Angewandte
Chemie
DOI: 10.1002/anie.201202786
Synthetic Methods
Oxidative Dimerization of Aromatic Amines using tBuOI: Entry to
Unsymmetric Aromatic Azo Compounds**
Youhei Takeda, Sota Okumura, and Satoshi Minakata*
Aromatic azo compounds have found tremendous applica-
tions in industry as organic dyes, pigments, food additives,
indicators, and therapeutic agents.[1] Furthermore, by taking
advantage of their unique photochemical responsivity, the
potential applications of azo compounds have been extended
to a wide range of light-responsive functional materials (e.g.,
liquid crystals,[2] molecular photoswitches,[3] and photochro-
mic ligands for optochemical genetics[4]) over the past few
decades. Of the myriad of synthetic methods for aromatic azo
compounds,[5] conventional methods for symmetric aromatic
azo compounds involve reductive homodimerization of nitro-
arenes[6] and oxidation of aromatic amines.[5,7] Nevertheless,
these methods suffer from the stoichiometric use of environ-
mentally unfriendly transition-metal oxidants (e.g., Mn,[7a]
Pb,[7b] and Hg[7c,d] salts), or from difficulty in controlling
product distribution (e.g., the azo-/azoxybenzene ratio in the
reductive methods). In addition to these problems, great
challenges remain in the synthesis of unsymmetric aromatic
azobenzenes. Representative protocols for unsymmetric aro-
matic azo compounds involve diazo coupling[8] and the Mills
reaction.[9] These methods require the preparation of reactive
intermediates, that is, diazonium salts and nitroso compounds,
from commercially available compounds. More specifically,
the main issue of these approaches lies in the substrate scope,
which is limited to the combination of electron-rich and
electron-deficient aromatic amines because of their intrinsic
reaction mechanism. In this regard, a recent catalytic
oxidation of aromatic amines using oxygen as an oxidant
has been developed.[10,11] While Grirrane, Corma, and Garcꢀa
developed an oxidative dimerization of aniline derivatives
utilizing a Au/TiO2 catalyst,[10] Jiao and co-workers reported
a copper-catalyzed aerobic oxidative coupling of aromatic
amines.[11] Both succeeded in synthesizing a series of unsym-
metric azobenzenes by using their methods. Nonetheless, the
former method requires high pressures of O2 (5 bar) and high
temperatures (1008C), and the latter requires excess amounts
(5 equiv) of the electron-deficient aromatic amines to attain
sufficient yields of the unsymmetric azo products relative to
the symmetric products. Therefore, there still remains con-
siderable room for the development of synthetic methods for
unsymmetric aromatic azo compounds. Herein, we present an
efficient oxidative homo- and cross-dimerization reaction of
aromatic amines utilizing the organic oxidant tert-butyl
hypoiodite (tBuOI)[12] under mild reaction conditions (room
temperature or below), thus leading to a variety of symmetric
and unsymmetric aromatic azo compounds having high
functional-group tolerance (Scheme 1).
Scheme 1. Oxidative dimerization of aromatic amines using tBuOI.
As part of our research project to develop efficient
synthetic methods for heterocycles utilizing Q-halogen-con-
taining reagents (Q = O, N),[13] we have demonstrated that
tBuOI is a powerful iodinating reagent for compounds
bearing acidic hydrogen atoms, such as oximes, carboxamides,
À
and sulfonamides, to generate unique species having Q I
bonds; such species serve as the key intermediates in the
synthetic reactions.[14] On the basis of this background, we
envisioned that oxidative dimerization of anilines, which have
two relatively weakly acidic hydrogen atoms, would be
feasible by utilizing tBuOI. Namely, the treatment of anilines
with tBuOI would generate ArNI2 through a hydrogen–iodine
exchange process, and the subsequent elimination of 2HI
from ArNI2 and unreacted ArNH2 should produce symmetric
aromatic azo compounds (Scheme 1). Specifically, given that
two different anilines are used, the aniline having the more
acidic hydrogen atoms (Ar1NH2) should undergo iodination
prior to the other (Ar2NH2). We hypothesized that nucleo-
philic substitution at the nitrogen atom of Ar1NI2 with the
remaining Ar2NH2 would selectively give the unsymmetric
azo product over the homodimer.
[*] Dr. Y. Takeda
Frontier Research Base for Global Young Researchers
Graduate School of Engineering
Osaka University, Osaka 565-0871 (Japan)
Dr. Y. Takeda, S. Okumura, Prof. Dr. S. Minakata
Department of Applied Chemistry, Graduate School of Engineering
Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871 (Japan)
E-mail: minakata@chem.eng.osaka-u.ac.jp
To verify our hypothesis, we examined an oxidative
homodimerization of aniline (1a) in the presence of
tBuOI.[15] When 0.5 mmol of 1a was treated with tBuOI
(1.0 mmol) in acetonitrile at room temperature for 1 hour,
[**] This research was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas, “Molecular Activation Directed
toward Straightforward Synthesis”, from the MEXT (Japan). Y.T.
acknowledges support from the Frontier Research Base for Global
Young Researchers, Osaka University, from the Program of MEXT.
=
oxidative homodimerization to form a N N bond smoothly
proceeded to give trans-azobenzene (2aa) in 95% yield
(Table 1).[16]
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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