Manganese(III) acetate-mediated oxidative coupling of phenylhydrazines with furan and thiophene: A novel method for hetero biaryl coupling

Article abstract of DOI:10.1016/S0040-4020(02)01001-3

A convenient new method for the arylation of furan and thiophene with arylhydrazine and manganese(III) acetate is described. Oxidation of arylhydrazines with Mn(III) acetate in furan or thiophene affords the corresponding 2-aryl-substituted furans and thiophenes in good yield using commercially available materials; access to 2-substituted heterobiaryls works selectively, and coupling occurs with loss of the hydrazine moiety.

Full text of DOI:10.1016/S0040-4020(02)01001-3

Tetrahedron 58 (2002) 8055–8058
Manganese(III) acetate-mediated oxidative coupling of
phenylhydrazines with furan and thiophene:
a novel method for hetero biaryl coupling
¨
Ayhan S. Demir, Omer Reis and Mustafa Emrullahoglu
*
˘
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 18 May 2002; revised 22 July 2002; accepted 15 August 2002
Abstract—A convenient new method for the arylation of furan and thiophene with arylhydrazine and manganese(III) acetate is described.
Oxidation of arylhydrazines with Mn(III) acetate in furan or thiophene affords the corresponding 2-aryl-substituted furans and thiophenes in
good yield using commercially available materials; access to 2-substituted heterobiaryls works selectively, and coupling occurs with loss of
the hydrazine moiety. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
3-substituted heterocycles just by using the appropriately
substituted coupling partners.
Aryl-substituted aromatic heterocycles are interesting
compounds as precursors to biologically and physiologi-
cally active compounds. They also exist in naturally
occurring compounds such as pterofuran,1 2-phenyl-5-
propynylthiophene,2 and 3,4,5-tribromo-2-(3,5-dibromo-2-
hydroxyphenyl)pyrrole.3 Usually arylfurans, thiophenes and
C-arylpyrroles are prepared by ring synthesis. Pd(II) salts
are known to dimerize arenes4 and aromatic heterocycles
such as furans,5a,b thiophenes,5b,c and N-benzoyl pyrroles.6
This Pd(II) salt methodology has been applied to the
oxidative cross-coupling of aromatic heterocycles and
arenes that employ stoichiometric amounts of Pd(OAc)2 in
the presence of excess arene in acetic acid solution.7 It has
been shown that the conditions applied furnished both 2-
and 3-aryl-substituted aromatic heterocycles as well as other
side products. Another method utilizes Rh(I) or Ag(I)
catalysts, in which allenyl ketones can be selectively
rearranged into furans under mild conditions. This very
useful method yields 2-arylfurans when aryl ketones are
used.8 Catalytic-coupling reactions are now the routine
means of access to biaryls. In these catalytic-coupling
methods, the course of the reaction is determined by the
position of the functional group specific to the method
employed so that regioselective coupling is possible.9a
There are some studies utilizing these catalytic-coupling
reactions for the synthesis of aryl-substituted furans and
thiophenes.9b–d These methods allow the synthesis of 2- or
Another method is the decomposition of arenediazonium
salts in a large excess of furans or thiophenes, which
furnishes 2-aryl-substituted furans and thiophenes, respec-
tively.10 Methods related to the decomposition of arenedi-
azonium salts involve the generation of aryl radicals in the
presence of furans or thiophenes. It has been shown that the
reaction of derivatives of diazoaminobenzene and isoamyl
nitrite in solvent furan affords 2-aryl furans in 30–50%
yield.11 Irradiation (in benzene solution) of 5-iodo and 5-
bromo-thiophene(furan)-2-carbaldehyde or the correspond-
ing methyl ketones furnishes the corresponding 5-phenyl
derivatives in very good yields.12
The generation of aryl radicals and the formation of biaryls
from arylhydrazines by various oxidizing agents have been
reported. The earliest example is the oxidation of phenyl-
hydrazine by mercury(II) oxide in which aniline and
biphenyl are the isolated oxidation products.13 Several
oxidants for the oxidation of arylhydrazines have been
reported so far, such as Pb(IV),14 Pd or Pd–Hg,15 barium
ferrate monohydrate,16 and manganese dioxide.17 All of
these oxidants either gave poor yields of biaryls when used
in the presence of benzene or other side products like
azobenzene or corresponding arenes.
Recently, we showed Mn(III) acetate to be a versatile
reagent for the generation of aryl radicals from arylhydra-
zines and their subsequent capture by solvent benzene for
the synthesis of biaryls substituted from a single phenyl
ring.18 In the same study, we showed that manganese(III)
acetate was the reagent of choice among the oxidants
Keywords: arylcoupling; thiophene; furan; manganese(III) acetate.
*
Corresponding author. Tel.: þ90-312-2103242; fax: þ90-312-2101280;
e-mail: asdemir@metu.edu.tr
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01001-3

8056
A. S. Demir et al. / Tetrahedron 58 (2002) 8055–8058
Table 1. The synthesis of 2-aryl furan and thiophene
1
2
X
Yield
(%)
a
b
c
O
S
60
70
53
65
60
Scheme 1.
bearing similarities, with respect to a given substrate class,
such as the one electron oxidants Co(III) acetylacetonate,
and cerium(IV) ammonium nitrate. Reactions with man-
ganese(III) acetate not only gave high yields (68–83%), but
also were advantageous in terms of product isolation
(Scheme 1).
O
S
d
e
O
In light of these observations, we applied this reaction to the
synthesis of aryl-substituted heterocycles. Herein, we report
the formation of 2-arylfurans and 2-arylthiophenes via
oxidation of arylhydrazines by manganese(III) acetate
(Scheme 2).
f
S
68
65
g
O
h
i
S
O
S
54
64
52
2. Result and discussion
j
In our previous report, we showed that the oxidation of
arylhydrazines is applicable to both free arylhydrazines and
their salts without any complication. First, we examined the
oxidation of phenylhydrazine and its salt by manganese(III)
acetate in furan or thiophene. The reaction of free
phenylhydrazine was sluggish and furnished a complex
mixture of products as well as the desired 2-phenyl furan 2a.
However, phenylhydrazinium chloride 1a smoothly
afforded the desired products 2a and 2b both in furan and
thiophene as shown in Table 1. This observation is
advantageous since most commercially available arylhydra-
zines are available as their HCl salts. Moreover, free
hydrazines can easily be converted into their salts by
passing dry HCl through their ether solutions. Another
issue, apart from the optimum reaction conditions, is the
regioselectivity of the reaction. Analysis of samples taken
from the reaction mixture by GC–MS always showed the
presence of one isomer, identified as 2-substituted furan or
thiophene by NMR spectroscopy. This was expected since it
is known that a reaction at the 3-position of furan or
thiophene is not easy to achieve and frontier orbitals favor
this type of reactivity.19
k
l
O
S
30
62
m
n
O
S
22
60
All products were identified by spectroscopic methods (NMR, IR, GC–
MS) and data were in agreement with the published values.20
previous work related to the synthesis of biaryls under the
same reaction conditions. Moreover, products are easily
purified just by filtration of the crude mixture through a pad
of silica using hexane or petroleum ether as eluent. This
method afforded analytically pure heterobiaryls in most
cases. The results are summarized in Table 1.
In the oxidation of monoarylhydrazines with several
oxidizing agents, the observed products have been
explained in terms of generated phenyldiimide and its
subsequent breakdown. A mechanism similar to that
proposed for lead(IV) acetate and Cu(II) is probably in
effect during the reaction, which is outlined in Scheme 3.14,21
This radical mechanism is also consistent with our previous
results in which the use of substituted benzenes as solvent
furnished an isomeric mixture without an apparent selectiv-
ity, characteristic of reactions of radicals with substituted
After examination of the formation of 2-phenylfuran and 2-
phenylthiopene from phenylhydrazinium chloride, other
commercially available hydrazines 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 gave the
corresponding 2-substituted furan or thiophene without
isomerization as observed by GC–MS and NMR spectro-
scopy, and this observation was in agreement with our
Scheme 3.
Scheme 2.

A. S. Demir et al. / Tetrahedron 58 (2002) 8055–8058
8057
benzenes. Theoretically 2 equiv. of manganese (III) acetate
are needed for oxidation but the best results are obtained
using 3 equiv. of manganese(III) acetate. This is in
agreement with our previous work with this oxidant where
excess oxidant was sometimes necessary for better yields.22
There are two possible reasons for this observation. First,
the third equivalent of the oxidant is necessary to oxidize the
intermediate radical formed by attack of the aryl radical on
furan or thiophene. Second, since Mn(III) acetate is a
hydrate of unspecified composition and forms manganese
oxide hydrate with water,22d the exact content of the Mn(III)
is uncertain. The manganese(III) acetate used in this study
was commercial and dried over P2O5 prior to use.
Alternatively it can be synthesized from manganese(II)
nitrate and acetic anhydride.22a
7.02 (td, J¼7.6, 1.6 Hz, 1H), 7.08 (dd, J¼3.4, 0.7 Hz, 1H),
7.38 (td, J¼7.7, 1.3 Hz, 1H), 7.42 (dd, J¼1.8, 0.8 Hz, 1H),
7.56 (dd, J¼7.9, 1.7 Hz, 1H), 7.72 (dd, J¼7.9, 1.1 Hz, 1H);
13C NMR (100 MHz, CDCl3): d 110.9, 111.7, 120.0, 127.6,
128.6, 129.1, 131.6, 134.4, 142.3, 151.6. Anal. calcd for
C10H7BrO (223.07): C, 53.84; H, 3.16; found: C, 53.71; H,
3.38.
3.1.2. 2-(2-Bromophenyl)-thiophene (2d). Yield 65%,
colorless oil, data consistent with the literature.20c
3.1.3. 2-(3-Bromophenyl)-furan (2e). Yield 60%, colorless
oil, data consistent with the literature.8
3.1.4. 2-(3-Bromophenyl)-thiophene (2f). Yield 68%, color-
lessoil, nmax(neat)2923, 1610, 1586, 1490, 800,730 cm21;1H
NMR (400 MHz, CDCl3): d 6.97 (m, 1H), 7.11–7.20 (m, 3H),
7.28 (m, 1H), 7.42 (m, 1H), 7.65 (s, 1H); 13C NMR (100 MHz,
CDCl3): d 123.4, 124.1, 124.8, 125.3, 125.8, 128.3, 129.2,
130.6, 136.8, 143.0. Anal. calcd for C10H7BrS (239.13): C,
50.23; H, 2.95; found: C, 50.41; H, 3.12.
In conclusion, we have shown that it is possible to oxidize
arylhydrazines with Mn(III) acetate in furan or thiophene to
form the corresponding 2-aryl-substituted furans and
thiophenes in good yield with commercially available
materials; access to 2-substituted heterobiaryls works
selectively, and coupling occurs with loss of the hydra-
zine. This method is a useful alternative to the published
methods.
3.1.5. 2-(4-Bromophenyl)-furan (2g). Yield 65%, white
crystals, mp 80–828C (lit.,20d 80–838C), data consistent
with the literature.
3.1.6. 2-(4-Bromophenyl)-thiophene (2h). Yield 54%,
white crystals, mp 100–1018C (lit.,20e 1008C), data
consistent with the literature.
3. Experimental
NMR spectra were recorded on a Bruker DPX 400
spectrometer. Chemical shifts d are reported in ppm relative
to CHCl3 (1H: d¼7.26) and CDCl3 (13C: d¼77.0) as internal
standard. Column chromatography was conducted on silica
gel 60 (mesh size 40–63 mm). TLC was carried out on
aluminum sheets precoated with silica gel 60F254 (Merck),
and the spots were visualized with UV light (l¼254 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% phenyl-
methylsiloxane, 30 m, 250 mm; TGC(injector)¼2508C,
TMS(ion source)¼2008C, time program (oven):
T0 min¼608C, T3 min¼608C, T14 min¼2808C (heating rate
208C min21), T19 min¼2808C, T25 min¼2808C, MS: Thermo
Quest Finnigan multi Mass (EI, 70 eV). Mps were measured
on a capillary tube apparatus and are uncorrected.
3.1.7. 2-(3,4-dichlorophenyl)-furan (2i). Yield 64%, white
crystals, mp 51–528C (lit.,11 51–528C); nmax(KBr) 2920,
1
1596, 1575, 1496, 1013, 885 cm21; H NMR (400 MHz,
CDCl3): d 6.33 (m, 1H), 6.51 (m, 1H), 7.29–7.33 (m, 3H),
7.61 (m, 1H); 13C NMR (100 MHz, CDCl3): d 106.6, 112.2,
123.2, 125.9, 130.9, 131.0, 131.4, 133.4, 143.0, 152.0. Anal.
calcd for C10H6Cl2O (213.06): C, 56.37; H, 2.84; found: C,
56.21; H, 2.98.
3.1.8. 2-(3,4-dichlorophenyl)-thiophene (2j). Yield 52%,
white crystals, mp 61–628C; nmax(KBr) 3104, 2925, 1468,
1132, 1025, 857, 826, 714, 536 cm21; 1H NMR (400 MHz,
CDCl3): d 7.0 (dd, J¼6.9, 3.7 Hz, 1H), 7.20 (dd, J¼3.6,
0.9 Hz, 1H), 7.23 (dd, J¼5.1, 0.9 Hz, 1H), 7.35 (m, 2H),
7.60 (d, J¼1.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): d
124.4, 125.3, 126.1, 127.9, 128.5, 131.0, 131.7, 133.5,
134.8, 142.0. Anal. calcd for C10H6Cl2S (229.13): C, 52.42;
H, 2.64; found: C, 52.25; H, 2.88.
3.1. Typical procedure
To a mixture of manganese(III) acetate (563 mg, 2.1 mmol
Mn(OAc)3·2H2O) in 10 mL furan or thiophene, phenyl-
hydraziniumchloride (100 mg, 0.7 mmol) was added and the
resulting mixture refluxed for 5–10 h (formation of the
products was monitored by TLC using n-hexane/silica gel).
After completion of the reaction, the mixture was filtrated
through a pad of silica using hexane or petroleum ether as
eluent. Concentration under reduced pressure furnished 2-
phenylfuran (2a) (50 mg, 60%, colorless oil, (lit.20a) and 2-
phenylthiophene (2b) (77 mg, 70%, mp 35–368C (lit.,20b 34–
368C, whitecrystals), asconfirmedbyNMR,IR, andGC–MS.
3.1.9. 2-(4-Methoxyphenyl)-furan (2k). Yield 30%, white
crystals, mp 36–378C (lit.,20a 37–388C), data consistent
with the literature.
3.1.10. 2-(4-Methoxyphenyl)-thiophene (2l). Yield 62%,
white crystals, mp 105–1078C (lit.,9d 106–1078C), data
consistent with the literature.
3.1.11. 2-(Pentafluorophenyl)-furan (2m). Yield 22%,
white crystals, mp 36–378C (lit.,20f 37–388C), data
consistent with the literature.
3.1.1. 2-(2-Bromophenyl)-furan (2c). Yield 53%, colorless
oil, nmax(neat) 2932, 2855, 1475, 1008, 756, 719 cm21; 1H
NMR (400 MHz, CDCl3): d 6.42 (dd, J¼3.4, 1.9 Hz, 1H),
3.1.12. 2-(Pentafluorophenyl)-thiophene (2n). Yield 60%,
colorless oil, data consistent with the literature.20g

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A. S. Demir et al. / Tetrahedron 58 (2002) 8055–8058
11. Fisera, L.; Kovac, J.; Komanova, E.; Lesko, J. Tetrahedron
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