc. 2014, 136, 2492.
(e) Kang, T.; Kim, Y.; Lee, D.; Wang, Z.; Chang, S. J. Am. Chem. Soc.
2014, 136, 4141.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: phlee@kangwon.ac.kr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Research Foundation
of Korea (NRF) grant funded by the Korea government
(MSIP) (2014001403).
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