Synthesis of bicyclic quinones via 1,4-diacetoxyanthracene

Article abstract of DOI:10.1016/j.tetlet.2006.10.048

1,4-Diacetoxyanthracene is introduced as a convenient intermediate for the syntheses of bicyclic quinones and diquinones.

Full text of DOI:10.1016/j.tetlet.2006.10.048

Tetrahedron Letters 47 (2006) 8901–8903
Synthesis of bicyclic quinones via 1,4-diacetoxyanthracene
*
Grigoriy A. Sereda, Jesse Van Heukelom and Sudha Ramreddy
The University of South Dakota, Department of Chemistry, 414 E.Clark St., Vermillion, SD 57069, United States
Received 21 March 2006; revised 7 October 2006; accepted 10 October 2006
Available online 30 October 2006
Abstract—1,4-Diacetoxyanthracene is introduced as a convenient intermediate for the syntheses of bicyclic quinones and
diquinones.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
benzoquinone, adduct 3 enolizes to 4 in the reaction
mixture, and after extended refluxing (31 h) yields only
the isomerized product 4. This observation has allowed
us to develop a one-pot synthesis of quinone 6 from 2.
Interestingly, the influence of the diene–dienophile ratio
on the synthetic outcome of this reaction is well repro-
ducible, but its reason remains unclear. Refluxing of
adduct 3 in chlorobenzene alone does not cause the
isomerization, which is probably catalyzed by a side
product of addition to benzoquinone. This control
experiment does not rule out the possibility that the
interaction of the second equivalent of benzoquinone
with 3 retards its enolization. However, such an interac-
tion cannot be considered as the only reason of the sup-
pressing effect of benzoquinone on the enolization of 3.
Deacetylation and subsequent isomerization of adduct 3
in refluxing methanol with a catalytic amount of HCl led
to known 1,4,5,8-tetrahydroxytriptycene 5 (Scheme 1).
Along with the NMR-data, this reaction has provided
an additional structural proof for the diastereomeric
mixture 3. Silver oxide in acetone oxidizes phenolic com-
Bicyclic quinones and diquinones are attracting chem-
ists’ attention as building blocks for organic synthesis,
particularly for molecules, mimicking intramolecular
photoelectron transfer. Recently a series of triptoqui-
nones and triptodiquinones have shown a wide spec-
trum of biological activity such as anti-inflammatory,
1
2
3
4
antimalaria activity, and cytotoxicity against daunoru-
bicin resistant leukemia cell lines.4 Triptodiquinones
have been available through the Diels–Alder addition
of an appropriately substituted benzoquinone to 1,4-
dimethoxyanthracene, followed by a sequence of chem-
1
–4
ical transformations of the adduct.
preparation of 1,4-dimethoxyanthracene involves the
use of dangerous sodium hydride, and according to
our experiments, the final step of oxidative dimethyla-
tion with cerium ammonium nitrate (CAN) is difficult
to reproduce. Although electrochemical and biological
properties of the unsubstituted triptodiquinone 1 are
described in the literature, the compound itself and its
precursor 5 have never been properly characterized.
Neither NMR-spectra nor other supplementary data
for these compounds are available.
However, the
4
4
5
6
5
pound 5 to triptodiquinone 1 as described.
The oxidation of 4 with silver oxide yielded another
bicyclic quinone 6, whose structure was confirmed by
NMR and elemental analysis.
We describe a convenient synthesis of 1, starting from
1
,4-diacetoxyanthracene 2, synthesized by a known pro-
7
cedure. Refluxing of 2 with 2 equiv of 1,4-benzoqui-
none in chlorobenzene readily produces adduct 3 (with
no impurities of 4), which partially isomerizes to hydro-
quinone 4 during purification on silica gel. Interestingly,
if the cycloaddition is performed with only 1 equiv of
In a separate experiment, the conversion of 1,4-di-
acetoxyanthracene 2 to quinone 6 was performed in an
overall yield of 86% without the separation of the
intermediate hydroquinone 4, which gave us a practi-
cally efficient procedure for the synthesis of 6.
A similar approach was applied to synthesize another
bicyclic quinone 8, bearing two carbomethoxy-function-
alities (Scheme 2). The first step of Diels–Alder addition
*
Corresponding author. Tel.: +1 605 677 6190; fax: +1 605 677
397; e-mail: gsereda@usd.edu
6
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.10.048

8902
G. A. Sereda et al. / Tetrahedron Letters 47 (2006) 8901–8903
OCOCH
3
OH
O
1,4-Benzoquinone,
H CC(O)O
H3CC(O)O
1
,4-Benzoquinone,
equiv.
PhCl, reflux, 4 h
3
1
equiv.
2
4
+
PhCl, reflux,
1 h
9
0%
3
OH
O
OCOCH
O(O)CCH
O(O)CCH3
3
3
Ag O,
2
4, 13%
2
3, 65%
acetone,
reflux, 1.5 h
O
O
O
CH OH, HCl,
3
H CC(O)O
3
reflux, 3 h
O
Ag O,
acetone,
2
O
O
O(O)CCH
3
OH
reflux, 3 h
6, 86%
1, 89%
HO
OH
OH
5, 91%
Scheme 1.
O
H
H
H
H
O
O
COOCH
3
H
H
COOCH
3
COOCH
3
O
Maleic anhydride,
PhCl, reflux
H CC(O)O
3
COOCH3
HO
CH OH, HCl
Ag2O
3
2
O
O(O)CCH
3
OH
10, 81%
8, 55%
9, 94%
Scheme 2.
selectively proceeded in the anti-fashion. The structure
of adduct 9 was confirmed by the X-ray analysis of
the final quinone 8.
Grant 0532242 for the purchase of an Elemental Ana-
lyzer used in this research and South Dakota EPSCoR
stipend for Jesse Van Heukelom) for the financial
support of this work. We are thankful to Dr. Andrew
Sykes for X-ray analysis of quinone 8.
The observed stereochemistry of addition of maleic
anhydride to 2 formally contradicts the rule of ‘accumu-
lation of multiple bonds’ and can be explained by the
opposite orientations of the dipole moments of
Supplementary data
1
,4-diacetoxyanthracene and maleic anhydride at the
moment of Diels–Alder addition.
1
Experimental procedures and H NMR spectra for all
synthesized compounds, elemental analysis for
compound 3, and the X-ray data for compound 8.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
In summary, we introduced a simple addition–deprotec-
tion–oxidation sequence of chemical transformations
that provides an easy access to a variety of practically
useful bicyclic quinones and diquinones.
2
006.10.048.
Acknowledgments
References and notes
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We thank the State of South Dakota (2010 Research ini-
tiative and the Governor’s 2010 Individual Research
Seed Grant Award), the University of South Dakota
1
2. Wiehe, A.; Senge, M. O.; Kurreck, H. Liebigs Ann. 1997,
(
the Nelson research grant) and the NSF (NSF URC
1951–1963.

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