For the synthesis of nitrosoarenes from anilines a
number of suitable oxidation methods have been pub-
lished in recent years employing, e.g., the oxidizing
agents Caro’s acid (peroxomonosulfuric acid), peracetic
acid, 3-chloroperoxybenzoic acid (m-CPBA), or potassium
permanganate.8 The application of hydrogen peroxide in
the presence of rhenium,9 tungsten,10 or molybdenum11
catalysts was reported to give high yields of the nitroso
compounds on a 1-10 mmol scale. Side reactions during
the oxidation of anilines 1 are the formation of nitro
derivatives 6 due to further oxidation of the nitroso
compounds 2 and condensation reactions yielding azoben-
zenes 3 from the nitrosoarenes 2 and anilines 1 or
azoxybenzenes 4 from the N-arylhydroxylamine inter-
mediates 5 and anilines 1 (Scheme 1). General observa-
Efficient Preparation of Nitrosoarenes for
the Synthesis of Azobenzenes†
Beate Priewisch and Karola Ru¨ck-Braun*
Technische Universita¨t Berlin, Institut fu¨r Chemie,
Strasse des 17. Juni 135, D-10623 Berlin, Germany
Received August 19, 2004
SCHEME 1
Reaction conditions are described for the oxidation of
anilines furnishing nitrosoarenes and the synthesis of un-
symmetrically substituted azobenzenes. In a comparative
study, the catalytic oxidation of methyl 4-aminobenzoate by
hydrogen peroxide was investigated, and SeO2 proved to be
superior or equal to methyl trioxorhenium (MTO) and
Na2WO4, respectively. Nevertheless, the application of the
inexpensive, environmentally friendly, Oxone in a biphasic
system proved to be more efficient, and a variety of useful
nitrosoarenes for the synthesis of azo compounds were
prepared in high yield and purity on a large scale.
Nitroso compounds undergo a variety of transforma-
tions of great potential such as nitroso aldol reaction,1
nitroso ene reaction,2 [2 + 2]2 and [4 + 2]3 cycloadditions,
additions of Grignard reagents,4 and coupling with
amines to yield azobenzenes.5 They are also used as spin
traps6 and were even studied as anti-retroviral agents
and antitumor agents.7
During our efforts to synthesize unsymmetrically
substituted azobenzenes from anilines and nitrosoarenes,
we became aware of a lack of simple high-yielding
procedures for the large-scale synthesis of nitrosoarenes
containing electron-withdrawing groups. We herein re-
port on catalytic oxidations by hydrogen peroxide and the
application of Oxone in a biphasic system.
tions and achievements can be summarized as follows:
Side reactions were commonly observed to a greater
extent for less reactive anilines with an electron-
withdrawing group in the para or meta position, espe-
cially during prolonged reaction times. Often, complex
reaction mixtures were obtained in larger quantity under
homogeneous reaction conditions as under heterogeneous
in catalytic oxidations with hydrogen peroxide. Two-
phase heterogeneous systems were found to secure the
separation of the generally less water-soluble nitroso
compounds 2 from the N-arylhydroxylamine intermedi-
ates 5 and the aniline precursors 1, and thus to prevent
condensation reactions. Reaction time, temperature, and
the pH value are of importance in order to optimize the
reaction conditions and product ratios.
† Dedicated to Prof. Horst Kunz on the occasion of his 65th birthday.
(1) (a) Oppolzer, W.; Tamura, O.; Sundarababu, G.; Signer, M. J.
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references therein.
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We first started a comparative study and investigated
the ability of methyl trioxorhenium (MTO), Na2WO4, and
SeO2 to catalyze the oxidation of methyl 4-aminobenzoate
1a by H2O2 furnishing 2a (Table 1). Espenson et al.
described the oxidation of donor-substituted anilines (∼10
(8) Gowenlock, B. G.; Richter-Addo, G. B. Chem. Rev. 2004, 104,
3315-3340 and references therein.
(9) Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 1326-1332.
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10.1021/jo048544x CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/11/2005
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