950
Published on the web September 1, 2012
Facile Synthesis of Quinone Dimer Derivatives Substituted
with Sulfanyl Groups and Their Properties
Akio Kamimura,*1 Tomomi Nokubi,1 Kotaro Nasu,1 Yasuko Takechi,1 Yuriko Ishihara,1 Kazunari Kato,1
Saori Noguchi,1 Masanori Watanabe,2 Masashi Shirai,2 Michinori Sumimoto,3 and Hidemitsu Uno4
1Department of Applied Molecular Bioscience, Graduate School of Medicine,
Yamaguchi University, Ube, Yamaguchi 755-8611
2Ube Laboratory, Ube Industries Ltd., Ube, Yamaguchi 755-8633
3Department of Material Chemistry, Graduate School of Science and Engineering,
Yamaguchi University, Ube, Yamaguchi 755-8611
4Department of Chemistry, Graduate School of Science and Engineering,
Ehime University, Matsuyama, Ehime 790-8577
(Received June 10, 2012; CL-120563; E-mail: ak10@yamaguchi-u.ac.jp)
OMe
OMe
Quinone dimers are readily prepared quantitatively from 2-
O
O
OMe
OMe
OH
OH
RS
sulfanyl-1,4-dimethoxybenzene by oxidative treatment. The oxi-
dative coupling progressed in a highly regioselective manner.
Removal of O-protection and subsequent oxidation gave 5,5¤-
bis(sulfanylquinone) dimer in good yields. Physical properties of
the dimer derivatives are also investigated.
OMe
OMe
NaH, MeI
dry THF
FeCl3
MeOH
RSH
CH2Cl2-CH3NO2
RS
RS
SR
1
2
3
OH
O
RS
RS
OH
BBr3
O
NaIO4
Quinone derivatives are widely abundant among natural
products.1 Quinone and hydroquinone compose an interesting
redox system and their properties are often observed among natural
metabolic systems as well as artificial functional molecules.
Quinone dimers are expected to show many unique physical
properties because of a synergetic effect by combination of the two
quinones.2 However, there have been only a limited number of
reports describing synthesis of quinone dimers because of their
low stability.3 Another reason is that biaryl coupling reaction for
dimer formation is usually limited to transition-metal-catalyzed
reactions. Recently we launched research on a new chemistry of
combination of sulfur and quinones, and found a very short
synthesis of quinone dimers bearing sulfur substituents. In this
report we describe a new regioselective synthesis of 5,5¤-
disulfanyl-2,2¤-bisbenzoquinone dimer derivatives and their
unique physical properties.
Our synthesis started from the conjugate addition of thiol to
quinone (Scheme 1).4 The addition progressed smoothly at room
temperature and 2-sulfanyl-1,4-hydroquinones 1 are obtained in
almost quantitative yields. The two hydroxy groups in compound
1 were protected by treatment with excess NaH and MeI, giving
hydroquinone dimethyl ether 2 in good yields. Exposure of
compound 2 to FeCl3 in CH3NO2-CH2Cl2 resulted in rapid
consumption of compound 2 and desired dimers 3 were obtained
in good yields.5 The results are summarized in Table 1.
The dimerization reaction occurred smoothly. For example,
compound 2a underwent the oxidative dimerization to give 3a in
99% yield (Entry 1). Compound 3a was isolated in a single
isomer, thus the regioselectivity of the coupling reaction was very
high. The NMR spectrum for 3a appeared in a very simple signal
pattern and its highly symmetric structure was expected. The
structure of 3a was confirmed by X-ray crystallographic analysis,
which revealed the dimer structure unambiguously.6,10 The two
hydroquinone dimethyl ether units connected at the para-position
of phenylsulfanyl group and 2,2¤-dimer was exclusively formed. In
the X-ray structure, the torsional angle between the two hydro-
quinone dimethyl ether rings was estimated to be 76° so the two
rings existed in an almost orthogonal conformation. Since FeCl3
CH2Cl2, 0 °C
OH
O
SR
OH
SR
4
5
O
Scheme 1. Synthesis of quinone dimers 5.
Table 1. Preparation of quinone dimers 5
1;
2;
3;
4;
5;
Entry R
Yield/%a Yield/%a Yield/%a Yield/%a Yield/%a
1
2
3
4
5
6
7
Ph
o-BrC6H4
p-BrC6H4
p-t-BuC6H4 1d; 100 2d; 93
m-ClC6H4 1e; 81
1a; 100 2a; 92
1b; 100 2b; 80
1c; 95
3a; 99
3b; 99
4a; 100 5a; 100
4b; 100 5b; 100
2c; 96
3c; 100 4c; 100 5c; 61
3d; 96
3e; 100 4e; 79
3f; 100 4f; 73
4d; 44
5e; 93
5e; 62
5f; 69
5g; 47
2e; 95
2f; 85
p-ClC6H4
n-C8H17
1f; 98
1g; 49
2g; 100 3g; 84
4g; 62
aIsolated yield.
did not remove methyl ether groups, no further oxidation to 5 was
observed. No oxidation on the sulfanyl group was observed. Other
compounds 2 derived from arylsulfanyl group also gave dimer 3 in
quantitative yields (Entries 2-6). The regioselectivity was equally
high and only a single isomer of dimer 3 was formed. Compounds
2 derived from aliphatic thiols also underwent the dimerization to
give 3 in good yield (Entry 7). Thus, the present oxidative
conditions provided a useful preparation of dimer 3 in good yields.
The present reaction achieved the formation of biaryl derivatives
by direct C-H substitution reaction.7 Removal of methyl groups
was carried out by treatment with BBr3 and hydroquinone dimers 4
were obtained in good yields.6 Oxidative treatment of compounds
4 with NaIO4 resulted in the formation of quinone dimers 5.
The origin of the regioselectivity should be explained in this
way (Scheme 2). Treatment of compounds 2 with FeCl3 resulted in
the single electron oxidation to give radical cation A, which has
resonance structures B and C. In these structures, the sulfanyl
group plays important role to stabilize the cation radical so that the
para-position to the sulfanyl group became the most electrophilic.
The cationic form C is attacked by another hydroquinone dimethyl
Chem. Lett. 2012, 41, 950-951
© 2012 The Chemical Society of Japan