Benzoannulation of quinones by a cycloaddition-fragmentation approach. A simple synthesis of methoxycarbonyl-substituted polyacenoquinones

Article abstract of DOI:10.1002/jccs.200400025

The cycloadducts 2A-5A obtained from the Diels-Alder cycloadditions of 1,2,3,4-tetrachloro-4,5-dimethoxycyclopentadiene (1) with p-benzoquinone (2), 1,4-naphthoquinone (3), 1,4-anthraquinone (4), and 2,3-dicyano-1,4-benzoquinone (5) were subjected to the reaction with triethylamine in dichloromethane at room temperature. Cycloadducts 2A and 5A enolized to give the corresponding hydroquinones 2B and 5B, which were oxidized with DDQ to afford naphthoquinone ester 2D and anthraquinone ester 5D, respectively. In the cases of cycloadducts 3A and 4A, the enolization occurred concurrently with oxidation and fragmentation to produce directly the polyacenoquinone esters 3D and 4D, respectively. Under the same reaction condition, the unsymmetrical cycloadduct 6A derived from naphthoquinone ester 2D and 1 yielded isomeric polyacenoquinone esters 6Da and 6Db in a ratio of about 8:1.

Full text of DOI:10.1002/jccs.200400025

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Journal of the Chinese Chemical Society, 2004, 51, 167-174
167
Benzoannulation of Quinones by a Cycloaddition-Fragmentation
Approach. A Simple Synthesis of Methoxycarbonyl-Substituted
Polyacenoquinones
Teh-Chang Chou* (
Department of Chemistry and Biochemistry, National Chung Cheng University,
), Chia-Jung Hsu (
) and Jao-Yu Chen (
)
Ming Hsiung, Chia Yi 621, Taiwan, R.O.C.
The cycloadducts 2A-5A obtained from the Diels-Alder cycloadditions of 1,2,3,4-tetrachloro-4,5-di-
methoxycyclopentadiene (1) with p-benzoquinone (2), 1,4-naphthoquinone (3), 1,4-anthraquinone (4), and
2,3-dicyano-1,4-benzoquinone (5) were subjected to the reaction with triethylamine in dichloromethane at
room temperature. Cycloadducts 2A and 5A enolized to give the corresponding hydroquinones 2B and 5B,
which were oxidized with DDQ to afford naphthoquinone ester 2D and anthraquinone ester 5D, respectively.
In the cases of cycloadducts 3A and 4A, the enolization occurred concurrently with oxidation and fragmenta-
tion to produce directly the polyacenoquinone esters 3D and 4D, respectively. Under the same reaction condi-
tion, the unsymmetrical cycloadduct 6A derived from naphthoquinone ester 2D and 1 yielded isomeric
polyacenoquinone esters 6Da and 6Db in a ratio of about 8:1.
Keywords: Benzoannulation; Polyacenoquinones; Diels-Alder reactions; Grob fragmentation.
INTRODUCTION
Ever since its preparation was first reported by New-
alkoxides,6 and could be further facilitated by the electron-
withdrawing substituents at ring-junction carbon atoms and
the eventual aromatization. This intrinsic feature offers addi-
tional application of cycloadducts A to the synthesis of chlo-
rinated aromatic acids and esters.7
comer and McBee in 1949,1 1,2,3,4-tetrachloro-4,5-dimeth-
oxycyclopentadiene (1) has been extensively utilized as a cy-
clic diene in the Diels-Alder cycloadditions with a wide
range of dienophiles.2 This electron deficient cyclic diene 1
reacts successfully with dienophiles having both electron de-
ficient and electron rich groups under mild conditions and
generally provides excellent yields of cycloadducts with a
high degree of stereoselectivity (eq. 1). The Diels-Alder
cycloadducts A thereby formed possess 1,2,3,4-tetrachloro-
7,7-dimethoxybicyclo[2.2.1]heptene ring skeleton and con-
stitute important building blocks for the synthesis of diverse
complex non-natural3 as well as natural products.4 The ring
skeleton contains an electrofugal group (CH3O-C-) and a
nucleofugal atom (-Cl), which are intercalated by a but-2-
en-1,4-diyl (-C-C=C-C-) fragment. This combination creates
a setting for the event of Grob-type fragmentation5 (eq. 2) to
occur that is relayed by the C2-C3 double bond and driven by
the relief of ring strain. The fragmentation would occur much
more readily in the reactions of the corresponding tetrachlo-
roketones, which are derived from the cycloadducts A by
deketalization, and a nucleophile, such as hydroxide and
OCH3
OCH3
Cl
H3CO
Cl
H3CO
Cl
Cl
(1)
(2)
Diels-Alder
cycloaddition
Cl
5
Cl
Cl
Cl
1
A
3
1
H3C
Grob-type
fragmentation
+
O
Cl
H3C
O
Cl
4
2
As part of a current research program that is aimed at
the design and synthesis of photochromic molecules, it was
necessary for us to search for the derivatives of polyacene-
quinones and polyacenes. In this context, we undertook a
study on the accessibility of an approach that was based on a
combination of Diels-Alder cycloaddition and fragmentation
reaction using cyclic diene 1 and quinone dienophiles, as out-
lined in Scheme I. It has been shown that the Diels-Alder
cycloadduct of cyclic diene 1 and dimethyl acetylenedicar-
boxylate undergoes thermal fragmentation to produce tri-
* Corresponding author. Fax: +886-5-2721040; e-mail: chetcc@ccu.edu.tw

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168 J. Chin. Chem. Soc., Vol. 51, No. 1, 2004
Chou et al.
mote enolization and air as the oxidant supplier. The study
was extended to the unsymmetrical cycloadduct 6A, which
was made available from the Diels-Alder cycloaddition of 2D
with cyclic diene 1. The triethylamine-promoted fragmenta-
tion reaction of 6A was found to yield 6Da/6Db directly and
displayed significant regioselectivity. The result is also re-
ported herein.
Scheme I
O
O
O
O
O
O
O
O
CN
CN
O
O
2
3
4
5
Cl
O
OCH3
Cl
H3CO
Cl
Cl
H3CO
2-5
Diels-Alder
cycloaddition
OCH3
RESULTS AND DISCUSSION
Cl
Cl
Cl
Cl
Cl
O
1
Following the established procedure with modifica-
tion,11 the preparation of Diels-Alder cycloadducts of cyclic
diene 1 and the 1,4-quinone dienophiles 2-5 was performed
in toluene at refluxing temperature, and the results are sum-
marized in Table 1. The structures of cycloadducts 2A and 3A
2A-5A
enolization
OH
Cl
H3CO
OCH3
Cl
O
O
Cl
Cl
Cl
OH
1
2B-5B
oxidation
were assured by comparison of H NMR spectral data with
fragmentation
Cl
the reported ones,10 and those of 4A and 5A by the spectral
and elemental analyses. Since the stereochemistry of the
Diels-Alder cycloadducts 2A and 3A has been established to
have endo-configuration in accordance with the Alder-rule
by converting to the corresponding cage compounds using a
photochemical [2+2]cycloaddition,11 the stereochemical out-
come of all cycloadducts 2A-5A prepared in this investiga-
tion is assumed to have endo-configuration as well and was
therefore not determined.12
H3CO
O
2D-5D
Cl
O
OCH3
O
Cl
H3CO
Cl
Cl
2C-5C
methyl 4,5,6-trichlorobenzene-1,2,3-tricarboxylate and chlo-
romethane below the temperature (110 °C) required for its
formation.8 We thus envisioned that once the annulated 1,4-
quinones 2C-5C were formed by the oxidation of hydro-
quinones 2B-5B, they would likely undergo rapid fragmenta-
tion to afford polyacenoquinones 2D-5D. The overall conver-
sion to polyacenoquinone esters shown by Scheme I was first
described by Kniel on the bromination reaction of cyclo-
adduct 3A to yield directly the fragmented anthraquinone es-
ter 3D,9a which could also be obtained by the thermolysis of
3A at 240 °C followed by the oxidation with CrO3.9b More re-
cently Mehta10a and Marchand10b reported that the enolization
of cycloadduct 2A to hydroquinone 2B followed by a
CAN-promoted oxidation of 2B did not furnish the corre-
sponding annulated 1,4-benzoquinone 2C. Instead, fragmen-
tation occurred with concomitant aromatization to afford
naphthoquinone ester 2D. In this paper, we report our results
of preparing the polyacenoquinone derivatives 2D-5D by
benzoannulation of 1,4-quinones 2-5 based on a Diels-Alder
cycloaddition-fragmentation approach using cyclic diene 1
as benzoannulating agent (Scheme I). In most cases, the prep-
aration consists of only two operations with a mild reaction
condition for the one-pot, tandem enolization-oxidation-
fragmentation (2A-5A®2D-5D) using triethylamine to pro-
As reported, cycloadduct 2A could be aromatized with
NaOH in methanol10a or over silica gel10b to give the corre-
sponding hydroquinone 2B. In our hands, however, applica-
tion of the latter method to enolize cycloadducts 3A-5A was
either sluggish or totally ineffective.13 Thus, an effort was
taken to find an appropriate base for enolization, which could
be both effective in the reactions performed at room tempera-
ture and also not destructive to the resulting products. The ef-
fort led us to perform the enolization reactions in dichloro-
methane at room temperature by using triethylamine as a pro-
moter. In the reactions of cycloadducts 2A and 5A, the corre-
sponding annulated hydroquinones 2B and 5B thus formed
were stable and isolatable. Their identity was indicated by the
disappearance of enone groups and the presence of phenolic
hydroxyl groups via infrared, 1H and 13C NMR spectral anal-
yses. Without purification, hydroquinones 2B and 5B were
subsequently subjected to oxidation with 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ), thereby resulting in the
formation of fragmented products 2D and 5D, respectively.
However, in cases of the enolization of cycloadducts 3A and
4A, the reactions produced directly the corresponding poly-
acenoquinone esters 3D and 4D. Apparently, the hydroqui-

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Benzoannulation of Quinones
J. Chin. Chem. Soc., Vol. 51, No. 1, 2004 169
Table 1. Diels-Alder Cycloadditions of 1,4-Quinones 2-5 with 1,2,3,4-Tetrachloro-5,5-
dimethoxycyclopentadiene (1)
O
Cl
Cl
O
OCH3
O
OCH3
Cl
H3CO
Cl
Cl
H3CO
+
PhCH3
reflux
Cl
Cl
Cl
O
1
Entry
1
Dienophile
Cycloadduct
Yielda
77%
Cl
O
OCH3
O
Cl
H3CO
2A
2
Cl
Cl
O
Cl
Cl
H3CO
OCH3
O
3A
4A
2
3
4
3
4
5
82%
92%
73%
Cl
Cl
O
Cl
Cl
H3CO
OCH3
Cl
Cl
O
Cl
O
Cl
H3CO
CN
CN
OCH3
5A
Cl
Cl
O
a Isolated yields after recrystallization from chloroform.
nones 3B and 4B thereby formed in the reactions were rapidly
oxidized by air to the unstable annulated 1,4-quinones, which
subsequently underwent Grob-type fragmentation to afford
3D and 4D. Attempts of isolating hydroquinones 3B and 4B
(or 3C and 4C) from the reactions performed under N2 atmo-
sphere were not successful. Table 2 summarizes the results of
the triethylamine-promoted fragmentation of cycloadducts
2A-5A to form polyacenoquinones 2D and 5D.
moted fragmentation reaction of the corresponding unsym-
metrical cycloadduct 6A (Scheme II). To this end, a solution
of cyclic diene 1 and 2D in toluene was heated under reflux
for 4 days and the corresponding Diels-Alder cycloadduct 6A
was obtained in 86% yield after recrystallization from chlo-
roform. The 1H NMR spectrum displays three singlets for the
Scheme II
The structure of known anthraquinone ester 3D was
suggested by similar mp and the infrared (IR) spectral ab-
sorptions as those reported9 and further supported by addi-
tional spectral analysis (1H and 13C NMR, and MS). The
structures of polyacenoquinone esters 2D, 4D, and 5D were
Cl
O
Cl
O
Cl
Cl
Cl
Cl
Cl
1
H3CO
OCH3
Cl
PhCH3,
reflux, 4 d
Cl
Cl
O
O
H3CO
O
H3CO
O
1
established by spectral analysis (IR, H and 13C NMR, and
86%
2D
6A
MS) and supported by elemental analysis. All the fragmenta-
NEt3, CH2Cl2
air, r.t., 2 h
1
tion products 2D-5D show one singlet at d ~ 4.10 in the H
NMR spectra and two signals at d ~ 165.0 and 53.0 in the 13
C
O
OCH3
Cl
NMR spectra, which together are assignable to the methoxy-
carbonyl group.
Cl
O
O
Cl
O
O
Cl
Cl
Cl
Cl
+
The unsymmetrical naphthoquinone ester 2D has per-
mitted us to extend the investigation of the current approach
for synthesizing bis-methoxycarbonyl substituted anthra-
quinone and the regioselectivity in the triethylamine-pro-
Cl
Cl
Cl
Cl
Cl
70%
O
H3CO
O
O
H3CO
OCH3
(~8 : 1)
6Db
6Da

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170 J. Chin. Chem. Soc., Vol. 51, No. 1, 2004
Chou et al.
Table 2. Base-Promoted Fragmentation of Diels-Alder Cycloadducts 2A-5A to
Benzoannulated Quinones 2D-5D
Cl
O
Cl
O
Cl
Cl
1. Et3N/CH2Cl2
2. [O]
H3CO
OCH3
Cl
Cl
O
Cl
O
H3CO
O
2A-5A
2D-5D
Entry
1
Cycloadduct
Fragmentation Product
Yielda
56%
Cl
O
Cl OH
OCH3
Cl
Cl
H3CO
2A
Cl
Cl
O
2Db
Cl OH
H3CO
O
2B
(80%)
Cl
O
O
Cl
2
3
4
3A
4A
5A
78%
81%
61%
Cl
3D
H3CO
O
Cl
O
O
Cl
Cl
H3CO
O
4D
Cl
O
O
Cl OH
OCH3
Cl
CN
Cl
H3CO
Cl
CN
CN
CN
Cl
5Db
Cl OH
H3CO
O
5B
(71%)
a Total isolated yields after recrystallization from chloroform. Yields were not optimized.
b Obtained by oxidation of the corresponding hydroquinone (2B/5B) with DDQ.
three chemically nonequivalent methoxyl groups, and the 13
C
tallization, was found to be isomeric to 6Da by the similarity
of spectral data. It is impossible to differentiate between
these two isomers by 1H NMR, IR, and MS spectral analyses,
all of which are in harmony with the structures of 6Da and
6Db. However, one of the molecular structures of these two
diester products (6Da) has a mirror-plane of symmetry (s),
perpendicular to the ring framework through the two car-
bonyl groups of the central benzoquione moiety, and the
other structure (6Db) a center of symmetry (i). The major iso-
meric product, which shows a ten-line 13C NMR spectrum
containing two carbon absorptions at d 178.6 and 178.3 at-
tributed to these two carbonyl groups, could only be in agree-
NMR spectrum has 19 lines indicating the expected dissym-
metric property of 6A. When a solution of cycloadduct 6A in
dichloromethane was treated with triethylamine for 2 h, the
reaction produced two fragmented products 6Da and 6Db in
about 8:1 ratio as indicated by the intensity of two (and only
two) singlets in the 1H NMR spectrum of crude product mix-
ture. The major product 6Da, which could be easily separated
and purified by recrystallization from chloroform, had an ele-
mental analysis in accordance with the molecular formula
C18H6Cl6O6. The minor product 6Db, which could only be
obtained in the spectrum-pure form by repetitive recrys-