Manganese(III) acetate-mediated oxidative coupling of phenylhydrazines with benzene: A novel method for biaryl coupling

Article abstract of DOI:10.1039/b105119a

The reaction of phenylhydrazines with benzene in the presence of manganese(III) acetate affords biaryls in good yields. The same reaction was carried out with similar oxidants, such as Co^III, Ce^IV and Pb^IV; among these oxidants Mn^III acetate shows higher efficiency and selectivity.

Full text of DOI:10.1039/b105119a

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Manganese(III) acetate-mediated oxidative coupling of
phenylhydrazines with benzene: a novel method for biaryl coupling
Ayhan S. Demir,* Ömer Reis and Emine Özgül-Karaaslan
1
versatile reagent for oxidation of various types of organic
substrates.7 The oxidation of phenylhydrazine with barium
ferrate monohydrate in benzene yields biphenyl in 70% yield.
However, oxidation of p-nitrophenylhydrazine and 2,4-dinitro-
phenylhydrazine produced nitrobenzene and m-dinitrobenzene,
respectively, in good yields. Manganese dioxide was reported to
give m-nitrobenzene from 2,4-dinitrophenylhydrazine in 50%
yield.8 Formation of aryl radicals from arylhydrazines by CuII
salts and their subsequent reaction with alkenes were reported
where the reaction yields varying amounts of the corresponding
arenes and haloarenes.9 As a result, oxidation of arylhydrazines
by a variety of oxidizing agents is well known to provide arenes,
biaryls and azoarenes in varying amounts, depending on reac-
tion conditions. Despite the straightforward procedure and
easily available starting materials, oxidation of arylhydrazines
by the oxidants mentioned above cannot be an alternative to the
catalytic coupling reactions unless the yields are improved and
the reaction is free of side products.
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received (in Cambridge, UK) 11th June 2001, Accepted 7th September 2001
First published as an Advance Article on the web 29th October 2001
The reaction of phenylhydrazines with benzene in the presence of manganese() acetate affords biaryls in
good yields. The same reaction was carried out with similar oxidants, such as CoIII, CeIV and PbIV; among
these oxidants MnIII acetate shows higher efficiency and selectivity.
Introduction
C–C Bond-forming reactions leading to biaryls are very
important because this approach is the key step in the synthesis
of many natural and unnatural biaryls. There are various biaryl
coupling methods, and the applications of these methods are
reviewed comprehensively in the literature.1 Of these methods,
the Pschorr reaction and the GBH reaction (Gomberg–
Bachmann–Hey) utilize diazonium salts treated with copper
salts to effect coupling. In the classical Ullmann reaction, aryl
halides are treated with copper, forming the corresponding
biaryls. The original Ullmann reaction employs high temper-
atures and is greatly affected by the nature of the substituents
and the steric environment. An ambient-temperature variant
of this reaction was developed and has been used by many
researchers.2 Catalytic coupling reactions are also well known
in biaryl synthesis, the four most commonly used being the
Kharasch, Negishi, Stille and Suzuki reactions.3 Today catalytic
coupling reactions are routine means of access to biaryls in the
laboratory. In these catalytic coupling methods, the course of
reaction is determined by the position of the functional group
specific to the method employed so that regioselective coupling
is possible. Thus, the selectivity of the coupling site is now
reduced to the introduction of that functional group into the
desired coupling position.
The synthesis of biaryls from arylhydrazines by various oxid-
izing agents has been reported. The earliest one is the oxidation
of phenylhydrazine by mercuric [mercury()] oxide in which
aniline and biphenyl are isolated oxidation products.4 The
oxidation of phenylhydrazine with PbIV acetate in aromatic
solvents such as benzene, chlorobenzene, nitrobenzene and in
dichloromethane has been reported.5 At low temperatures in
dichloromethane the benzenediazonium ion was formed. At
room temperature, benzene, azobenzene, biphenyl and, where
aromatic solvents were used, biaryls were isolated products.
Reaction in benzene yields 37% biphenyl, 6% azobenzene and
trace amounts of phenyl acetate. Moreover, the same reaction
in nitrobenzene yields 30% benzene and 36% nitrobiphenyl
as well as trace amounts of azobenzene and phenyl acetate.
Similar results were reported when using chlorobenzene as
solvent. In another study, haloarenes were coupled with aryl-
hydrazines in methanol by either Pd or Pd–Hg catalyst.6 It was
reported that oxidized palladium was recovered by its reaction
with phenylhydrazine. The reaction yields biaryls resulting from
self-coupling of haloarenes as well as from cross-coupling with
arylhydrazines. The catalyst was formed in situ by action of
arylhydrazine on palladium chloride and mercury() chloride.
Barium ferrate monohydrate was offered as an alternative
Manganese triacetate is a one-electron oxidant, largely used
as a radical generator. Since the pioneering work of Heiba
and Bush in 1968,10 MnIII-mediated oxidations have been exten-
sively studied. Fristad showed that the rate of radical gener-
ation with Mn(OAc)3 with bridging acetates correlates with the
enolizability and CH acidity of the substrates.11 Thus it is this
reagent’s ability to generate radicals in such systems that leads
to highly efficient C–C bond-forming reactions, especially for
the construction of cyclic systems, a topic reviewed by Snider.12
Previously, we published several papers in the area of man-
ganese triacetate-mediated oxidation of ketones to form C–O
bonds.13
Since it is possible to form biaryls by the generation of aryl
radicals from arylhydrazines, we began investigating their oxid-
ation by manganese triacetate. Herein we report the formation
of biaryls via oxidation of hydrazines by manganese triacetate.
Results and discussion
At first, we examined the oxidation of phenylhydrazine in ben-
zene with manganese() acetate at room temperature as shown
in Scheme 1. A mixture of manganese() acetate and phenyl-
Scheme 1
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J. Chem. Soc., Perkin Trans. 1, 2001, 3042–3045
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b105119a

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hydrazine in benzene was stirred at room temperature and the
reaction was monitored by GC-MS. After 4 hours, 45% conver-
sion of phenylhydrazine to biphenyl was observed. Refluxing of
the same reaction mixture for one hour using a Dean–Stark
trap furnished biphenyl in 73% yield as the sole product with-
out any purification. No product formation was observed using
phenylhydrazinium chloride at RT. Refluxing was necessary to
obtain biphenyl from phenylhydrazinium chloride in 75% yield.
Consequently, the reaction is applicable for both arylhydrazines
and their salts without any complication. The highest yield was
obtained by using three equivalent of manganese() acetate.
We noticed that a slight excess of the oxidant secures the
highest yields. The yield of the reaction was satisfactory and,
contrary to the other reported oxidizing agents, was free
from azobenzene and other side products.
given substrate class gave similar product distribution. MnIII
acetate is more selective and effective than CoIII, CeIV and PbIV.
Selectivities can be attributed to the slow formation of radicals
with MnIII acetate. CoIII, CeIV and PbIV compounds are more
powerful oxidants, and therefore less selective.
In the oxidation of monoarylhydrazines with several oxidiz-
ing agents, the observed products have been explained in terms
of a generated phenyldiimide and its subsequent breakdown.
A similar mechanism that is proposed for PbIV acetate and CuII
is probably operating during the reaction, which is outlined in
Scheme 2.5,9 Azoarene products might result from the oxidation
After examination of the formation of biphenyl from phen-
ylhydrazinium chloride, other commercially available hydra-
zines were treated under the same reaction conditions. Of these
hydrazines, o-, m- and p-bromophenylhydrazine were used to
test the reaction’s applicability to different isomers. These
hydrazines have been shown to give the corresponding biphenyl
product without isomerization as observed by GC-MS and
NMR of crude products. Thus it is evident from these results
that the coupling occurs from the position where the hydrazine
moiety was originally substituted. Reactions with free hydra-
zines (1h, j and k) were complete in shorter times. Also exam-
ined were phenylhydrazines having electron-withdrawing and
electron-releasing groups at different positions. The results are
summarized in Table 1. The yields are affected by the position
of substitution. While p-bromophenylhydrazine gives an 81%
yield, the ortho isomer gives a 70% yield, and the highest yields
were attained with a strong electron-releasing group at the para
position.
When the oxidations were carried out in substituted benzene
solvents such as toluene and bromobenzene the corresponding
biaryls were obtained in good yields but no apparent selectivity
was observed for the formation of biaryls. As shown in Table 2
ortho- and para-products are obtained as major products.
Manganese() acetate bears many similarities, with respect
to a given substrate class, with other one-electron oxidants
like CoIII and CeIV, and some two-electron oxidants like PbIV.
For comparison, phenylhydrazine was treated with cerium()
ammonium nitrate (CAN), CoIII acetylacetonate and PbIV acet-
ate under similar conditions. Reaction of phenylhydrazine with
PbIV acetate gave two major products: biphenyl and azobenzene
(5 : 1) and a trace amount of phenyl acetate. The results of this
PbIV acetate reaction are comparable with previously reported
literature results.5 The reaction of phenylhydrazine with Co()
acetylacetonate gave two major products: biphenyl and pyra-
zole derivative 5 (3 : 1 respectively). Treatment of phenylhydra-
zine with CAN furnished a mixture of products. The major
fractions were identified as biphenyl and azobenzene (3 : 2
respectively). In addition to these compounds, complex mix-
tures of terphenyl isomers and azobenzene derivatives of
biphenyls were detected by GC-MS. As shown in Table 3, the
isolated yields of products are very low. In all cases there were
unidentifiable products.
Scheme 2
of hydrazobenzene which is produced by diazonium attack on
arylhydrazine to give tetrazene followed by loss of nitrogen as
proposed by Aylward.5 Theoretically, two equivalents of man-
ganeseIII acetate are needed for the oxidation but the best results
are obtained by using three equivalents of manganeseIII acetate.
The manganeseIII acetate used in this study was commercial and
dried over P2O5 prior to use. Alternatively it can be synthesized
from manganeseII nitrate and acetic anhydride.13a Since MnIII
acetate is a hydrate of unspecified composition and forms
manganese oxide hydrate with water,13g the exact content of
the MnIII acetate is uncertain. Hence, we arbitrarily used an
excess of MnIII acetate per mole substrate in our ongoing work.
Interestingly, we repeatedly observed that the use of only 3
equivalents of the oxidant was the best choice. This is a truly
remarkable result and warrants further experimentation.
In conclusion, we showed that it is possible to oxidize aryl-
hydrazines with MnIII acetate in benzene to form the corre-
sponding phenyl-substituted benzene derivatives in good yield;
access to biaryls works selectively, and coupling occurs where
hydrazine departs. Using substituted benzenes as solvents
furnishes isomeric mixtures of the corresponding biaryls. In
light of these investigations, we developed a simple, selective
and efficient method for the formation of biaryls starting with
simple commercially available compounds. Also we showed
that MnIII acetate is more selective and effective than CoIII,
CeIV and PbIV. This method offers an attractive alternative to
the other published methods. Coupling of arylhydrazines in
heteroaromatic solvents is under investigation.
Experimental
NMR spectra were recorded on a Bruker DPX 400. Column
chromatography was conducted on silica gel 60 (mesh size 40–
63 µm). TLC was carried out on aluminium sheets precoated
with silica gel 60F254 (Merck), and the spots were visualized
with UV light (λ = 254 nm). IR spectra were measured on a
Philips model PU9700 spectrometer. GC-MS spectra were
determined using a ThermoQuest (TSP) TraceGC-2000 Series
equipped with phenomenex Zebron ZB-5 capillary column (5%
phenylmethylsiloxane, 30 m, 250 µm; T GC(injector) = 250 ЊC,
T MS(ion source) = 200 ЊC, time programme (oven): T 0
=
min
60 ЊC, T 3 min = 60 ЊC, T 14 min = 280 ЊC (heating rate 20 ЊC minϪ1),
T 20 = 280 ЊC, MS: ThermoQuest Finnigan multi Mass (EI,
min
The results in Tables 1 and 3 show that oxidation of phenyl-
hydrazine with oxidants showing similar behavior towards a
70 eV). Mps were measured on a capillary tube apparatus and
are uncorrected.
J. Chem. Soc., Perkin Trans. 1, 2001, 3042–3045
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Table 1 The synthesis of biaryls
1
2a
Yield (%)b
75
Mp (lit.)
a
b
69 (69–72c)
70
73
Oil
Oil
c
d
e
81
69
91–92 (90–92c)
60–62 (59–6114a
)
f
80
49–50 (49–5014b
)
g
h
83
68
89 (86–90c)
37–39 (36–38c)
i
j
75
74
Oil
112 (111–11214c
)
k
69
Oil
a All products were identified by spectroscopic methods (NMR, IR, GC-MS) and the data were in agreement with the published values.14 If
necessary, additional purification was done by column chromatography (silica gel; 5% diethyl ether–hexane). b The yields indicate the loss of some
material at some stage of the reaction. Loss of product during work-up or adsorption of starting material by salts during reaction might be the
reason. This problem is still under investigation. c Commercially available material.
Table 2 Ratio of isomers obtained in the oxidation of hydrazines
was refluxed for 4 hours. After completion of the reaction, the
mixture was filtered off and the residue was washed with 15 ml
of Et2O. The resulting solution was washed successively with
saturated aq. NaHCO3, NH4Cl, and brine, and dried over
MgSO4. Concentration under reduced pressure furnished 0.4 g
of biphenyl (mp 71–73 ЊC), confirmed by NMR, IR and
GC-MS as the sole product. Reactions with CoIII, CeIV and
PbIV were run in basically the same fashion with a 1 : 2 phenyl-
hydrazine to oxidant mole ratio.
Proportions of isomers
Hydrazine
Solvent
o-
p-
m-a
1a
1a
1b
1f
1g
1h
Bromobenzene
Toluene
Bromobenzene
Toluene
Bromobenzene
Toluene
47.7 : 29.5 : 22.7
70.4 : 21.1 : 8.4
38.2 : 33.7 : 28.0
50.5 : 26.2 : 23.2
60.1 : 29.6 : 10.3
61.2 : 21.4 : 17.3
Acknowledgements
a Positions are based on the solvent used and are determined from the
crude products by GC-MS using commercially available products as
references.
Financial support by the Middle East Technical University
(AFP-2000), the Turkish Scientific and Technical Research
Council (TUBITAK) and the Turkish State Planning Organ-
isation DPT is gratefully acknowledged.
Typical procedure
A mixture of manganese() acetate [2.79 g, 10.4 mmol
Mn(OAc)3ؒ2H2O] in 30 ml benzene was refluxed for 30 minutes
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Table 3 Oxidation products of phenylhydrazine with various oxidants
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