Cyclization of 1-hydroxy-2-(oxoalkynyl)anthraquinones

Article abstract of DOI:10.1007/s11172-005-0193-8

Procedures were developed for the heterocyclization of 2-benzoylethynyl-1- hydroxy-and 1-hydroxy-2-(1-oxo-3-phenylpropynyl)anthraquinone. The regioselective preparation of 2-substituted anthra[1,2-b]pyran-4,7,12-triones was demonstrated to be possible und

Full text of DOI:10.1007/s11172-005-0193-8

2798
Russian Chemical Bulletin, International Edition, Vol. 53, No. 12, pp. 2798—2804, December, 2004
Cyclization of 1ꢀhydroxyꢀ2ꢀ(oxoalkynyl)anthraquinones
M. A. Mzhelskaya,a I. D. Ivanchikova,a N. E. Polyakov,a A. A. Moroz,b and M. S. Shvartsberga
ꢀ
aInstitute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences,
3 ul. Institutskaya, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 3) 30 7350. Eꢀmail: shvarts@ns.kinetics.nsc.ru
bKemerovo State University,
6 ul. Krasnaya, 650099 Kemerovo, Russian Federation
Procedures were developed for the heterocyclization of 2ꢀbenzoylethynylꢀ1ꢀhydroxyꢀ and
1ꢀhydroxyꢀ2ꢀ(1ꢀoxoꢀ3ꢀphenylpropynyl)anthraquinone. The regioselective preparation of
2ꢀsubstituted anthra[1,2ꢀb]pyranꢀ4,7,12ꢀtriones was demonstrated to be possible under mild
conditions.
Key words: anthraquinones, anthra[1,2ꢀb]pyrantriones, anthra[1,2ꢀb]furandiones, heteroꢀ
cyclization, alkynones, enamines, iodination.
The anthra[1,2ꢀb]pyranꢀ4,7,12ꢀtrione fragment is
in the synthesis of kidamycinone methyl ether (aglycone
methyl ether of kidamycin).1,6 The key step of this proꢀ
cess is the formation of the alkenylpyrone ring involving
the adjacent hydroxy and 4ꢀmethylꢀ2,4ꢀhexadienoyl
groups. The corresponding 9,10ꢀdimethoxyanthracene
derivative was cyclized by prolonged heating with SeO2 in
tertꢀamyl alcohol to prepare the dehydrocyclization prodꢀ
uct in a yield of ~30%. More recently, an alternative
synthesis of 2ꢀalkenylanthra[1,2ꢀb]pyranꢀ4,7,12ꢀtriones
starting from acetylenic derivatives of anthraquinone has
been briefly described.7
In the present study, we examined various procedures
for the synthesis of 2ꢀsubstituted anthrapyrantriones within
the framework of the acetylenic approach. The aim was to
search for regioselective and mild methods of cyclization
of acetylenic precursors, which can be used for the synꢀ
thesis of the target anthrapyrantriones containing chemiꢀ
cally labile substituents.
present as a cyclic moiety in antitumor antibiotics of the
kidamycin group and a series of their biologically active
analogs prepared by biochemical methods.1,2 In spite of a
considerable amount of data on the biological properties
of anthrapyran compounds, procedures for their synthesis
have not been sufficiently developed. It should be noted
that general procedures for the construction of the
benzopyrone structure are known3 and can be used for the
synthesis of anthra[1,2ꢀb]pyrantriones.4,5 It is much more
difficult to introduce an unsaturated or another chemiꢀ
cally labile substituent, which is analogous to those present
in kidamycin antibiotics, at position 2 of these compounds.
This strategy of the formation of the pyran ring anguꢀ
larly fused to the anthraquinone moiety should involve
the O atom of the hydroxy group, two C atoms of anꢀ
thraquinone, and three C atoms of the acetylenic subꢀ
stituent. Evidently, it is advantageous to use the 3ꢀ or
1ꢀoxopropynyl group as an active threeꢀcarbon fragment.
Actually, these groups are chemically equivalent to the
βꢀdiketone group, which is prone to interact with the
orthoꢀarranged hydroxy function resulting in the sixꢀmemꢀ
bered ring closure.3 Therefore, 1ꢀhydroxyꢀ2ꢀ(3ꢀoxoꢀ
1ꢀalkynyl)ꢀ or 1ꢀhydroxyꢀ2ꢀ(1ꢀoxoꢀ2ꢀalkynyl)anthraꢀ
quinones can serve as acetylenic precursors of 2ꢀsubstiꢀ
tuted anthra[1,2ꢀb]pyranꢀ4,7,12ꢀtriones (Scheme 1).
To compare different methods of cyclization, we used
accessible 2ꢀbenzoylethynylꢀ1ꢀhydroxyanthraquinone (1)
as a model key acetylenic compound.
Z are amino sugar residues
One of the possible approaches to construct the
2ꢀalkenylanthrapyran structure was used for the first time
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2686—2692, December, 2004.
1066ꢀ5285/04/5312ꢀ2798 © 2004 Springer Science+Business Media, Inc.

Cyclization of anthraquinones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2799
Scheme 1
Ketone 1 was prepared by condensation of 1ꢀbenzoylꢀ
oxyꢀ2ꢀiodoanthraquinone (2) with cuprous benzoylꢀ
acetylide (Scheme 2). The necessity of protecting the hydrꢀ
oxy group stems from the fact that orthoꢀhydroxyacetylenic
aromatic compounds very readily undergo intramolecular
cyclization in the presence of CuI salts to give benzoꢀ
furans.8
1ꢀHydroxyanthraquinone (3) was iodinated with a
mixture of I2 and HIO3 in boiling aqueous dioxane to give
1ꢀhydroxyꢀ2ꢀiodoanthraquinone (4) in 87% yield. The
benzoyl protection was introduced by refluxing hydroxy
iodide 4 with benzoyl chloride in the presence of K2CO3
in acetone, the yield of benzoyl derivative 2 being 96%.
Condensation of iodide 2 with cuprous benzoylacetylide
in refluxing DMF was completed in 1.5 h to give acetyꢀ
lenic ketone 5 in 70% yield. The hydroxy group was alꢀ
most quantitatively deprotected by stirring compound 5
in concentrated H2SO4 for 5 min.
from benzoyloxy derivative 5 without isolation of hydroxy
ketone 1 was 86%.
One of the goals in the development of approaches to
the synthesis of biologically active anthrapyrantriones is
to introduce and retain substituents (in the simplest case,
the hydroxy group) in the terminal benzene ring of the
fused system in the course of construction of the pyran
ring (it is highly probable that the presence of the hydroꢀ
philic hydroxy group affects substantially the biological
activity of the compound9). In this connection, we atꢀ
tempted to extend the method used for the synthesis of
pyrone 6 to its hydroxylated analog, viz., 11ꢀhydroxyꢀ2ꢀ
phenylanthra[1,2ꢀb]pyranꢀ4,7,12ꢀtrione (7).
Regioselective iodination of 1,8ꢀdihydroxyanthraꢀ
quinone (13) was carried out using successively the boron
acetate and acetyl protections of the hydroxy groups10
(Scheme 3).
1ꢀAcetoxyꢀ8ꢀhydroxyanthraquinone (8), which was
prepared in 94% yield, was iodinated with an I2—HIO3
mixture in refluxing aqueous dioxane (see Scheme 2).
The acetoxy group remained virtually intact in the course
of the reaction, and the yield of 8ꢀacetoxyꢀ1ꢀhydroxyꢀ2ꢀ
iodoanthraquinone (9) was 54%. Then 11ꢀhydroxyꢀ2ꢀ
phenylanthra[1,2ꢀb]pyranꢀ4,7,12ꢀtrione (7) was synꢀ
thesized analogously to pyran 6 using simultaneous
The simplest way of transforming model ketone 1 into
2ꢀphenylanthra[1,2ꢀb]pyranꢀ4,7,12ꢀtrione (6) is based on
its cyclization under conditions of hydration at the triple
bond. The cyclization occurs easily on brief heating in
concentrated H2SO4 (70 °C, 30 min). Evidently, the reꢀ
moval of the benzoyl protection can be combined with
the cyclization step. The yield of compound 6 derived
Scheme 2
R = H (1—6), OAc (8—11), OH (7, 12)

2800
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Mzhelskaya et al.
Scheme 3
deacylation of both hydroxy groups in compound 11 (conꢀ
centrated H2SO4, 20 °C, 15 min).
the chemical shift of this proton is most substantially afꢀ
fected by the structure of the heterocycle. The chemical
shifts of other protons of the benzene ring in molecule 6
are virtually identical to those of 14. Evidently, these
characteristic features of the H NMR spectra of quinoꢀ
nes 6 and 14 can be used to establish the structures of
related compounds.
Unfortunately, this method for the construction of the
γꢀpyrone ring is unsuitable for the preparation of comꢀ
pounds, which, like kidamycin antibiotics, contain acidꢀ
sensitive groups. Under alternative conditions, the startꢀ
ing acetylenic ketones containing the triple bond at the
α,β position of the substituent, are more prone to cyclizaꢀ
tion with the closure of the fiveꢀmembered heterocycle
rather than with the sixꢀmembered ring closure. For exꢀ
ample, model ketone 1 readily undergoes cyclization in
the presence of cuprous phenylacetylide already at 20 °C
to give 2ꢀbenzoylanthra[1,2ꢀb]furanꢀ6,11ꢀdione (14) isoꢀ
meric to pyrone 6. As mentioned above, cyclocondensaꢀ
tion of unprotected hydroxy iodide 4 with cuprous
benzoylacetylide afforded the same furan 14 (Scheme 4).
In alkaline media, cyclization is additionally complicated
by the cleavage of the keto acetylenic group.11
The 1H NMR spectrum of anthrafurandione 14 shows
a signal for the proton of the benzoylꢀsubstituted aroꢀ
matic fiveꢀmembered heterocycle at substantially lower
field than the signal for the proton of the phenylꢀsubstiꢀ
tuted pyrone ring observed in the spectrum of isomeric
anthrapyrantrione 6 (∆δ ~0.7). In addition, the signals for
the protons of the benzene ring annelated with the hetꢀ
erocycle are observed in the spectrum of compound 6 at
lower field than those in the spectrum of compound 14
(δ 8.66 and 8.39 compared to δ 8.34 and 8.13). A comꢀ
parison of the spectra of compounds 6, 14, and 7 and
ketones 1, 5, 11, 12, and 15 (Tables 1 and 2) suggests that
the signals at δ 8.66 (pyran 6) and 8.13 (furan 14) belong
to the proton adjacent to the bridgehead position of the
fused benzene—heterocycle system and, consequently,
1
We expected that the transfer of the carbonyl group
from the γ to α position of the substituent in key precurꢀ
sor 1 would facilitate the formation of the pyrone ring and
allow us to perform cyclization under rather mild condiꢀ
tions (see Scheme 1, path B). To test this assumption,
model ketone 1 was isomerized to 1ꢀhydroxyꢀ2ꢀ(1ꢀoxoꢀ
3ꢀphenylpropynyl)anthraquinone (15) (Scheme 5) by the
successive addition of amine, the preparation of iminium
salt 16 by the reaction of POCl3 with adduct 17, and its
alkaline hydrolysis.12
An excess of piperidine was added to ketone 1 (20 °C,
15 min) to prepare aminovinyl ketone 17 in 89% yield.
Heating of adduct 17 with POCl3 in dioxane afforded
iminium salt 16, which was decomposed (without isolaꢀ
tion) with 10% aqueous KOH. The yield of ketone 15
was 40%. It appeared that ketone 15 underwent partial
cyclization to benzylideneanthra[1,2ꢀb]furanꢀ3,6,11ꢀ
trione (18) in the course of the synthesis. This secondary
reaction occurs, apparently, in an alkaline medium in the
course of decomposition of iminium salt 16. Ketone 15
was completely transformed into furanone 18 on heating
in the presence of cuprous phenylacetylide in toluene.
Consequently, the transfer of the carbonyl group in acetyꢀ
lenic ketone does not exclude the possibility of the formaꢀ
tion of the fiveꢀmembered ring. Apparently, the tendency
to the fiveꢀmembered ring closure is retained due, in part,
Scheme 4

Cyclization of anthraquinones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2801
Table 1. Physicochemical properties of acetylenic ketones derived from anthraquinone
Comꢀ
M.p./°C Found
Molecular
formula
1H NMR
(CDCl3, δ, J/Hz)
IR,
ν/cm–1
(%)
pound (benzene— Calculated
hexane)
С
H
1
5
209—211 78.53 3.48
78.40 3.43
С23H12О4
7.45—7.70 (m, 3 H, 3 HPhm,p); 7.80—7.90
1645, 1680
(С=О); 2215
(С≡С)
(m, 3 H, H(4) (H(3)), H(6), H(7)); 8.00 (d, 1 H,
H(3) (H(4)), J = 7.9); 8.25—8.40 (m, 4 H, 2 HPho,
H(5), H(8)); 13.30 (s, 1 H, ОH)
230—231.5 78.73 3.48
78.94 3.58
С30H16О5
7.00—7.15 (m, 2 H, 2 HPhm, ≡ССOPh); 7.35—7.50
(m, 1 H, 1 HPhp, =ССOPh); 7.50—7.65 (m, 1 H,
2 HPhm, ОСOPh); 7.65—7.85 (m, 3 H, H(6), H(7),
1 HPhp, ОСOPh); 7.90—8.00 (m, 2 H, 2 HPho,
≡ССOPh); 8.10—8.25 (m, 1 H, H(5) (H(8))); 8.17 (d,
1 H, H(3) (H(4)), J = 8.1); 8.25—8.30 (m, 1 H,
H(8) (H(5))); 8.30—8.45 (m, 2 H, 2 HPho, ОСOPh);
8.39 (d, 1 H, H(4) (H(3)), J = 8.0)
1645, 1680
(С=О);
1750
(О—С=О);
2220 (С≡С)
11
212—214 74.74 3.40
74.70 3.53
С31H18О7
2.05 (s, 3 H, Me); 7.05—7.15 (m, 2 H, 2 HPhm,
≡ССOPh); 7.40 (dd, 1 H, H(7), J = 8.1, J = 1.3);
7.40—7.50 (m, 1 H, 1 HPhp, ≡ССOPh); 7.55—7.65
(m, 2 H, 2 HPhm, ОСOPh); 7.65—7.75 (m, 1 H,
1 HPhp, OСOPh); 7.79 (t, 1 H, H(6), J = 7.9);
7.95—8.05 (m, 2 H, 2 HPho, ≡ССOPh); 8.12 (d, 1 H,
H(3) (H(4)), J = 8.1); 8.23 (dd, 1 H, H(5), J = 7.8,
J = 1.3); 8.30—8.40 (m, 2 H, 2 HPho, ОСOPh);
8.30 (d, 1 H, H(4) (H(3)), J = 8.1)
1650, 1685
(С=О);
1765
(О—С=О);
2220 (С≡С)
12
15
218—220 75.17 3.18
75.00 3.28
С23H12О5
7.34 (d, 1 H, H(7), J = 7.9); 7.50—7.65 (m, 3 H, 3 HPh);
7.74 (t, 1 H, H(6), J = 7.9); 7.87 (d, 2 H, H(4) (H(3)),
H(5), J = 7.9); 8.01 (d, 1 H, H(3) (H(4)), J = 7.9);
8.25—8.35 (m, 2 H, 2 HPh); 11.92 (s, 1 H, ОH);
12.80 (s, 1 H, ОH)
1640, 1680
(С=О);
2215 (С≡С)
185—1865
—
—
С23H12О4
7.35—7.50 (m, 3 H, 3 HPh); 7.65—7.75 (m, 2 H, 2 HPh); 1650, 1685
7.80—7.90 (m, 2 H, H(6), H(7)); 8.25—8.40 (m, 2 H, H(5), (С=О);
H(8)); 7.91 (d, 1 H, H(4) (H(3)), J = 8.1); 8.46 (d, 1 H,
H(3) (H(4)), J = 8.1); 13.76 (s, 1 H, ОH)
2190 (С≡С)
Table 2. Physicochemical properties of fused heterocyclic anthraquinone derivatives
Comꢀ
pound
M.p./°C Found
(benzene— Calculated
hexane)
Molecular
formula
1H NMR
(CDCl3, δ, J/Hz)
(%)
С
H
6
326—3275
(dichloroꢀ
ethane)
—
—
С23H12О4
С23H12О5
С23H12О4
С23H12О4
7.01 (s, 1 H, H(3)); 7.60—7.70 (m, 3 H, 3 HPh); 7.80—7.90 (m, 2 H, H(9),
H(10)); 8.25—8.40 (m, 4 H, 2 HPh, H(8), H(11));
8.39 (d, 1 H, H(6) (H(5)), J = 8.2);
8.66 (d, 1 H, H(5) (H(6)), J = 8.2)
7
342—344 74.79 3.27
75.00 3.28
7.01 (s, 1 H, H(3)); 7.39 (d, 1 H, H(10), J ≈ 8.2); 7.55—7.65 (m, 3 H,
3 HPh); 7.71 (t, 1 H, H(9), J = 8.0); 7.85 (d, 1 H, H(8), J ≈ 8.0);
8.25—8.35 (m, 2 H, 2 HPh); 8.37 (d, 1 H, H(6) (H(5)), J = 8.2);
8.69 (d, 1 H, H(5) (H(6)), J = 8.2); 12.82 (s, 1 H, ОH)
7.74 (s, 1 H, H(3)); 7.60—7.70 (m, 3 H, 3 HPh); 7.75—7.85 (m, 2 H, H(8),
H(9)); 8.13 (d, 1 H, H(4) (H(5)), J = 8.3);
8.34 (d, 1 H, H(5) (H(4)), J = 8.3);
8.30—8.50 (m, 4 H, 2 HPh, H(7), H(10))
7.07 (s, 1 H, =СH); 7.45—7.65 (m, 3 H, 3 HPh); 7.80—7.90 (m, 2 H,
H(8), H(9)); 8.15—8.40 (m, 6 H, H(4), H(5), H(7), H(10), 2 HPh)
14
18
268—270 78.45 3.51
(dichloroꢀ 78.40 3.43
ethane)
298—300 78.37 3.41
78.40 3.43

2802
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Mzhelskaya et al.
Scheme 5
to the fact that the strongest electrophilic center of the
adjacent substituent, viz., the acetylenic C atom at the
β position with respect to the carbonyl group, is spatially
remote from the O atom of the hydroxy group. Evidently,
the formation of the sixꢀmembered ring requires that this
C atom and the O atom of the hydroxy group be in spatial
proximity. This can readily be achieved by the addition of
secondary amine at the triple bond of compound 15
(Scheme 6).
Actually, adduct 19 gave pyrone 6 upon heating in a
CHCl3—dioxane—water mixture acidified with a small
amount of H2SO4 (method a), i.e., under substantially
milder conditions than those used for cyclization of
2ꢀbenzoylethynylꢀ1ꢀhydroxyanthraquinone (1). Neverꢀ
theless, the possibility of using this procedure for the synꢀ
thesis of anthrapyrantriones containing acidꢀsensitive subꢀ
stituents is in doubt. Baseꢀcatalyzed cyclization of the
adduct leading to the intramolecular nucleophilic substiꢀ
tution of the dialkylamino group holds more promise.13
Another advantage of this procedure is that it allows one
to combine the steps of adduct formation and cyclization.
The reaction of acetylenic ketone 15 was carried out with
the use of more than one equivalent of piperidine in anꢀ
hydrous benzene (method b). At 80 °C, the reaction time
was 1 h; the yield of pyran 6 was 83% (the method a
produced pyran 6 in 51% yield).
During monitoring of the adduct formation and cyꢀ
clization by TLC, we paid attention to instability of
aminovinyl ketone 19 on silica gel and found that it was
transformed into anthrapyran 6 already on the adsorbent.
Scheme 6
Reagents and conditions: a. H2SO4 (cat.)/CHCl3—dioxane—H2O; b. Piperidine, C6H6, 80 °C; c. Silica gel, 20 °C.

Cyclization of anthraquinones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2803
Calculated (%): C, 55.53; H, 2.44; I, 27.94. 1H NMR, δ:
7.55—7.65 (m, 2 H, 2 HPh); 7.65—7.80 (m, 3 H, H(6), H(7),
1 HPh); 8.05 (d, 1 H, H(3), J = 8.3 Hz); 8.10—8.20 (m, 1 H,
H(5) (H(8))); 8.20—8.30 (m, 1 H, H(8) (H(5))); 8.33 (d, 1 H,
H(4), J = 8.3 Hz); 8.25—8.35 (m, 2 H, 2 HPh).
8ꢀAcetoxyꢀ1ꢀbenzoyloxyꢀ2ꢀiodoanthraquinone (10) was preꢀ
pared analogously to compound 2 from 8ꢀacetoxyꢀ1ꢀhydroxyꢀ2ꢀ
iodoanthraquinone (9). After recrystallization from a 1 : 1 benꢀ
zene—hexane mixture, the yield of compound 10 was 79%, m.p.
204—206 °C. Found (%): C, 54.12; H, 2.51; I, 24.75. C23H13IO6.
Calculated (%): C, 53.93; H, 2.56; I, 24.77. 1H NMR, δ: 2.02 (s,
3 H, Me); 7.37 (dd, 1 H, H(7), J = 8.2 Hz, J = 1.3 Hz);
7.50—7.65 (m, 2 H, 2 HPh); 7.65—7.70 (m, 1 H, 1 HPh); 7.75
(t, 1 H, H(6), J = 8.0 Hz); 7.96 (d, 1 H, H(3), J = 8.3 Hz); 8.20
(dd, 1 H, H(5), J = 7.8 Hz, J = 1.3 Hz); 8.30 (d, 1 H, H(4), J =
8.3 Hz); 8.25—8.35 (m, 2 H, 2 HPh).
2ꢀBenzoylethynylꢀ1ꢀbenzoyloxyanthraquinone (5). A mixture
of iodoanthraquinone 2 (4.54 g, 10 mmol) and cuprous benzoylꢀ
acetylide (2.22 g, 11.5 mmol) in DMF (200 mL) was refluxed
with stirring under argon for 1.5 h, filtered, and poured into
CHCl3 (600 mL). The chloroform solution was washed with
water and dried with MgSO4. The solvent was distilled off
in vacuo, and the residue was recrystallized from toluene
(110 mL). The yield of ketone 5 was 3.20 g (70%) (see Table 1).
8ꢀAcetoxyꢀ2ꢀbenzoylethynylꢀ1ꢀbenzoyloxyanthraquinone (11)
was prepared analogously to ketone 5 from iodide 10 (the reacꢀ
tion time was 45 min) in 74% yield (see Table 1).
2ꢀBenzoylethynylꢀ1ꢀhydroxyanthraquinone (1). Benzoyloxyꢀ
anthraquinone 5 (2.40 g, 5.3 mmol) in concentrated H2SO4
(80 mL) was stirred at 20 °C for 5 min, poured into water
(400 mL), and extracted with CHCl3. After removal of the solꢀ
vent in vacuo, the residue was recrystallized from benzene. The
yield of compound 1 was 1.80 g (96%) (see Table 1)
This provided the basis for developing yet another mild
and convenient method of cyclization of adduct 19
(method c). Cyclization occurs once a chloroform soluꢀ
tion of adduct 19 is deposited on the adsorbent, the color
of the adsorbed compound being changed from red to
yellow. The reaction was completed in 2 h; the yield of
anthrapyrantrione 6 was 82%.
Therefore, under particular reaction conditions, model
ketone 1 and its isomer 15 undergo regioselective cyclizaꢀ
tion to form the 2ꢀsubstituted γꢀpyrone ring. It is advantaꢀ
geous to perform the synthesis of anthrapyranoquinones
containing chemically labile substituents at position 2
starting from 2ꢀ(1ꢀoxoalkynꢀ2ꢀyl)anthraquinones 15,
which can undergo cyclization, through piperidine adꢀ
ducts 19 under mild conditions (methods a—c, see
Scheme 6). The efficiency of this approach was supported
by the successful synthesis of 2ꢀalkenylanthra[1,2ꢀb]pyꢀ
ranꢀ4,7,12ꢀtriones.7
Experimental
1
The H NMR spectra were recorded on a Bruker DPXꢀ200
instrument (200 MHz) in CDCl3 at 25 °C. The IR spectra were
measured on a URꢀ20 spectrometer in CHCl3. The course of the
reactions and purity of the reaction products were monitored by
TLC on Silufol UV 254 plates.
1ꢀAcetoxyꢀ8ꢀhydroxyanthraquinone (8) was prepared accordꢀ
ing to a known procedure10 by heating 1,8ꢀdihydroxyanthraꢀ
quinone (13) (4.80 g, 20 mmol) in Ac2O (100 mL) in the presꢀ
ence of H3BO3 (5.00 g, 80 mmol) at 95 °C for 5 h. The yield
of compound 8 was 5.30 g (94%), m.p. 191—192 °C (benꢀ
zene—hexane).
1ꢀHydroxyꢀ2ꢀiodoanthraquinone (4). Iodine (1.12 g,
4.4 mmol) and HIO3 (1.76 g, 10 mmol) in water (20 mL) were
added to a solution of anthraquinone 3 (2.24 g, 10 mmol) in
dioxane (60 mL) at 80 °C. The reaction mixture was refluxed
with stirring for 2.5 h, cooled, and poured into water (300 mL).
The precipitate that formed was filtered off, washed with water,
and dried in air. After recrystallization from dioxane, comꢀ
pound 4 was obtained in a yield of 3.05 g (87%), m.p. 186—187 °C
(benzene—hexane).14
8ꢀAcetoxyꢀ1ꢀhydroxyꢀ2ꢀiodoanthraquinone (9) was syntheꢀ
sized analogously to iodoanthraquinone 4 from 1ꢀacetoxyꢀ8ꢀ
hydroxyanthraquinone (8) (the reaction time was 6 h). The
yield was 54%, m.p. 222—224 °C. Found (%): C, 47.26; H, 2.29;
I, 31.18. C16H9IO5. Calculated (%): C, 47.08; H, 2.22; I, 31.09.
1H NMR, δ: 2.44 (s, 3 H, Me); 7.44 (dd, 1 H, H(7), J = 8.1 Hz,
J = 1.3 Hz); 7.55 (d, 1 H, H(3), J = 8.1 Hz); 7.83 (t, 1 H, H(6),
J = 8.0 Hz); 8.19 (d, 1 H, H(4), J = 8.1 Hz); 8.30 (dd, 1 H,
H(5), J = 7.8 Hz, J = 1.3 Hz); 13.48 (s, 1 H, OH).
2ꢀBenzoylethynylꢀ1,8ꢀdihydroxyanthraquinone (12). Diacylꢀ
anthraquinone 11 was deacylated as described above for benzoyl
derivative 5 (the reaction time was 15 min). Product 12 was
purified by chromatography on SiO2 using CHCl3 as the eluent;
the yield was 71% (see Table 1).
1ꢀHydroxyꢀ2ꢀ(3ꢀoxoꢀ1ꢀpiperidinoꢀ3ꢀphenylpropenyl)anthraꢀ
quinone (17). A solution of ketone 1 (1.40 g, 4.0 mmol) in piperiꢀ
dine (50 mL) was stirred at 20 °C for 15 min. The reaction
mixture was diluted with CHCl3 (300 mL), washed with water,
and dried with MgSO4. The solvent was removed in vacuo. Reꢀ
crystallization from a 1 : 1 benzene—hexane mixture afꢀ
forded aminovinyl ketone 17 in a yield of 1.55 g (89%), m.p.
209—211 °C. Found (%): C, 76.68; H, 5.19; N, 3.04.
C
28H23NO4. Calculated (%): C, 76.87; H, 5.30; N, 3.20.
1H NMR, δ: 1.65 (br.s, 6 H, βꢀ and γꢀCH2); 3.38 (br.s, 4 H,
NCH2); 6.16 (s, 1 H, =CH); 7.30—7.40 (m, 3 H, 3 HPh);
7.53 (d, 1 H, H(3), J = 8.0 Hz); 7.88 (d, 1 H, H(4), J =
8.0 Hz); 7.75—7.85 (m, 4 H, 2 HPh, H(6), H(7)); 8.25—8.35
(m, 2 H, H(5), H(8)); 12.99 (s, 1 H, OH). IR, ν/cm–1: 1645,
1680 (C=O).
1ꢀBenzoyloxyꢀ2ꢀiodoanthraquinone (2). A mixture of 1ꢀhydrꢀ
oxyꢀ2ꢀiodoanthraquinone (4) (6.00 g, 17 mmol), benzoyl chloꢀ
ride (4.80 g, 34 mmol), and a K2CO3 powder (30.00 g, 220 mmol)
in dry acetone (420 mL) was refluxed for 25 min and then
filtered. Water (500 mL) was added to the filtrate. The precipiꢀ
tate that formed was separated, washed with water, and dried.
The yield of benzoyl derivative 2 was 7.50 g (97%), m.p.
206—207 °C. Found (%): C, 55.65; H, 2.40; I, 28.00. C21H11IO4.
1ꢀHydroxyꢀ2ꢀ(1ꢀoxoꢀ3ꢀphenylpropynyl)anthraquinone (15).
A mixture of compound 17 (0.22 g, 0.5 mmol) and POCl3 (0.15 g,
1 mmol) in dioxane (7 mL) was heated at 80 °C for 80 min,
poured into a 10% aqueous KOH solution (10 mL), stirred for
10 min, diluted with water (100 mL), and extracted with CHCl3.
After removal of the solvent, the residue (0.10 g) containing two
compounds (TLC data) was twice recrystallized from a 1 : 2
benzene—hexane mixture, and ketone 15 was isolated in a yield

2804
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Mzhelskaya et al.
of 70 mg (40%) (see Table 1). The second compound present in
the crude product was identified as anthrafurantrione 18.
2ꢀBenzylideneanthra[1,2ꢀb]furanꢀ3,6,11ꢀtrione (18). A mixꢀ
ture of ketone 15 (75 mg, 0.2 mmol) and cuprous phenylacetylide
(66 mg, 0.4 mmol) in anhydrous toluene (20 mL) was heated
under argon at 90 °C for 4 h, filtered, concentrated in vacuo
until crystallization started, and then cooled. Crystals of furanone
18 were filtered off. The yield of compound 18 was 45 mg (60%)
(see Table 2).
(100 cm3, 40—100 µm). After 2 h, pyran 6 was eluted with
CHCl3; the yield was 0.14 g (82%).
11ꢀHydroxyꢀ2ꢀphenylanthra[1,2ꢀb]pyranꢀ4,7,12ꢀtrione (7).
Cyclization of 8ꢀacetoxyꢀ2ꢀbenzoylethynylꢀ1ꢀbenzoyloxyꢀ
anthraquinone (11) (0.26 g, 0.5 mmol) was carried out analoꢀ
gously to compound 5 in concentrated H2SO4 (20 mL) at 80 °C
for 1.5 h. Chromatography of the crude product on SiO2 in
CHCl3 afforded hydroxypyran 7 in a yield of 0.13 g (71%) (see
Table 2).
2ꢀBenzoylanthra[1,2ꢀb]furanꢀ6,11ꢀdione (14). A. A mixture
of ketone 1 (110 mg, 0.3 mmol) and cuprous phenylacetylide
(50 mg, 0.3 mmol) in pyridine (10 mL) was stirred under argon
at 20 °C for 0.5 h, diluted with CHCl3 (100 mL), and washed
with dilute HCl and water. After removal of CHCl3, the residue
was recrystallized from dichloroethane. Furan 14 was obtained
in a yield of 72 mg (68%) (see Table 2).
B. A mixture of iodide 4 (0.41 g, 1.15 mmol) and cuprous
benzoylacetylide (0.22 g, 1.15 mmol) in DMF (30 mL) was
refluxed with stirring under argon for 1.5 h, filtered, diluted with
CHCl3 (200 mL), and washed with water. The solvent was reꢀ
moved in vacuo. The residue was recrystallized from dichloroꢀ
ethane. Furan 14 was obtained in a yield of 0.26 g (73%).
2ꢀPhenylanthra[1,2ꢀb]pyranꢀ4,7,12ꢀtrione (6). A. 2ꢀBenzoylꢀ
ethynylꢀ1ꢀbenzoyloxyanthraquinone (5) (114 mg, 0.25 mmol)
in concentrated H2SO4 (5 mL) was stirred at 70 °C for 0.5 h,
poured into water (200 mL), and extracted with CHCl3 (300 mL).
Pyran 6 was obtained in a yield of 78 mg (89%) (see Table 2).
Under the same conditions, pyran 6 was prepared from
2ꢀbenzoylethynylꢀ1ꢀhydroxyanthraquinone (1) in 89% yield.
References
1. F. M. Hauser and R. P. Rhee, J. Am. Chem. Soc., 1979,
101, 1628.
2. Jpn Pat. 61/224992; Chem. Abstr., 1987, 106, 137013h.
3. Comprehensive Organic Chemistry, Eds D. Barton and W. D.
Ollis, Pergamon Press, Oxford, 1979, 4.
4. H. Uno, K. Sakamoto, E. Honda, K. Fukuhara, N. Ono,
J. Tanaka, and M. Sakanaka, J. Chem. Soc., Perkin Trans. 1,
2001, 229.
5. K. Krohn and J. Vitz, Eur. J. Org. Chem., 2004, 209.
6. F. M. Hauser and R. P. Rhee, J. Org. Chem., 1980, 45, 3061.
7. M. A. Mzhelskaya, A. A. Moroz, and M. S. Shvartsberg, Izv.
Akad. Nauk SSSR, Ser. Khim., 1991, 1656 [Bull. Acad. Sci.
USSR, Div. Chem. Sci., 1991, 40, 1469 (Engl. Transl.)].
8. C. E. Castro, E. J. Gaughan, and D. C. Owsley, J. Org.
Chem., 1966, 31, 4071.
9. K. Nakamura, T. Asai, T. Hara, N. Minorikawa, and
T. Suami, Bull. Chem. Soc. Jpn, 1983, 56, 1812.
10. R. A. Murphy and M. P. Cava, Tetrahedron Lett., 1984,
25, 803.
11. L. G. Fedenok and M. S. Shvartsberg, Izv. Akad. Nauk
SSSR, Ser. Khim., 1990, 2622 [Bull. Acad. Sci. USSR, Div.
Chem. Sci., 1990, 39, 2376 (Engl. Transl.)].
12. M. S. Shvartsberg and L. G. Fedenok, Izv. Akad. Nauk
SSSR, Ser. Khim., 1990, 2094 [Bull. Acad. Sci. USSR, Div.
Chem. Sci., 1990, 39, 1906 (Engl. Transl.)].
13. S. P. Korshunov, N. V. Korzhova, V. M. Kazantseva, V. L.
Krasnov, N. V. Utekhina, and I. V. Bodrikov, Zh. Org. Khim.,
1986, 22, 1847 [J. Org. Chem. USSR, 1986, 22 (Engl.
Transl.)].
B.
A solution of 1ꢀhydroxyꢀ2ꢀ(1ꢀoxoꢀ3ꢀphenylpropꢀ
ynyl)anthraquinone (15) (105 mg, 0.3 mmol) in piperidine
(5 mL) was stirred at 20 °C for 0.5 h, diluted with CHCl3
(100 mL), and washed with water. The resulting chloroform
solution of adduct 19 was concentrated in vacuo to ~3 mL. Then
dioxane (15 mL) and water (1 mL), which was acidified with
one drop of concentrated H2SO4, were added to the reaction
mixture. The mixture was stirred at 80 °C for 45 min, cooled,
diluted with CHCl3 (100 mL), washed with water, and dried
with MgSO4. Recrystallization from toluene afforded pyran 6 in
a yield of 54 mg (51%).
C. A mixture of ketone 15 (0.18 g, 0.5 mmol) and piperidine
(0.3 mL, 0.30 g, 3 mmol) in anhydrous benzene (10 mL) was
refluxed with stirring for 1 h. After cooling, the precipitate was
filtered off, washed with hexane, and chromatographed on SiO2
in CHCl3. Pyran 6 was obtained in a yield of 0.15 g (83%).
D. A solution of ketone 15 (0.17 g, 0.5 mmol) in piperidine
(5 mL) was stirred at 20 °C for 0.5 h, diluted with CHCl3
(150 mL), and washed with water. The chloroform solution of
adduct 19 was concentrated to ~60 mL and deposited onto SiO2
14. T. P. Galevskaya, A. A. Moroz, R. N. Myasnikova, and
M. S. Shvartsberg, Zh. Org. Khim., 1988, 24, 405 [J. Org.
Chem. USSR, 1988, 24 (Engl. Transl.)].
Received April 22, 2004;
in revised form October 6, 2004