Facile Cu(I)-catalyzed oxidative coupling of anilines to azo compounds and hydrazines with diaziridinone under mild conditions

Article abstract of DOI:10.1021/ol4005917

A mild and highly efficient Cu(I)-catalyzed oxidative coupling of anilines is described. Various primary and secondary anilines can be efficiently coupled under mild conditions to the corresponding azo compounds and hydrazines in high yields. This method provides a direct and practical access to these compounds and is also amenable to gram scale with no special precautions to exclude air or moisture.

Full text of DOI:10.1021/ol4005917

ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Facile Cu(I)-Catalyzed Oxidative Coupling
of Anilines to Azo Compounds and
Hydrazines with Diaziridinone under
Mild Conditions
Yingguang Zhu and Yian Shi*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523,
United States
yian@lamar.colostate.edu
Received March 4, 2013
ABSTRACT
A mild and highly efficient Cu(I)-catalyzed oxidative coupling of anilines is described. Various primary and secondary anilines can be efficiently
coupled under mild conditions to the corresponding azo compounds and hydrazines in high yields. This method provides a direct and practical
access to these compounds and is also amenable to gram scale with no special precautions to exclude air or moisture.
Development of efficient methods for the synthesis of
azo compounds is highly important as this class of mole-
cules can be used as organic dyes,1 indicators,2 radical
reaction initiators,3 nonlinear optics,4 chemosensors,5
and photochemical switches.6 Various synthetic methods7
have been developed including oxidation of hydrazines,8
reduction of azoxybenzenes,9 coupling of aryl diazonium
salts with nucleophiles,10 coupling of primary anilines with
(6) (a) Kumar, G. S.; Neckers, D. C. Chem. Rev. 1989, 89, 1915. (b)
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r
10.1021/ol4005917
XXXX American Chemical Society

aromatic nitroso compounds,11 and reductive coupling of
nitroaromatics.12 Azo compounds can also be obtained by
oxidative coupling of anilines using stoichiometric oxi-
dants, such as mercury(II) oxide,13 manganese salts,14 lead
tetraacetate,15 ferrate salts,16 and tert-butyl hypoiodite.17
Metal-catalyzed oxidative coupling of anilines using O2
has also been reported.18
In our earlier studies, di-tert-butyldiaziridinone (1)19,20
has been shown to be a highly effective nitrogen source for
the diamination of olefins using Pd(0)21 or Cu(I)22 as
catalysts. Very recently, we have shown that diaziridinone
1 can oxidize alcohols to aldehydes and ketones using
CuBr as catalyst.23 In our efforts to further explore the
synthetic utility of diaziridinone, we have found that
anilines can be efficiently oxidized to azo compounds
and hydrazines using CuBr catalyst and diaziridinone 1.
Herein we wish to report our preliminary results on this
subject.
When phenylamine (2a) was treated with di-tert-butyl-
diaziridinone (1) and 5 mol % of CuBr in CH3CN at rt
under air for 2 h, azobenzene 3a was cleanly formed and
isolated in 93% yield (Scheme 1). Similar yield (94%) was
obtained when this reaction was carried out under argon.
Both di-tert-butyldiaziridinone (1) and Cu(I) catalyst are
required for the transformation as no oxidation was ob-
served in the absence of 1 or CuBr under air for 24 h
(Scheme 1).
As shown in Scheme 2, this oxidative coupling can be
extended to a variety of primary anilines bearing either
electron-donating or electron-withdrawing groups at the
para, meta, and ortho positions on the phenyl ring, giving
the corresponding azo compounds in 70ꢀ98% yield
(Scheme 2, 3aꢀ3n). Halo-substituted azobenzenes can be
obtained in high yields from the corresponding anilines,
and no Ullmann-type CꢀN coupling byproducts were
detected (Scheme 2, 3jꢀ3l). As illustrated in the case of
4-bromoaniline (2l), azo product 3l can be obtained on
gram scale in 91% yield (Scheme 2). As shown in Scheme 3,
the oxidative coupling of aniline proceeded faster than the
oxidation of an alcohol. Azobenzene 3o was obtained
when 2o was treated with 1.1 equiv of diaziridinone 1
and 10 mol % of CuBr in CH3CN at rt for 2 h. Both amine
and alcohol were oxidized with 2.1 equiv of 1, giving
diketone 3o0 in 91% yield.
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Scheme 1
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B
Org. Lett., Vol. XX, No. XX, XXXX

Scheme 2. Oxidative Coupling of Primary Anilinesa,b
Scheme 3
hydrazine precursors.24,25 There are few methods reported
in the literature for the direct synthesis of substituted
hydrazines from readily available secondary anilines.26
The current method provides a viable process for the
synthesis of tetrasubstituted hydrazines.
In order to better understand the mode of reactivity,
1,2-diphenylhydrazine (6a) was subjected to the reaction
conditions. Azobenzene 3a was obtained in 96% yield in
only 5 min (Scheme 5), suggesting that 6a is a possible inter-
mediate for the oxidative coupling of aniline. Attempts to
isolate intermediate 6a in the coupling of aniline 2a using
0.55 equiv of 1 proved unsuccessful, yielding azobenzene
3a in 47% yield along with unreacted starting material
(Scheme 5).
While a precise understanding of the reaction mecha-
nism awaits further study, a plausible catalytic pathwayfor
the oxidative coupling of anilines is proposed in Scheme 6.
The NꢀN bond of di-tert-butyldiaziridinone (1) is reduc-
tively cleaved by CuBr to form Cu(II) nitrogen radical
A27,28 and/or Cu(III) species B,22e,f which reacts with
(25) For leading references on the synthesis of substituted hydrazines
€
a All reactions were carried out with primary aniline 2 (0.80 mmol),
1 (0.88 mmol), and CuBr (0.040 mmol) in CH3CN (1.6 mL) at rt for
2 h unless otherwise stated. b Isolated yield based on primary aniline 2.
c The reaction was carried out on 8.0 mmol scale.
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Ragnarsson, U. Angew. Chem., Int. Ed. Engl. 1996, 35, 2626. (b) Alberti,
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A.; Cane, F.; Dembech, P.; Lazzari, D.; Ricci, A.; Seconi, G. J. Org.
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Chem. 1996, 61, 1677. (c) Grehn, L.; Lonn, H.; Ragnarsson, U. Chem.
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60% yield (Scheme 4). This coupling process is also
applicable to various other secondary anilines, giving the
corresponding tetrasubstituted hydrazines in 54ꢀ99%
yield (Scheme 4, 5bꢀ5g). As illustrated in the case of
bis(4-bromophenyl)amine (4f), hydrazine 5f can be ob-
tained on gram scale in 99% yield (Scheme 4). Hydrazines
are a class of very important compounds.24 Substituted
hydrazines are usuallypreparedby derivatization of simple
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Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 4. Oxidative Coupling of Secondary Anilinesa,b
Scheme 5
Scheme 6. Proposed Catalytic Cycle for the Oxidative Coupling
a All reactions were carried out with secondary aniline 4 (0.80 mmol),
1 (0.88 mmol), and CuBr (0.040 mmol) in CH3CN (1.6 mL) at rt for 2 h
unless otherwise stated. b Isolated yield based on secondary aniline 4.
c The reaction was carried out on 8.0 mmol scale.
aniline 2 to generate the corresponding nitrogen radical
C28 and/or Cu(III) species D. Hydrazine 6 is subsequently
formed via the dimerization of radical C or reductive
elimination of species D. The dehydrogenation of 6 by
Cu species A and/or B forms product 3.
In summary, we have developed a novel oxidative coupl-
ing of anilines using CuBr as catalyst and di-tert-butyldia-
ziridinone (1) as oxidant. Various primary and secondary
anilines can be efficiently coupled under mild condi-
tions to give the corresponding azo compounds and
hydrazines in high yields. This reaction is operationally
simple and is amenable to gram scale. The results
further illustrate the synthetic potential of diaziridi-
none as a versatile oxidation reagent. Development of
other reaction processes with this class of compounds is
currently underway.
Acknowledgment. We are grateful for the generous
financial support from the General Medical Sciences of
the National Institutes of Health (GM083944-05).
Supporting Information Available. Experimental pro-
cedures, characterization data, and NMR spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX