Synthesis, structure, and properties of benzoquinone dimer and trimers bearing t-Bu substituents

Article abstract of DOI:10.1021/ol702289u

Highly soluble and stable quinone dimer and trimers were successfully yielded by introduction of t-Bu substituents. In X-ray structure analysis, the dimer quinone moiety was distorted into the boat shape, which was clarified by MO calculations. X-ray and

Full text of DOI:10.1021/ol702289u

ORGANIC
LETTERS
2
007
Vol. 9, No. 26
417-5420
Synthesis, Structure, and Properties of
Benzoquinone Dimer and Trimers
Bearing t-Bu Substituents
5
,
†
†
†
†
Naoto Hayashi,* Takahiro Yoshikawa, Takahiro Ohnuma, Hiroyuki Higuchi,
,
‡
,§
Katsuya Sako,* and Hidehiro Uekusa*
Graduate School of Science and Engineering, UniVersity of Toyama, Gofuku, Toyama
9308555, Japan, Department of Life and Materials Engineering, Nagoya Institute of
Technology, Gokiso, Nagoya 4668555, Japan, and Department of Chemistry and
Materials Science, Tokyo Institute of Technology, Ookayama, Tokyo 1528551, Japan
nhayashi@sci.u-toyama.ac.jp; sako@mail.manage.nitech.ac.jp; uekusa@cms.titech.ac.jp
Received September 20, 2007
ABSTRACT
Highly soluble and stable quinone dimer and trimers were successfully yielded by introduction of t-Bu substituents. In X-ray structure analysis,
the dimer quinone moiety was distorted into the boat shape, which was clarified by MO calculations. X-ray and UV/vis studies indicated that
the covalently linked quinone moieties bear a large torsional angle. Nevertheless, the reduction potentials rose significantly with the order of
monomer < dimer < trimer, indicating that the negative charge was efficiently delocalized within the radical anions.
1
4
Benzoquinone, or quinone, is abundant in chemistry. In
attention because of its anti-HIV activities. In addition,
5
biological sciences, it constitutes part of the structure of
ubiquinone (coenzyme Q), which acts as a lipid-soluble
electron carrier in the membrane-bound respiratory chain.
Quinone is also employed as an electron-acceptor moiety in
photoinduced electron transfer (PIET) in (artificial) photo-
humic acid contains a mixture of quinone oligomers.
2
Nevertheless, only a few quinone oligomers are reported,6
and even the quinone dimer has yet to be fully characterized.
This may be due to their poor solubility, since nonsubstituted
quinone dimers and trimers are reported to be sparingly
3
5a
synthesis. The strong electron-acceptor character of quinone
soluble in common organic solvents. Moreover, they are
plays an important role in these systems. The radical anion
state is stabilized by delocalization of the negative charge
in linked quinone derivatives (i.e., quinone oligomers), thus
acceptor ability is likely to increase significantly in quinone
oligomer systems. In relation to this, conocurvone is a natural
compound bearing quinone moieties. It is comprised of three
covalently linked naphthoquinones, and has attracted much
so unstable that they decompose gradually when recrystal-
lized from ethanol. In this report, we have presented the
design, synthesis, structural and electrochemical properties,
(
4) (a) Yin, J.; Liebeskind, L. S. J. Org. Chem. 1998, 63, 5726. (b) Emadi,
A.; Harwood, J. S.; Kohanim. S.; Stagliano, K. W. Org. Lett. 2002, 4, 521.
5) (a) Erdtman, H.; Granath, M.; Schultz, G. Acta Chem. Scand. 1954,
(
8
, 1442. (b) Madkour, T. M. Polym. J. 1997, 29, 670.
(6) (a) Lounasmaa, M. Acta Chem. Scand. 1965, 19, 540. (b) Laatsch,
H. Liebigs Ann. Chem. 1990, 433. (c) Liebeskind, L. S.; Riesinger, S. W.
Tetrahedron Lett. 1991, 32, 5681. (d) Yin, J.; Liebeskind, L. S. J. Org.
Chem. 1998, 63, 5726. (e) Buck, R. P.; Wagoner, D. E. J. Electroanal.
Chem. 1980, 115, 89. (f) Czuchajowski, L.; Duraj, S.; Kucharska, M. J.
Mol. Struct. 1976, 34, 187. (g) Buchan, R.; Musgrave, O. C. J. Chem. Soc.,
Perkin Trans. 1 1975, 2185. (h) Hayashi, N.; Yoshikawa, T.; Kurakawa,
M.; Ohnuma, T.; Sugiyama, Y.; Higuchi, H. Mol. Cryst. Liq. Cryst. 2006,
456, 133. (i) Anderson, J. C.; Denton, R. M.; Wilson, C. Org. Lett. 2005,
7, 123.
†
University of Toyama.
Nagoya Institute of Technology.
Tokyo Institute of Technology.
‡
§
(1) The Chemistry of the Quinonoid Compounds; Patai, S., Rappoport,
Z., Eds.; Wiley: Chichester, UK, 1988.
(
(
2) Ernster, L.; Dallner, G. Biochim. Biophys. Acta 1995, 1271, 195.
3) Wasielewski, M. R. Chem. ReV. 1992, 92, 435.
1
0.1021/ol702289u CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/21/2007

and acceptor characteristics of quinone dimer and trimer
derivatives. Furthermore, we have reported that quinone
7
p
m
dimer (QQ) and trimers (QQ Q and QQ Q) can be easily
handled by the introduction of t-Bu groups.
p
m
QQ, QQ Q, and QQ Q were synthesized as shown in
Scheme 1. 2-Bromo-5-tert-butyl-1,4-dimethoxybenzene (1)
p
m
Scheme 1. Synthesis of QQ, QQ Q, and QQ Q
Figure 1. X-ray structure of (a) Q and (b) QQ.
molecules were centrosymmetric, situated on the inversion
center of the crystal. The structural parameters of the quinone
moiety (bond lengths, bond angles, and dihedral angles) were
virtually identical with those of nonsubstituted benzoquinone,
except for the length of bond C1-C2, which increased by
0
.024 Å, This was probably due to steric repulsion between
the t-Bu group and the oxygen atom (see the Supporting
Information).
QQ yielded good crystals suitable for X-ray diffraction
studies by slow evaporation of 1,2-dimethoxyethane (DME)
solution. The X-ray structure of QQ (Figure 1b) displayed
2
-fold symmetry, where the 2-fold axis was perpendicular
to the quinone-quinone (C2-C2′) bond. Two quinone
moieties in QQ were twisted with φ (the dihedral angle of
C3-C2-C2′-C3′) of 37.7(3)°, which is somewhat smaller
was converted to boronic acid 2, then subject to Suzuki-
Miyaura coupling with 1 to obtain the dimethoxybenzene
than those values typically found in biphenyl derivatives
8
9
(
40-50°). Notably, the quinone ring was in the boat form
dimer 3. The dimer was oxidized by cerium ammonium
as opposed to planar. Two carbon-carbon double bonds
C2dC3 and C5dC6) lay approximately on the same plane,
p
nitrite (CAN) to afford QQ in good yield. Similarly, QQ Q
(
was synthesized from 2,5-dibromo-1,4-dimethoxybenzene 4
with both carbonyl groups (C1dO1 and C4dO2) situated
on the same side. The largest deviation from the least-squares
plane was found for O1, with an atom-plane distance of
m
via dimethoxybenzene trimers 5, and QQ Q from 2,6-
dibromo-1,4-dimethoxybenzene 6 via 7. Owing to the t-Bu
substituent, QQ was highly soluble in various organic
solvents such as benzene, chloroform, ether, ethanol, and
ethyl acetate, and moderately so in hexane. On the other
0
.44 Å. The bond lengths and bond angles of QQ were
almost identical with those of Q, despite the boat formation.
The bond connecting the two quinone moieties (C2-C2′ )
p
m
hand, solubility was somewhat lower for QQ Q and QQ Q.
In contrast with nonsubstituted quinone oligomers, none of
the oligomers in this study underwent decomposition for at
least several days when kept in the dark.
1
.482(3) Å) was found to be 0.02 Å shorter than the
corresponding bond of the naphthoquinone dimer (1.504(5)
10
Å). This was attributed to the partial double bond character
of the former, in contrast with the latter, which should
virtually be regarded as a single bond. In the former, p
orbitals of C2 and C2′ overlap considerably, whereas in the
latter, the two quinone moieties form almost a right angle.11
X-ray analysis of 2,5-tert-butyl-1,4-benzoquinone (Q) was
performed for comparison. As shown in Figure 1a, the
(7) Although QQ is a known compound (Hewgill, F. R.; Hewitt, D. G.
J. Chem. Soc., Sect. C 1967, 723.), its redox behavior and precise molecular
structure was not investigated.
(9) Berresheim, A. J.; M u¨ ller, M.; M u¨ llen, K. Chem. ReV. 1999, 99, 1747.
(10) Lumb, J.-P.; Trauner, D. Org. Lett. 2005, 7, 5865.
(8) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
5418
Org. Lett., Vol. 9, No. 26, 2007

Evidently, the boat formation of QQ should not be
attributed to the t-Bu substituent, since the quinone ring of
Q was not distorted (Figure 1a). Detailed examination of
the X-ray structure of QQ revealed short intramolecular
contact between the oxygen atoms (O1 and O1′), with an
interatomic distance of 2.912(3) Å. This is considerably
smaller than the sum of van der Waals radii of two oxygen
robiphenyl (ClBP). The energy differences of QQ′ were even
smaller than the corresponding ones of ClBP, and were
similar to those of FBP. This was probably due to differences
in their van der Waals radii (F, 1.47 Å; O, 1.52 Å; Cl, 1.75
1
2
Å) and covalent bond lengths (C-F, 1.34 Å; CdO, 1.21
Å; C-Cl, 1.73 Å). QQ′ has two energy minima at 62° and
135°. Double energy minima were also seen in FBP (57°
and 129°), while ClBP had only one energy minimum (90°).
It is noteworthy that, in comparison of the energy minima
of QQ′, E62° (syn conformer) is lower than E135° (anti
1
2
atoms (3.04 Å), and thus can be deemed responsible for
the distortion. The short contact between the oxygen atoms
may simply be attributed to packing demand. However, to
investigate other factors, MO calculations were performed
at the B3LYP/6-311+G(d,p) and HF/6-31G(d) levels. The
former method was applied to obtain the optimized geometry
of syn and anti conformers of the unsubstituted quinone
dimer (QQ′) as a model compound. The quinone moiety was
essentially planar and φ was found to be 137.1° in the
optimized anti conformer. Conversely the boat-shaped quino-
ne was reproduced in the syn conformer (φ was fixed at 37.7°
based on the X-ray structure), where the oxygen-oxygen
-
1
conformer) by 1.48 kcal mol . A preference for the syn
conformer was found via MO calculations, as well as in
electron diffraction studies of FBP and ClBP. This suggested
the existence of a particular interaction between the halogen
atoms. Similarly, this result implies that an oxygen-oxygen
interaction may well exist in the quinone dimer, which may
have been responsible for the syn conformation found in
X-ray structure analysis of QQ. The presence of an oxygen-
oxygen interaction was also supported by the result of the
B3LYP/6-311+G(d,p) calculation. Despite the short contact
between oxygen atoms and the distortion of the quinone
moiety, the energetic disadvantage of the syn conformer was
unexpectedly small. Conclusively, the boat shape observed
in the X-ray crystal of QQ must have been due to the short
contact between the adjacent oxygen atoms, which probably
arose from the packing demand, and/or plausible oxygen-
oxygen interaction. Although it was anticipated that X-ray
-
1
distance was 2.93 Å. It was noted that, at 1.07 kcal mol ,
the energy difference was rather small, despite the large
distortion observed in the syn conformer. This result, and
the fact that distortion of the quinone ring into a boat shape
10
is also observed in the naphthoquinone dimer, may indicate
that the quinone ring substituted by a quinone moiety is
considerably prone to distortion.
On the other hand, an HF/6-31G(d) calculation was used
to estimate the rotational barrier of QQ′, where φ was varied
between 0° (coplanar cis), 45°, 90°, 135°, and 180° (coplanar
trans). It is recognized as difficult to accurately reproduce
the experimental data of biaryl rotational barriers by MO
p
m
analysis of QQ Q and QQ Q would give further information
p
m
on this issue, good QQ Q and QQ Q crystals were not
obtained, despite our best efforts.
Electronic absorption spectra (1,4-dioxane) of Q, QQ,
1
3
p
m
methods. Nevertheless, this method was used, as it was
considered worthwhile to obtain a comparison of results by
identical calculation methods. The energy differences found
QQ Q, and QQ Q are shown in Figure 2. When the number
Table 1. Energy Differences (E
and ClBP at Dihedral Angles φ of 0°, 45°, 90°, 135°, and 180°,
φ
, in kcal mol-1) for QQ′, FBP,
Relative to the Energy at the Optimal Dihedral Angle φopt
Given at the Bottoma
,
f
QQ′
FBPb
12.64
0.90
1.03
0.31
6.12
ClBPb
0
4
9
1
1
10.49
46.46
9.75
0.00
4.64
22.74
5
0
35
80
0.76
1.28
1.48
4.83
φopt
62.16/134.95
57.13/128.82
89.66
a
HF/6-31G(d) calculation. b Reference 13.
Figure 2. Electronic absorption spectra of Q (dotted), QQ (broken),
QQ Q (dash-dotted), and QQ Q (solid) in 1,4-dioxane.
are shown in Table 1, accompanied by values obtained
previously for 2,2′-difluorobiphenyl (FBP) and 2,2′-dichlo-
p
m
(
11) As seen in the X-ray structure of polymorphs of substituted bipyrrole,
of quinone moieties increased, molar absorption coefficients
(ꢀ) also increased, although wavelengths of maximum
the bond length linking two π moieties is sensitively altered depending on
the dihedral angle: the pyrrole-pyrrole bond length of the anti conformer,
where the dihedral angle φ ) 180°, is 1.4362(17) Å, whereas that of the
syn conformer, where φ ) 40°, is 1.4490(16) Å (Merz, A.; Kronberger, J.;
Dunsch, L.; Neudeck, A.; Petr, A.; Parkanyi, L. Angew. Chem., Int. Ed.
(12) Bondi, A. J. Phys. Chem. 1964, 68, 443.
(13) Grein, F. J. Phys. Chem. A 2002, 106, 3823.
1
999, 38, 1442).
Org. Lett., Vol. 9, No. 26, 2007
5419

1/2, E
1/2, and E
1/2
were observed in
absorption (λmax, π-π* transition) were observed at almost
the same position (ca. 260 nm). On the other hand, a new
absorption band (shoulder) appeared around 300-340 nm
that almost identical E
1
2
3
m
p
QQ Q and QQ Q. It had been expected that due to the
strong electron-withdrawing substituent effect of the quinone
moiety, the positions of substituents would affect the
reduction potentials, as observed in different stabiliy of 2,6-
dinitrophenoxide compared with 2,5-dinitrophenoxide. Very
littel effect of the positions of substituents on E
seen in comparison to 2,6-dichloro-p-benzoquinone (-0.23
V) and 2,5-dichloro-p-benzoquionone (-0.22 V).15
In conclusion, we have obtained quinone dimer (QQ) and
p
m
in QQ, QQ Q, and QQ Q, indicating essential expansion
of π conjugation over the adjacent moieties. In addition, a
bathochromic shift of the absorption edge (n-π* transition)
was seen on chain elongation. As the energy level of the n
orbital probably does not undergo substituent effects, this
may suggest lowering of the LUMO level (π* orbital).
14
red
1
was also
p
m
The redox behaviors of Q, QQ, QQ Q, and QQ Q were
m
p
measured by cyclic voltammetry (Table 2). In DMF solution,
trimers (QQ Q and QQ Q) in high yield, and found them
to be highly soluble and stable due to t-Bu substituents. MO
calculations showed the structural flexibility of QQ, and
indeed X-ray analysis revealed distortion of the quinone
moiety into the boat form. The origin of the distortion was
due to the short contact between adjacent oxygen atoms,
which arose from packing demand, an oxygen-oxygen
interaction, or both. The first reduction potential was
substantially lowered by covalent linkage of the quinone
moieties. Regardless of the different molecular structure, the
p
Table 2. Reduction Potentials for Compounds Q, QQ, QQ Q,
m
a
and QQ Q
compd
E11/2
E21/2
E31/2
E41/2
E5pc
Q
QQ
-1.05 (1e) -2.13(1e)
-0.78 (1e) -1.25(1e) -2.21b
QQ Q -0.59 (1e) -0.97(1e) -1.31(1e) -1.74b
p
-2.28
m
QQ Q -0.59 (1e) -0.97(1e) -1.32(1e) -2.16(1e)
m
p
reduction potentials of QQ Q and QQ Q were found to be
essentially identical. Studies on higher quinone oligomers
(n g 4) and oligomers bearing an appropriate spacer are
currently underway.
a
Electrode: Pt (working), Pt (counter), and Ag/Ag+ (reference). Sup-
porting electrolyte: n-Bu4NClO4. Solvent: DMF. Scan rate: 100 mV/s.
b
pc
Irreversible (thus, Ex is shown).
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Science, Sports, and Culture, Japan (17750035).
Q exhibited two well-defined one-electron reversible redox
waves, corresponding to the formation of a radical anion,
followed by dianion at higher potential. QQ showed three
waves; the first and second ones were reversible correspond-
ing to the formation of a radical anion and dianion,
respectively, whereas the third was irreversible. The first,
second, and third redox waves were reversible both for
Supporting Information Available: Synthetic proce-
p
dures, spectroscopic data for compounds QQ, QQ Q,
m
QQ Q, 2, 3, 5, and 7, and crystallographic data for Q and
QQ (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
p
m
QQ Q and QQ Q; in contrast, the forth and fifth redox
p
waves were irreversible for QQ Q, while the forth redox
p
OL702289U
wave was also reversible for QQ Q. The initial reduction
potentials were raised considerably in the order of monomer,
dimer, and trimer. This indicates that radical anions generated
from the dimer and trimers were stabilized by means of
delocalization of the negative charge. It may be noteworthy
(
14) Consequently, acidity and reactivity toward amines of these
compound were observed to be significantly different. Bron, J.; Simmons,
E. L. J. Phys. Chem. 1976, 80, 185.
(15) Versus SCE, in acetonitrile. Liu, Y.-C.; Zhang, M.-X.; Yang, L.;
Liu, Z.-L. J. Chem. Soc., Perkin Trans. 2 1992, 1919.
5420
Org. Lett., Vol. 9, No. 26, 2007