Palladium-catalyzed direct ortho-nitration of azoarenes using NO2 as nitro source

Article abstract of DOI:10.1021/ol502090n

A palladium-catalyzed direct ortho-nitration reaction of azoarenes was developed in which NO₂ was used as both nitro source and oxidant for the first time. The nitration products were converted into o-aminoazoarenes or benzotriazole derivatives by a simple reduction.

Full text of DOI:10.1021/ol502090n

Letter
pubs.acs.org/OrgLett
Palladium-Catalyzed Direct Ortho-Nitration of Azoarenes Using NO2
as Nitro Source
Jiawei Dong,† Bo Jin,† and Peipei Sun*,†,‡
†Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing
210097, China
‡Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Nanjing 210023, China
S
* Supporting Information
ABSTRACT: A palladium-catalyzed direct ortho-nitration
reaction of azoarenes was developed in which NO2 was used
as both nitro source and oxidant for the first time. The
nitration products were converted into o-aminoazoarenes or
benzotriazole derivatives by a simple reduction.
zoarenes are an important class of synthetic coloring
agents in the dye industry. The role of the structural
significant challenge. Continuous interest in developing
convenient routes for the construction of carbon−carbon and
carbon−heteroatom bonds prompted us to study such a
nitration protocol. Now we report the palladium-catalyzed
direct ortho-nitration to azoarenes, in which NO2 as a “clean”
nitro source was first used in the transition metal-catalyzed C−
H bond functionalization. The nitration products were
converted into o-amino azoarenes or benzotriazole derivatives
by a simple reduction.
A
factors, such as the number of azo moieties, the nature of the
aromatic ring, and the nature, position, and number of
substituents on dye properties have been intensively studied.1
The character of the light-driven reversible isomerization
between their cis and trans forms makes them excellent
candidates to modulate the relative movement of different
moieties;2 therefore, azoarenes are widely used in many newly
rising areas of science, such as photochemical molecular switch,
supermolecular chemistry of host−guest recognition, self-
assembly liquid crystal material, analysis of biomedical imaging,
and chemical and light-driven molecular motors.3 A review for
the synthesis of azoarenes is available.4 In the past decade,
transition-metal-catalyzed chelation-assisted inert C−H bond
functionalization has become a remarkable strategy in the
construction of a variety of carbon−carbon or carbon−
heteroatom bonds with features of step-economics and green
chemistry.5 With this concept, a series of modifications to
azoarenes were developed, e.g., Pd-catalyzed ortho-acylation
using aldehydes, α-oxocarboxylic acids or toluene derivatives as
the acyl sources,6 Rh-catalyzed annulation with alkynes,7 Rh-
catalyzed C−H bond addition of azoarenes to aldehydes and
subsequent formation of indazoles,8 Rh-catalyzed amidation
with N-sulfonyl azides,9 Pd-catalyzed ortho-alkoxylation with
alcohols,10 and Ru-catalyzed alkenylation of azoxybenzenes
with alkenes.11
We performed our study with the direct ortho-nitration of
azobenzene (1a), and the results are assembled in Table 1.
NaNO2 (2 equiv) was initially selected as the nitro source.
Without the catalyst, the reaction could not take place at all
(entry 1). Thus, Pd(OAc)2 (10 mol %) was employed as the
catalyst. An oxidant was also essential to this transformation. In
the presence of oxone or K2S2O8, the reaction gave the desired
product 2a in 42% and 10% yield in 12 h, respectively (entries 2
and 3), while the addition of 3 equiv of HOAc increased the
yield to 80% when K2S2O8 was used (entry 4). We then used
NO2 as the nitro source. To our delight, compared with
NaNO2, the nitration with NO2 to 1a gave the corresponding
product 2a in a higher yield of 85% in 6 h (entry 5). Without
the oxidant, a similar yield of 87% was obtained (entry 6). NO2
was then selected for our present nitration reaction. Several
solvents (CH3CN, dioxane, toluene, and DCE) were tested,
and DCE gave the best results (entries 6−9). The screening of
the reaction temperature was also carried out and the suitable
temperature was proved to be 90 °C (entries 6 and 10).
Using the optimized reaction conditions, we then explored
the substrate scope of this Pd-catalyzed ortho-nitration of
azoarenes. The results are summarized in Scheme 1. For the
symmetrical azoarenes, the substrates with a range of
substituents on the benzene ring were tested. The results
revealed that the reaction had good compatibility with several
It is well-known that the nitro group can affect the properties
of the organic compounds by its strong electron-withdrawing
character. Nitro compounds are also key materials for preparing
dyes, plastics, explosives, pharmaceuticals, and many other
useful compounds.12 Several transition-metal-catalyzed chela-
tion-assisted ortho-nitrations of aromatic C−H bonds have been
reported for the synthesis of this class of compounds in recent
years.13 Very recently, a direct metal-free nitro-carbocyclization
of activated alkenes was also described.14 Still, to establish a
cheap, efficient, and atom-economic nitration method is a
Received: July 16, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol502090n | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Optimization of the Reaction Conditions
Scheme 1. Results of the Nitration Reaction of Azobenzene
b
entry nitro source (equiv/atm) oxidant (equiv)
solvent
yield (%)
c
1
2
3
4
5
6
7
8
9
NaNO2 (2)
NaNO2 (2)
NaNO2 (2)
NaNO2 (2)
NO2 (1)
K2S2O8 (3)
oxone (3)
DCE
0
42
10
80
85
87
54
18
45
65
DCE
K2S2O8 (3)
K2S2O8 (3)
K2S2O8 (3)
DCE
d
DCE
DCE
NO2 (1)
DCE
NO2 (1)
CH3CN
dioxane
toluene
DCE
NO2 (1)
NO2 (1)
e
10
NO2 (1)
a
Unless otherwise specified, the reactions were carried out in a sealed
tube in the presence of azobenzene (1a) (0.5 mmol), NaNO2 (2
equiv), or NO2 (1 atm), Pd(OAc)2 (10 mol %), and oxidant (3 equiv)
in 2 mL of solvent at 90 °C for 12 h (using NaNO2) or 6 h (using
b
c
d
NO2). Isolated yield. Without catalyst. CH3COOH (3.0 equiv) was
e
added. At 70 °C.
functional groups, and the presence of alkyl, methoxyl, and halo
groups did not evidently affect the transformation. For most
substrates with these groups, high yields were obtained under
the standard reaction conditions (2c−l), and only the ortho-
substituted azobenzene gave the moderate yield because of the
steric effect (2b). However, with some electron-withdrawing
groups, such as acyl, trifluoromethyl showed inhibiting effect to
the reaction (2m,n). Surprisingly, azobenzene with two
electron-donating groups (OCH3) also gave lower yield (2o).
It is interesting that this C−H nitration of azoarenes with meta
substituents showed excellent regioselectivity. In any case, the
nitration occurred at the position para to the meta substituents.
A series of unsymmetrical azoarenes were then employed for
this ortho-nitration reaction (2p−v). For every substrate, the
reaction took place exclusively on the benzene ring with an
electron-donating group in moderate to good yields, which
further indicated that an electron-rich benzene ring was
favorable to the reaction.
Using the ortho-nitration product as the reactant, a further
transformation was studied. As shown in Scheme 2, 2-
nitroazobenzene (2a) was selected as the substrate, Zn power
was employed as a reducer, and NH4Cl was used as additive. In
methanol, a reduction product 2-aminoazobenzene (3a) was
obtained at 50 °C after 2 h in 93% yield. However, when the
reaction temperature was raised to 85 °C, a reductive
cyclization product 2-phenyl-2H-benzo[d][1,2,3]triazole (4a)
was generated in an excellent yield of 97% after 4 h.
a
Reaction conditions: 1 (0.5 mmol), Pd(OAc)2 (10 mol %), NO2 (1
b
atm), and the DCE (2 mL) in a sealed tube at 90 °C for 6 h. Isolated
yields. At 100 °C.
c
Scheme 2. Reduction of Ortho-Nitration Product of
Azobenzene
For understanding the mechanism of this palladium-
catalyzed nitration of the C(sp2)−H bond, we determined
the components of the gas generated from the reaction under a
limited amount of NO2 and air via GC−FTIR. From the
mixture, NO and N2O were detected, which suggested that
NO2 may also act as an oxidant except as the nitro source in
this transformation. Based on this assumption and the related
transition-metal-catalyzed ortho-nitration reactions of the
reported C(sp2)−H bond,13 a possible mechanism is proposed
(Scheme 3). First, the coordination of azo in azobenzene to
Pd(OAc)2 formed a cyclopalladated intermediate A; this
intermediate then underwent chelation with NO2 to form a
PdIII intermediate B. The oxidation of B by another NO2
generated the PdIV intermediate C. Finally, the reductive
elimination of C leads to the nitration product 2 with
regeneration of PdII to start the next cycle.
In summary, we have developed a simple method for the
direct ortho-nitration of azoarenes via a Pd-catalyzed azo group
B
dx.doi.org/10.1021/ol502090n | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(4) Hamon, F.; Djedaini-Pilard, F.; Barbot, F.; Len, C. Tetrahedron
2009, 65, 10105.
Scheme 3. Proposed Mechanism for Pd-Catalyzed Nitration
of C(sp2)−H Bond
(5) For partial recent reviews, see: (a) Yeung, C. S.; Dong, V. M.
Chem. Rev. 2011, 111, 1215. (b) Sun, C. L.; Li, B. J.; Shi, Z. J. Chem.
Rev. 2011, 111, 1293. (c) Liu, C.; Zhang, H.; Shi, W.; Lei, A. W. Chem.
Rev. 2011, 111, 1780. (d) Davies, H. L.; Bois, J. D.; Yu, J. Q. Chem. Soc.
Rev. 2011, 40, 1855 and other reviews in this themed issue. (e) Li, B.
J.; Shi, Z. J. Chem. Soc. Rev. 2012, 41, 5588. (f) Neufeldt, S. R.;
Sanford, M. S. Acc. Chem. Res. 2012, 45, 936. (g) Li, B.; Dixneuf, P. H.
Chem. Soc. Rev. 2013, 42, 5744. (h) Wu, Y. N.; Wang, J.; Mao, F.;
Kwong, F. Y. Chem.Asian J. 2014, 9, 26.
(6) (a) Li, H. J.; Li, P. H.; Wang, L. Org. Lett. 2013, 15, 620. (b) Li,
H. J.; Li, P. H.; Tan, H.; Wang, L. Chem.Eur. J. 2013, 19, 14432.
(c) Li, Z. Y.; Li, D. D.; Wang, G. W. J. Org. Chem. 2013, 78, 10414.
(d) Song, H. Y.; Chen, D.; Pi, C.; Cui, X. L.; Wu, Y. J. J. Org. Chem.
2014, 79, 2955.
(7) Muralirajan, K.; Cheng, C. H. Chem.Eur. J. 2013, 19, 6198.
(8) Lian, Y.; Bergman, R. G.; Lavis, L. D.; Ellman, J. A. J. Am. Chem.
Soc. 2013, 135, 7122.
(9) Ryu, T.; Min, J.; Choi, W.; Jeon, W. H.; Lee, P. H. Org. Lett.
2014, 16, 2810. (b) Jia, X. F.; Han, J. J. Org. Chem. 2014, 79, 4180.
(10) Yin, Z. W.; Jiang, X. Q.; Sun, P. P. J. Org. Chem. 2013, 78,
10002.
(11) Li, H. J.; Xie, X. Y.; Wang, L. Chem. Commun. 2014, 50, 4218.
(12) (a) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH:
Weinheim, 2001. (b) Adams, J. P.; Paterson, J. R. J. Chem. Soc., Perkin
Trans. 1 2000, 3695. (c) Ballini, R.; Petrini, M. Tetrahedron 2004, 60,
1017.
directed sp2 C−H bond activation using NO2 as the nitro
source. The reaction exhibited good functional group tolerance,
and a series of azobenzene derivatives with either electron-
donating or electron-withdrawing groups were nitrated directly
and efficiently. The nitration products were reduced to o-
aminoazoarenes or benzotriazole derivatives by zinc. This
protocol provided a convenient and atom-economic route for
the syntheses of 2-nitroazoarenes and related compounds and
therefore is an important extension of the chemistry of azo
compounds.
(13) (a) Liu, Y. K.; Lou, S. J.; Xu, D. Q.; Xu, Z. Y. Chem. −Eur. J.
2010, 16, 13590. (b) Zhang, L.; Liu, Z. H.; Li, H. Q.; Fang, G. C.;
Barry, B. D.; Belay, T. A.; Bi, X. H.; Liu, Q. Org. Lett. 2011, 13, 6536.
(c) Xie, F.; Qi, Z. S.; Li, X. W. Angew. Chem., Int. Ed. 2013, 52, 11862.
(d) Li, Y. X.; Li, L. H.; Yang, Y. F.; Hua, H. L.; Yan, X. B.; Zhao, L. B.;
Zhang, J. B.; Ji, F. J.; Liang, Y. M. Chem. Commun. 2014, 50, 9936.
(e) Katayev, D.; Pfister, K. F.; Wendling, T.; Gooßen, L. J. Chem.
Eur. J. 2014, 20, 9902. (f) Majhi, B.; Kundu, D.; Ahammed, S.; Ranu,
B. C. Chem.Eur. J. 2014, 20, 9862.
ASSOCIATED CONTENT
* Supporting Information
■
S
(14) Shen, T.; Yuan, Y. Z.; Jiao, N. Chem. Commun. 2014, 50, 554.
Experimental procedures and full characterization for all
compounds; copies of 1H NMR and 13C NMR for all
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: sunpeipei@njnu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (Project Nos. 21272117 and 20972068)
and the Priority Academic Program Development of Jiangsu
Higher Education Institutions.
REFERENCES
■
(1) (a) Griffiths, J. Chem. Soc. Rev. 1972, 1, 481. (b) Venkataraman,
K. The Chemistry of Synthetic Dyes; Academic Press: New York, 1956.
(2) Bandara, H. M. D.; Burdette, S. C. Chem. Soc. Rev. 2012, 41,
1809.
(3) (a) Beharry, A. A.; Woolley, G. A. Chem. Soc. Rev. 2011, 40, 4422.
(b) Feringa, B. L.; Van Delden, R. A.; Koumura, N.; Geertsema, E. M.
Chem. Rev. 2000, 100, 1789. (c) Lee, S.; Kang, H. S.; Park, J. K. Adv.
́
Mater. 2012, 24, 2069. (d) García-Amoros, J.; Velasco, D. Beilstein J.
Org. Chem. 2012, 8, 1003. (e) Renner, C.; Moroder, L. ChemBioChem
2006, 7, 868. (f) Natansohn, A.; Rochon, P. Chem. Rev. 2002, 102,
4139.
C
dx.doi.org/10.1021/ol502090n | Org. Lett. XXXX, XXX, XXX−XXX